Poster

#8

Immune checkpoint inhibitors and metabolic-endocrine disorders in the US FDA adverse event reporting system: Preliminary results

G. Prada Ramallal¹, L. Romero ² and R. Nogueiras Álvarez³

¹Clinical University Hospital of Santiago, A Coruña, Spain; ²Technical Secretariat of the Medical Research Ethics Committee of Galicia (CEImG), Spain; ³University Hospital Galdakao-Usansolo, Vizcaya, Spain

Objective: Immune checkpoint inhibitors (ICIs) have gained importance in cancer treatment because of their potential to contribute to long-term remission and cure. Although the benefits outweigh the risks, potential serious side effects must be considered, such as immune-related metabolic-endocrine adverse events (AEs). These AEs may correlate with increased progression-free survival and overall survival in ICIs; however, their role as predictive biomarkers is underexplored. Our study aimed to characterize the spectrum, frequency and clinical characteristics of immune-related metabolic-endocrine AEs, as well as other non-specific AEs, associated with ICIs and reported to the FDA Adverse Event Reporting System (FAERS).

Material and/or methods: Data were collected from the FAERS database covering the period from the first quarter of 2012 to the fourth quarter of 2023. The definition relied on System Organ Class and Preferred Terms by the Medical Dictionary for Regulatory Activities (MedDRA). A preliminary descriptive analysis was then performed using R software (version 4.2.3). A Sankey diagram was built with the networkD3 package.

Results: The total number of AEs in FAERS related to the selected drugs was 209 065. AEs were more common in men (53.9%) than women (34.8%). People over 65 years of age account for 40.1% of total AEs. Endocrine disorders represented 8.0% with 16 665 results. Metabolic disorders represented 9.6% with 19 983 results. The most common endocrine AEs were hypothyroidism (27.4%), adrenal insufficiency (18.6%) and hypophysitis (12.7%). The most common metabolic AEs were decreased appetite (27.9%), dehydration (12.6%) and hyponatremia (10.8%). These findings align with previous studies.

Conclusions: This study explores the incidence of metabolic-endocrine AEs associated with ICIs treatment. The results show particularly high rates among older people and men. These findings provide a reliable basis for further comprehensive AEs' investigations. To establish reliable biomarkers for predicting the effectiveness of anti-tumour treatment, additional research and advanced statistical analyses are necessary.

#10

Safety of defibrotide in the prevention and treatment of acute respiratory distress syndrome in patients with COVID-19

P. Rodríguez-Fortúnez¹, A. J. Martínez-Mellado², R. Jara-Rubio², P. Castro-Rebollo³, A. Carrillo-Alcaraz⁴, C. Rodríguez-Jiménez¹, A. Pareja², J. Kiwitt-Cárdenas², A. Torres² and J. M. Moraleda²

¹Clinical Trials Unit, University Hospital of the Canary Islands, Tenerife, Spain; ²University Clinical Hospital Virgen de la Arrixaca, IMIB Pascual Parrilla, University of Murcia, Murcia, Spain; ³Clínic Hospital, Barcelona, Spain; ⁴University Hospital Morales Meseguer, Murcia, Spain

Objective: To evaluate the safety of intravenous infusion of defibrotide (DF) in the prevention and treatment of acute respiratory distress and cytokine release syndrome in patients with SARS-CoV-2 infection.

Material and/or methods: Prospective, multicentre, randomized, double-blind, placebo-controlled, phase IIb clinical trial (CT). DF was infused as a 24-h continuous intravenous infusion in 150 patients and intermittently every 6 h in the last six patients, at a total dose of 25 mg/kg/day for 15 days. EudraCT No: 2020-001409-21.

Results: One hundred fifty-six patients were recruited between April 2020 and July 2022. The mean age of the series was 60 years (range: 34–89 years), being 77% of them male. Out of 156 patients, 116 (74%) were grade 4–5, and 42 (26%) were grade 6 of the scale of seven grades of the WHO.

We collected 825 adverse events (AE), 59 (7.15%) were considered serious adverse events (SAEs), and the 40 patients (42 SAEs) who experienced them died.

The reported SAEs were 59 (56 patients) and are summarized as follows: elevated fibrin D-dimer (three SAEs), elevated transaminase (one SAE), necrotizing pneumonia (one SAE), mechanical ventilation (eight SAEs), interruption of treatment (one SAE), chest drainage (one SAE), thrombosis (nine SAEs), haemorrhage (one SAE), distributive shock (two SAEs), cardiorespiratory arrest (four SAEs), atrial fibrillation (one SAE), pulseless electrical activity (one SAE), arrhythmia (one SAE), tachycardia (one SAE), decreased level of consciousness (one SAE), tonic seizure (one SAE), coma (one SAE), perforation (one SAE), multi-organ dysfunction syndrome (nine SAEs), respiratory failure (six SAEs) and hypoxia (five SAEs).

Only one SAE was considered related to the investigational product (haemorrhage), although it was interpreted as an expected adverse reaction.

Regarding efficacy, we did not find any significant differences among the groups.

Conclusions: There is no evidence of relevant safety risks associated with the use of defibrotide in intravenous infusion in patients with COVID-19.

#11

Safety of the new tacrolimus once-daily dose LCTP (Envarsus®) formulation to prevent post-kidney transplant diabetes in at-risk patients: A randomized, controlled, open-label pilot study

P. Rodríguez-Fortúnez¹, C. Rodríguez-Jiménez¹, E. Pérez-Carreño¹, P. Masiero-Aparicio¹, L. Díaz-Martínez², C. Rodríguez-Adanero², D. Marrero², A. Rodríguez², E. De Bonis-Redondo² and A. Torres-Ramírez³

¹Clinical Trials Unit. Pharmacology Service, University Hospital of the Canary Islands. Spanish Clinical Research Network (SCReN), Tenerife, Spain; ²Nephrology Service, University Hospital of the Canary Islands, Tenerife, Spain; ³Nephrology Service, University Hospital of the Canary Islands. La Laguna University, Tenerife, Spain

Objective: To investigate the safety profile of extended-release tacrolimus formulation Envarsus® compared to the standard tacrolimus formulation Prograf® in patients at high risk of post-transplant diabetes.

Material and/or methods: Randomized, open-label, phase IV, controlled, two-arm clinical trial. EudraCT No: 2017-000718-52.

Results: Sixty-two kidney post-transplant patients were recruited between June 2017 and April 2022. They were randomized in two parallel arms: Arm 1 (Prograf®): 30 patients (mean age: 65 years old, 63% male) versus Arm 2 (Envarsus®): 32 patients (mean age: 64 years old, 76% male).

Seventy-six SAEs have been reported (35 in the Envarsus arm and 41 in the Prograf arm) with no statistically significant differences between arms. Of these 76 SAEs, 25 SAEs were considered serious and expected adverse reactions (32.89%), as they showed a causal relationship with the investigational drugs.

No statistically significant differences in terms of occurrence of total adverse events or total serious adverse events have been detected with the use of Envarsus® versus Prograf® in renal transplant patients.

The number of infectious processes overall was significantly higher in the Prograf® arm than in the Envarsus® arm (28 patients vs. 17, p = 0.03) and in the stratified analysis by sex, it is shown that these differences only occurred in women (12 vs. 4, p = 0.02), not in men. The number of urinary tract infections was significantly higher in the Prograf® arm only in women (9 women vs. 2, p = 0.03).

Finally, the proportion of patients with clinically relevant wound collections (lymphocele, haematoma) was also higher in the Prograf® arm (8 patients vs. 2, p = 0.03). In the stratified analysis by sex, it is shown that these differences existed for men, not for women (7 men vs. 1, p = 0.01).

Conclusions: No relevant differences in terms of pharmacological safety have been found in the use of Envarsus® versus Prograf® in patients after kidney transplantation.

#12

Fulminant myocarditis with myositis after treatment with immune checkpoint inhibitors

K. Vargas-Osorio¹, G. Prada Ramallal¹, T. González-Ferrero² and J.M. Cameselle-Teijeiro^1,3,4

¹Pathology Service, Clinical University Hospital of Santiago, A Coruña, Spain; ²Cardiology Service, University Hospital Lucus Augusti, Lugo, Spain; ³Health Research Institute of Santiago de Compostela (IDIS), A Coruña, Spain; ⁴Department of Pathology, University of Santiago de Compostela, A Coruña, Spain

Objective: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and achieved unprecedented efficacy. However, despite their excellent therapeutic effect, these drugs often cause a wide spectrum of toxicity reactions and immune-related adverse events (IrAEs). Although cardiotoxicity is rare, it has a high mortality and has not been well recognized. This paper aims to highlight the importance of research on IrAEs.

Material and/or methods: Clinical case. Seventy-year-old male with clear cell renal cell carcinoma and metabolic comorbidities treated with radical surgery and adjuvant chemotherapy with ICIs: ipilimumab and nivolumab.

Results: One week after receiving the first dose of immunotherapy, the patient was admitted to the hospital for atypical chest pain with respiratory failure, heart rhythm disturbances (left bundle branch alternans block followed by complete atrioventricular block) and myasthenic syndrome. Despite intensive treatment, the patient's condition deteriorated, leading to multiple organ failure and death within 48 h of admission. A postmortem study was requested from the Pathology Service.

Diagnosis: Myocarditis, myositis and thyroiditis related to treatment with ICIs.

Histologically, an intense diffuse lymphohistiocytic inflammatory infiltrate (positive for CD45, CD3, CD4, CD8 and CD68) was observed, with interstitial oedema and foci of cell necrosis in myocardium, skeletal muscle and thyroid gland, in response to aberrant activation of the immune system secondary to treatment with ipilimumab and nivolumab.

Conclusions: The frequency of grade 3/4 adverse events has been reported to be substantially higher in patients treated with an anti-CTLA/anti-PDL1 combination than in those receiving anti-PDL1 monotherapy (54% vs. 20%). Myocarditis with myositis and rhabdomyolysis is a rare and unpredictable, but clinically significant complication with a high mortality rate. Endomyocardial biopsy is considered the gold standard diagnostic test for inflammatory cardiomyopathy and is an essential tool for ICI-related myocarditis. More studies are needed, especially to understand the genomic correlates of the response, to know who is at risk of developing IrAEs.

#13

Serious skin-related adverse reactions: A review in a Spanish regional pharmacovigilance centre

R. Nogueiras Álvarez¹, R. Arandia Jiménez De Aberasturi¹, A. Salcedo Gallego¹ and M. García García^1,2

¹Osakidetza Basque Health Service, Galdakao-Usansolo University Hospital, Basque Country Pharmacovigilance Unit, Galdakao, Spain; ²Biobizkaia Health Research Institute, Galdakao, Spain

Objective: To identify the most commonly reported serious skin-related adverse drug reactions (ADRs) over the last 5 years in a Regional Centre for Pharmacovigilance in Spain.

Material and/or methods: Suspected cases of serious ADRs from healthcare professionals and citizens received between 01.01.2019 and 31.12.2023 were reviewed. Those related to vaccines were excluded. The following characteristics were collected: demographics, ADRs profile and suspected drugs involved.

Results: Over the study period, 428 cases involving 469 suspected serious skin and subcutaneous tissue-related ADRs were received. Reporting in 2019 accounted for 71 cases versus 135 cases in 2023. Fifty-four per cent were women and most of the cases were in adults and people over 65 years of age (94%).

Among the 469 ADRs, the most frequent were pruritus (19.0%), angio-oedema (14.3%), urticaria (13.2%), erythema (10.0%) and rash (8.5%). In terms of severity, outstanding were DRESS (eight cases that resolved after drug withdrawal), Stevens–Johnson syndrome (two cases) and toxic epidermal necrolysis (two cases, one of which was a progression of a fatal Stevens–Johnson).

From 485 suspected drugs, the most frequent ATC subgroups were: antibacterials for systemic use (J01, n = 77, 15.9%), contrast media (V08, n = 53, 10.9%), agents acting on the renin–angiotensin system (C09, n = 54, 11.1%), immunosuppressants (L04, n = 51, 10.5%), antineoplastic agents (L01, n = 50, 10.3%), analgesics (N02, n = 34, 7.0%), anti-inflammatory and antirheumatic products (M01, n = 18, 3.7%).

In terms of prior knowledge 380 cases (88.8%) involved well-known ADRs, 41 (9.6%) involved unknown ADRs, and 7 (1.6%) had occasional references.

Conclusions: Our study shows an increase in notifications of 90% for serious skin ADRs during the evaluated period. The most reported drugs are systemic antibacterials. Although pruritus is the most reported ADR, it is a symptom that acts as a companion to other ADRs that define case severity. Most of the ADRs reported are well known.

#14

Hypertension and IL-17 inhibitors. A pharmacovigilance study in EudraVigilance

M. García García^1,2, R. Arandia Jiménez De Aberasturi¹, A. Salcedo Gallego¹ and R. Nogueiras Álvarez¹

¹Osakidetza Basque Health Service, Galdakao-Usansolo University Hospital, Basque Country Pharmacovigilance Unit, Galdakao, Spain; ²Biobizkaia Health Research Institute, Galdakao, Spain

Objective: Hypertension is not mentioned in the Summary of Product Characteristics of anti-IL-17 drug brands. However, several studies have evaluated the probable influence of these anti-IL-17 drugs (secukinumab, ixekizumab, brodalumab and bimekizumab) on hypertension. In order to validate this possible safety signal, this study uses the European pharmacovigilance database (EudraVigilance) to analyse the potential disproportionality in reported cases of hypertension associated with these drugs.

Material and/or methods: A case–non-case analysis was performed in EudraVigilance to evaluate the association between exposure to anti-IL-17 drugs and hypertension. Cases were defined as patients who had experienced hypertension [MedDRA SMQ ‘Hypertension’ (narrow)] up to 23 May 2024. Non-cases, used as controls, are all reports of adverse drug reactions (ADR) other than the ADR of interest during the same period. Exposure was defined as exposure to the drug of interest (i.e. anti-IL-17 drugs), whether or not it was suspected of causing the ADR. A signal of disproportionate reporting is identified when the following conditions are met: The lower bound of the 95% CI of the ROR is >1, and the number of individual cases is ≥3. Litigation cases were excluded.

Results: During the study period, 29 929 spontaneous cases of ADRs were registered in EudraVigilance for anti-IL-17. Of these, 837 cases were hypertension. Among these cases, 641 (76.6%) were female, and the mean age was 51.1 ± 11.8 years. The pooled ROR for anti-IL-17 was 1.41 (95% CI 1.32–1.51). Among the four drugs, only secukinumab showed disproportionality: secukinumab (ROR 1.92, 95% CI 1.79–2.07), ixekizumab (ROR 0.37, 95% CI 0.28–0.47), brodalumab (ROR 0.97, 95% CI 0.64–1.47) and bimekizumab (ROR 0.49, 95% CI 0.23–1.04).

Conclusions: Our study shows a signal of disproportionate reporting between anti-IL-17 drugs and hypertension. Secukizumab is associated with a significant disproportionality. Well-designed observational studies are needed to confirm these results.

#15

Drug-induced liver injury (DILI) due anakinra in adult-onset Still's disease (AOSD): Two case reports and review

M. J. Cortés Pestana¹, K. C. Amaro Hosey¹ and R. Antonijoan Arbós^1,2

¹Hospital de la Santa Creu i Santa Pau, Barcelona, Spain; ²Centre d'Investigació del Medicament. Institut de Recerca Sant Pau, Barcelona, Spain

Objective: To describe the main characteristics, approach on diagnosis and treatment of DILI related anakinra in AOSD.

Material and/or methods: We present two clinical cases (41-year-old male and 28-year-old female) with a diagnosis of AOSD treated with anakinra and an acute episode of DILI. Related to the cases, we conducted a bibliographic review about the current knowledge on the approach of diagnosis and treatment of AOSD after DILI episode.

Results: The exact mechanism of anakinra-related DILI is unknown. In early phases, it begins as transitory altered liver function with or without signs/symptoms of hepatic disease (specially the first 6 months) that mimics acute viral hepatitis. In published case reports, it frequently appears in young adults, usually self-limited, and resolves within a few weeks (2–8 weeks) after drug withdrawal. Nevertheless, in some cases, progression to acute liver failure (ALF) is described, requiring quick and aggressive treatment (advanced medical life support, high doses of corticosteroids) and/or liver transplantation. Despite that, death is not an unfrequently ending. Restarting anakinra, tocilizumab or canakinumab could be therapeutic options to consider in this setting, especially achieving consensus in a multidisciplinary setting after evaluation of each case individually.

Conclusions: DILI-related anakinra is a rare but severe adverse effect that potentially can cause ALF and death. A high level of suspicion, exclusion of other possible aetiologies and early withdrawal are key points to the adequate approach that will allow an early and accurate management of DILI-related.

#23

A fatal outcome due to a continuous dosage of gentamicin: A case report

G. Ronda Roca¹, B. Ruiz De Antorán¹, E. Montero Hernández², A. San Martin Espinosa³, M. Lobo Palomar¹, J. Porcel Maleno¹, I. Darnaude Ximenez¹ and C. Avendaño Solá¹

¹Department of Clinical Pharmacology, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain; ²Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain; ³Emergency Department, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain

Objective: To describe a case of fatal toxicity due to gentamicin.

Material and/or methods: Case report and literature review.

Results: We present a 92-year-old female patient with a weight of 39 kg, a history of chronic kidney disease (CKD) and chronic heart failure that presented a fatal nephrotoxicity due to a prescription error of gentamicin. 240 mg of gentamicin was prescribed every 12 h for a colonized chronic vascular ulcer. The patient was admitted to the emergency department with nausea and vomits. At her arrival, she presented metabolic acidosis, hyponatremia and hyperkalaemia. A diagnosis of acute tubular necrosis was reached. Even though an adequate treatment was performed, the patient did not present an improvement and passed away a few hours later. In recent years, studies have been conducted to identify therapies that could prevent gentamicin-induced nephrotoxicity. Most of them are non-clinical studies, but clinical evidence is scarce. Already known strategies to prevent nephrotoxicity should be performed like drug level monitorization, ensuring proper hydration and discontinuation of angiotensin-converting enzyme (which was a chronic medication of the patient). The use of another antibiotic family with less renal toxicity and good penetration to soft tissues, for example, quinolones or clindamycin, might have probably been a better choice.

Conclusions: This case of prescription errors with fatal consequences illustrates the importance of following the basic principles of good prescribing, reinforcing the importance of drug individualization treatment and monitoring the treatment outcome. The case may be helpful for younger doctors who never may have seen a continuous dosage of gentamicin and its ominous consequences. Although some strategies exist to prevent and ameliorate gentamicin-induced nephrotoxicity, insufficient human-based evidence exists, and proper clinical trials should be conducted to demonstrate these clinical benefits. Nevertheless, pharmacokinetic monitoring levels of aminoglycosides is a valid strategy that has proved to reduce the nephrotoxicity effect.

#24

Organ-specific immune-mediated reactions to polyethylene glycol and polysorbate excipients: Three case reports

O. Rogozina¹, S. Martín López¹, E. Ramírez García¹, C. Ruiz Fernández², I. Akatbach Bousaid² and M. González Muñoz²

¹Clinical Pharmacology Department, La Paz University Hospital-IdiPAZ, Madrid, Spain; ²Immunology Department, La Paz University Hospital-IdiPAZ, Madrid, Spain

Objective: To describe unusual cases with delayed hypersensitivity to alcohol excipients which were not previously described in the literature.

Material and/or methods: All the cases were referred to the clinical pharmacology department by other specialists after the valid diagnosis was established and drug-related causality was suspected. Causality assessment was conducted using the SEFV algorithm (Aguirre et al., 2016) and updated RUCAM for the hepatitis case (Danan and Teschke, 2016).

The lymphocyte transformation test (LTT) was performed to drugs with a related causality according to algorithms (SEFV score ≥ +4, RUCAM score ≥ +3). Subsequently, we proceeded with LTT for alcohol excipients after identifying inconsistencies between LTT results and clinical manifestations and continued our investigation into the underlying cause of organ damage.

Results: The first patient's case represents the first documented instance of acute pancreatitis related to PS 80 in the literature. In the second case, we suspect that the liver damage was more likely caused by both medications, macrogols and amoxicillin-clavulanate. Lastly, the third case is the first documented instance of acute interstitial nephritis related to PS 80 in the literature. We have summarized the characteristics of the ADR cases and in vitro testing results in Table 1: We would like to add the table, please. But we do not know in what field.

Conclusions: The LTT is a useful tool for helping diagnose drug-related AP and DILI, and it can be used to identify the specific drug or excipient causing the ADR. These cases highlight the importance of considering PEG and polysorbate excipients in the causality diagnosis of ADRs.

#25

Retrospective study for the identification of adverse drug reactions using the international classification of diseases (ICD-10) codes as a method of active pharmacovigilance

M. D. C. Velázquez Perelló¹, C. Boada Fernández Del Campo¹, E. Fernández Quintana², M. García Sánchez-Colomer², C. Rodríguez Jiménez¹, D. Fondevila Batista¹, C. Grillo Grillo¹, L. Rolingson Landaeta¹, J. A. Fernández Rodríguez¹ and E. J. Sanz Álvarez¹

¹Hospital Universitario de Canarias, San Cristóbal De La Laguna, Spain; ²Centro Autonómico de Farmacovigilancia e Información Terapéutica de Canarias, San Cristóbal De La Laguna, Spain

Objective: We wanted to know the efficiency of ICD 10 codes to detect relevant adverse drug reactions (ADR).

Material and/or methods: The current method we use is based on the manual review of all clinical documentation of patients discharged from certain departments. These were selected because they exhaustively record everything related to the admission process.

We compared this method with the same manual review of patients identified with an ICD code from a set previously defined by us. Twenty-one ICD 10 codes were used to identify cases to be reviewed for ADR.

Results: 6706 cases were reviewed during 4 years with the current method, finding 243 ADR cases, of which 143 were serious (3.62% of the cases rendered an ADR, which were serious in the 65.43% of them).

Using the ICD-10-guided method, we reviewed 286 cases during another 4 years, finding 155 ADR cases with 93 serious ADR cases among them (54.20% of the cases rendered an ADR, which were serious in the 60% of them) of the 21 ICD 10 codes, 14 served as a useful tool to detect serious ADRs, with a positive predictive value of 0,34 for the entire set.

Conclusions: The ICD-10-guided method showed greater efficiency than the current method: It identified a slightly lower number of cases of ADR but supposed an enormous reduction in the number of cases that we have to review while maintaining nearly the same percentage of serious ADR cases detected.

#26

Rituximab-induced disseminated intravascular coagulation

G. Ronda Roca¹, E. Martinez De Antonio², C. Payares Herrera¹, A. De Laiglesia Lorenzo², M. Liébana Villela², B. Navarro Matilla², M. Lobo Palomar¹, J. Porcel Maleno¹, I. Darnaude Ximénez¹ and C. Avendaño Solá¹

¹Department of Clinical Pharmacology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain; ²Department of Hematology and Hemotherapy, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain

Objective: Describe a case report of rituximab-disseminated intravascular coagulation (DIC) and a literature review to describe this adverse event.

Material and/or methods: Case report and literature review.

Results: A 65-year-old male with a medical history of epilepsy and splenic marginal zone lymphoma in progression was admitted to the emergency epartment due to fever and generalized tonic–clonic seizures after the first infusion of rituximab. Blood tests 12 h after rituximab infusion showed acute thrombopenia (12.000/μl), increased prothrombin time, hypofibrinogenemia (101 mg/dl) and D-dimer elevation (246.500 ng/ml). The patient was admitted with the diagnosis of DIC-like disorder. Seizures were attributed to treatment non-compliance. Blood abnormalities resolved after 3 days of supportive treatment, and the patient was discharged. A positive re-challenge occurred with the second dose of rituximab, which was stopped due to fever (40°C). The next day the patient presented a mild coagulopathy that resolved with vitamin K.

According to the rituximab summary of product characteristics, coagulation abnormalities are infrequent (≥1/1.000 < 1/100). In the FEDRA database, six cases of coagulopathies due to rituximab were reported, and one was a DIC-like case. A DIC-like case was also reported with obinutuzumab, and no cases were reported concerning ocrelizumab. In the published literature, four case reports of rituximab DIC-like cases were identified, one resulting in death due to bleeding complications. Six additional DIC-like cases were also reported after the first administration of obinituzumab, all subclinical and self-limited.

The biological mechanism of this adverse event is unknown and may be related to cytokine release syndrome and activation of the complement cascade.

The reintroduction of anti-CD20 drugs following DIC-like episodes has not been studied.

Conclusions: DIC-like cases after administration of anti-CD20 agents are infrequent but potentially life-threatening. A careful, individualized benefit–risk assessment is needed if the reintroduction of the suspect medicine is considered in the context of onco-haematological disorders with limited treatment alternatives.

#29

Pharmacoepidemiology of autolytic attempts with drugs

I. Aguado Sempere¹, K. P. Rincón García¹, H. Vera Valero², P. Zapater Hernández^2,1 and A. C. Londoño Ramírez²

¹Hospital General Universitario Dr. Balmis, Alicante, Spain; ²Departamento de Farmacología, Pediatría y Química Orgánica de la Universidad Miguel Hernández, Elche, Spain

Objective: To describe the incidence and characteristics of autolytic attempts with drugs in the health area of HGUDB and to model the magnitude of the problem.

Material and/or methods: Descriptive cross-sectional study with pharmacoepidemiological variables (sex, age, drugs used, autolytic intent, previous attempts, patient outcome) based on the medical records of patients admitted to HGUDB with diagnoses of voluntary overdoses suspected of autolytic intent over 5 months. Data were described as mean and standard deviation (SD) or as frequencies and percentages. Differences were assessed using Student's t-test or Mann–Whitney and chi-square tests. The expected value is estimated from the suicide statistics of the INE (National Statistics Institute).

Results: A total of 131 overdoses were recorded between 3 November 2022 and 27 March 2023. Of these, 68% (89 out of 131) were women. In the child and adolescent population, 15 out of 18 cases were women (83%; p = 0.03). The average age was 38 (17). The most frequent pharmacological groups were (1) benzodiazepines (47%), (2) NSAIDs (16%), (3) paracetamol (10%) and (4) antidepressants (6%). In 21% of cases, multiple drugs were ingested simultaneously. No differences were found between drugs based on sex or age. Seventy-eight per cent of the patients required hospital admission for more than 24 h, and 10 patients (7.6%) were admitted to intensive care. One case resulted in death. The number of observed cases is 4–13 times higher than expected, estimated from the total number of deaths by drug-related suicide in the Valencian Community and the range of fatal suicide rates reported in the literature.

Conclusions: Benzodiazepines are the most commonly used drug group in autolytic attempts, although in one out of every five cases, multiple drugs were ingested simultaneously. The data recorded in our centre show an incidence 4–13 times higher than expected.

#36

Prevalence of immune-related adverse reactions in patients treated with nivolumab at Puerto Real University Hospital

L. Bello Bello, J. B. Raffo Nogueira, M. Fernández-Pujol Marzo, M. E. Pacheco Rodríguez, M. J. Pedrosa Martínez and J. M. Dodero Anillo

Hospital Universitario Puerto Real, Puerto Real, Spain

Objective: To determine the prevalence of immune-related adverse reactions caused by nivolumab in our healthcare area.

Material and/or methods: During the day-to-day practice of notifying adverse drug reactions (ADR) in the clinical pharmacology department, we detected cases of immune-related (IR) ADR due to the recently implemented anti-PD-L1 therapy, most of them associated with nivolumab, both in monotherapy and combination therapy. A review of the available literature provided insights that these IR-ADRs can appear in up to 85% of cases in monotherapy and 78% in combination therapy. Based on these findings, we decided to study the prevalence of reactions in patients receiving nivolumab from 1 January 2022 to 31 December 2023.

Results: In the studied period, we found that 68 patients received at least one dose of nivolumab, 40 of them in monotherapy. Of the total, 25 (36.7%) presented some type of IR-ADR; nine of these were grade 3, and three were grade 4. For all patients who had a G3 or above ADR, the treatment was suspended. Seventeen of these reactions (68%) occurred in monotherapy, with the most common being pneumonitis, with a total of five cases, four of which were G3 or above, followed by hyperthyroidism and interstitial nephritis. The most frequent aetiology associated with IR-ADRs was metastatic melanoma, accounting for 11 of the 21 cases (52.4%), followed by clear cell renal cancer, accounting for six of the 18 cases (33%).

Conclusions: It seems that there is a lower prevalence of IR-ADRs in our healthcare area than the one reported in the literature, with most cases being grade 3 or above and more frequently observed in those treated for melanoma. However, we would need a larger sample and/or a bigger study to achieve better clinical significance.

#41

Preconcepcional and on-pregnancy biological therapy exposure; a case series

Á. Cadenas Manceñido¹, R. C. Álvarez Cabrera¹, R. Ordorica López¹, L. Lavín Alconero¹, N. Vega Gil¹, D. Z. Cuellar Gómez¹, B. Alonso Gómez¹, P. Calvo Pajares¹, I. Mazón Maraña² and M. M. García Saiz¹

¹Hospital Universitario Marqués de Valdecilla, Santander, Spain; ²Servicio Cántabro de Salud, Santander, Spain

Objective: To describe a case series relative to biological therapy use on preconcepcional desire stage and on-pregnancy women. Exposure can be accidental or as part of planificated therapeutic plan.

To present the use of the therapeutic consultation (TC) system and the role of the Clinical Pharmacology Service in clinical decision-making.

To evaluate the in-resulted effects over the fetus by biological drugs and to compare them with previous bibliography.

Material and/or methods: Descriptive observational case series study. Clinical information was extracted from patients' medical records called ‘Altamira’. Information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for medicines and Medical Devices (AEMPS).

Results: TC were classified according to a 13 category system based on their main theme. For the total of 156, only 52 were selected (‘Consultation on teratogenic risk on the pregnancy’ category), meaning a 33.3% of all TC, reflecting that one third of the global work burden of Clinical Pharmacology Service CT system is due to this kind of interconsultartions.

For these 52 cases, only four were relative to biological drugs: rituximab, tocilizumab and secukinumab. Only for rituximab adverse events were described for the fetus; however, none of the babies or embryos presented one.

For three of the four women, the therapeutic decision was keeping the drug line for their diseases, based on the risk-and-benefit balance and teratogenic risk evaluation. None of them experienced any adverse events.

Conclusions: Although there is not enough evidence to fully set the teratogenic risk for certain biological drugs, in this case series, four cases have been presented, and four patients exposed did not present any adverse event, nor their babies, including malformations and spontaneous abortion. Further research is still needed in order to understand the risk of these novel molecules for the pregnancy.

#45

SonoVue® and hypersensitivity risk

J. L. Rolingson Landaeta¹, C. Boada Fernández Del Campo¹, M. Garcia Sanchez-Colomer², E. Fernández Quintana², C. Rodríguez Jiménez¹, D. Fondevilla Batista¹, C. Grillo Grillo¹, C. Velázquez Perelló¹, J. A. Fernandez Rodriguez¹ and E. Sanz Álvarez¹

¹Hospital Universitario de Canarias, La Laguna, Spain; ²Centro Autómico de Farmacovigilancia de Canarias, La Laguna, Spain

Objective: To report the risk of presenting a serious adverse drug reaction (ADR), such as Kounis syndrome or coronary ischaemia phenomena secondary to the use of SonoVue® and its clinical management.

Material and/or methods: This drug is used as an ultrasound enhancer in scans to differentiate solid areas surrounded by liquids. Active ingredient is sulfur hexafluoride in the form of microbubbles, which are broken by the mechanical action of the ultrasonic wave and release the gas.

We reviewed all the cases of this ADR secondary to the use of SonoVue. Causality was assessed using Karch and Lasagna algorithm. Information contained in European and American technical data sheets was analysed. A systematic review of the literature was performed, and the information from the Spanish Adverse Drug Reaction Database (FEDRA) was reviewed.

Results: In a period of 6 months, three cases of severe ADR and one death have been reported (end of 2022 and beginning of 2023). These patients presented hypotension, dyspnoea, sweating, requiring ventilation and aggressive measures.

The data sheets were confusing with regard to safety information. The FEDRA search reports 116 cases of possible ADRs in the last 20 years, mainly in adults with a cardiovascular history like ours. Three serious paediatric cases were associated with off-label use. Several case series studies suggest a very low incidence of serious ADRs associated with the use of this drug. One study showed an incidence of 0.0098%, while another study on 464 266 administrations has calculated an incidence of 1/27324 (0.0036%) for ADRs with a hypersensitivity profile and severe in their form of presentation.

Conclusions: Severe ADRs due to hypersensitivity to SonoVue® are extremely rare but potentially fatal. Close monitoring during and after administration and rapid access to emergency support is crucial. Early identification of symptoms that predict a severe reaction and rapid intervention are essential.

#47

Medication error between scopolamine and butylscopolamine in hospitalized patients: Report of three cases

E. M. Pérez López¹, C. M. Jiménez Martín¹, J. Navarro Roldán¹, N. Merino Kolly², L. M. Rojas Herrera¹, C. Martín Derderian¹, A. Melcón De Dios¹ and P. Máiquez Asuero¹

¹Unidad de Gestión Clínica de Farmacología Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain; ²Centro Andaluz de Farmacovigilancia, Sevilla, Spain

Objective: To describe three cases of erroneous prescription of scopolamine hydrobromide instead of butylscopolamine bromide, emphasizing the importance of reporting medication errors.

Material and/or methods: Two medication errors were identified in two female patients admitted to the hospital, both aged 57 and 68 years, who were administered scopolamine hydrobromide, a pre-anaesthetic medication, instead of butylscopolamine butylbromide for abdominal colic pain, causing serious adverse reactions: dizziness, nausea, confusion, dysarthria, disorientation, hypotension, head trauma and amnesia. Both cases were reported to the Spanish Pharmacovigilance System. In addition, a retrospective search was conducted in the hospital's adverse event reporting system, revealing a case from the previous year with the same prescription error, but without the drug being administered to the patient.

Results: The hospital prescribing system was modified to reduce the risk of confusion between the two active ingredients. On a national level, the Spanish Pharmacovigilance System issued a warning information note highlighting the risks of misprescribing these two medications. Additionally, the name of the active ingredient has been changed in the summary of product characteristics from ‘scopolamine butylbromide’ to ‘butylscopolamine bromide’ to minimize the risk of errors.

Conclusions: The similarity in the names of two active ingredients can lead to medication errors that endanger patients' lives. The reporting of these three cases highlights the need to pay special attention to the process of prescribing, dispensing and administering medicines by healthcare professionals, as well as the importance of pharmacovigilance in minimizing medication-related risks.

#50

Assessment of avoidable hospital admissions due to adverse drug reactions at Virgen Del Rocío University Hospital

J. Navarro Roldan¹, C. M. Jiménez Martín¹, A. Melcón De Dios², E. M. Perez Lopez¹, L. M. Rojas Herrera¹ and M. P. Maiquez Asuero¹

¹UGC Farmacología Clínica, Hospital Universitario Virgen del Rocio, Sevilla, Spain; ²UGC Farmacología Clínica, Hospital Universitario Virgen Macarena, Sevilla, Spain

Objective: To analyse potentially preventable adverse drug reactions (ADRs) that led to hospital admissions at Virgen del Rocío University Hospital in the first half of 2020.

Material and/or methods: A descriptive analysis was conducted using data from the minimum basic dataset at hospital discharge (CMBDH) coded within the ICE-10 range: T36.0X1A-T50.996S. Two hundred fifty-one records were identified, with 97 evaluated after applying exclusion criteria. The Spanish Pharmacovigilance System algorithm and the Schumock and Thornton questionnaire were used to determine the causality and preventability of the ADRs.

Results: 58.76% of patients were women, with a median age of 60 years. All cases were severe, with 39.56% life-threatening and 4.12% fatal. Upon discharge, 83.50% had recovered, 8.24% were recovering, and 4.12% had sequelae. The 97 patients presented 187 ADRs, most frequently affecting the nervous (N = 49) and gastrointestinal systems (N = 29). The most common were acute respiratory failure and decreased consciousness. Most (96.9%) had a known drug-ADR relationship, with probable causality in 65.97% of cases. Drugs most frequently implicated belonged to the nervous system group. In 29.9% of cases, ADRs were due to interactions.

At least one preventability criteria was met in 24.74% (N = 24), with a known ADR-drug relationship in all cases. Positive re-exposure occurred in two cases. No significant association was found between age, sex and preventable nature of the ADRs. 45.8% of them caused a potential life-threatening situation, with one fatality. Upon discharge, 87.5% had recovered. The 24 patients presented 48 ADRs, most frequently affecting the nervous system (N = 14). The medications most often implicated belonged to the nervous system group.

Conclusions: Most identified ADRs were known and predominantly affected the central nervous system. 24.74% of ADRs were preventable, highlighting the importance of correct prescription and treatment monitoring. This study is part of a broader review evaluating ADR reports over the last 5 years.

#64

Improving side effects assessment in people with Down syndrome using pictograms

P. Diaz Pellicer¹, A. M. Aldea Perona², M. Pérez Otero², L. Forcano Gamazo¹ and R. De La Torre Fornell¹

¹Human Pharmacology and Clinical Neurosciences Research Group, Hospital del Mar Research Institute, Barcelona, Spain; ²MARTrial. Hospital del Mar Research Institute, Barcelona, Spain

Objective: To develop an instrument based on pictograms able to assess adverse drug reactions (ADRs) in individuals with Down syndrome (DS).

Material and/or methods: Thirteen experts from different disciplines (physicians, nurses, drug safety, mental health and medical ethics) selected 15 ADRs that could benefit most from a pictographic representation using the Delphi methodology. Pictogram comprehension was evaluated in young adults with DS (N = 15) using transparency and translucency tests. To evaluate transparency, participants were asked to interpret each pictogram without prior knowledge of their meanings. Responses were scored as correct, partially correct, incorrect or no response by three independent reviewers. To assess translucency, participants rated how well the pictogram represents its meaning on a visual analogue scale of 1–7. The local institutional review board approved the study. Participants signed an informed consent.

Results: The selected ADRs were restlessness, palpitations, headache, pins and needles, dizziness, vomiting, fatigue, nausea, muscular pain, ringing in ears, feeling sad, itchy, insomnia, flatulencies and somnolence. In the transparency test, five pictograms were interpreted correctly or partially correctly for ≥80% of the participants (vomit, muscular pain, ringing in ears, feeling sad and somnolence). In the translucency test, 10 pictograms achieved 5 points or more from ≥80% of the participants (palpitations, headache, dizziness, vomiting, muscular pain, ringing in ears, feeling sad, itchy, flatulencies and somnolence). Results show that pictograms are better understood when accompanied by oral explanations.

Conclusions: Results show that pictograms are generally well understood by individuals with DS. The study suggests that using certain pictograms, along with oral explanations, can be a valid method to assess the presence of ADRs in individuals with DS. The next step is to validate the instrument in the framework of clinical research.

#68

Impact of a multifaceted intervention programme on antibiotic prescribing and dispensing in four patient-centred settings in five European countries

A. Garcia Sangenis^1,2, R. Monfa Escola¹, R. Morros Pedros^1,2, A. Moragas Moreno^1,3 and C. Llor Vila^1,4

¹IDIAPJGol, Barcelona, Spain; ²CIBERINFEC, Madrid, Spain; ³Institut Catala de la Salut, Tarragona, Spain; ⁴Institut Catala de la Salut, Barcelona, Spain

Objetive: The primary cause of antimicrobial resistance is excessive and non-indicated antibiotic use. The objective of this project was to evaluate the impact of a multifaceted intervention aimed at various healthcare professionals (HCP) on antibiotic prescribing and dispensing for common infections.

Material and/or methods: Following the Audit Project Odense method, HCPs from general practice, out-of-hours services, nursing homes and pharmacies across five European countries (France, Greece, Lithuania, Poland and Spain), self-registered encounters with patients related to antibiotic prescribing and dispensing before and after an intervention (February–April 2022 and February–April 2023). Prior to the second registration, the HCPs undertook a multifaceted intervention, which included reviewing and discussing feedback on the first registration's results, enhancing communication skills by means of a 2-h workshop and providing communication tools. A quality indicator on potentially unnecessary antibiotic prescription was developed for each diagnosis in the different settings by the consortium. The results of the two registrations were compared.

Results: A total of 345 HCPs registered 10 744 infections in the first registration period and 10 207 infections in the second period. In general practice, participants showed a significant 9.8% reduction in unnecessary antibiotic prescriptions in the second period, whereas limited or no effect was observed in out-of-hours services and nursing homes, with a 0.8% reduction and 4.5% increase, respectively. Community pharmacies showed an 18% increase in safety checks, and correct advice in pharmacies rose by 17% after the intervention.

Conclusions: Antimicrobial stewardship programmes are slightly effective in improving antimicrobial utilization. However, the effectiveness is not the same across different settings and countries, and some external factors, mainly the COVID pandemic in the first registration and shortage of narrow-spectrum antibiotics and a streptococcal epidemic during the second registration, might have hampered the benefits of this intervention.

#71

Review of CAR-T therapies' reports to the pharmacovigilance centre of Cantabria

I. Mazón Maraña¹, D. Z. Cuellar Gómez², M. González Ruiz¹, M. Sánchez Escamilla³, J. M. Cerezo Martín³, Á. Cadenas Manceñido² and M. García Saiz²

¹Pharmacovigilance Center of Cantabria, Clinical Pharmacology Service of the Primary Care Management, Santander, Spain; ²Clinical Pharmacology Service, Marqués de Valdecilla University Hospital, Santander, Spain; ³Hematology Service, Marqués de Valdecilla University Hospital, Santander, Spain

Objective: To evaluate the safety profile of CAR-T therapies, to determine the incidence of adverse drug reactions (ADRs) and to identify possible alerting cases.

Material and/or methods: A review of the clinical history and spontaneous reports (SR) from healthcare professionals of patients from Cantabria who presented ADRs in relation to CAR-T therapies administered between June 2018 (beginning of use of CAR-T in centres outside our community) and September 2023.

Results: Of 31 patients treated until 05/01/2024, 17 SR have been received (incidence of 54%): 10 of them with Yescarta (axicabtagene ciloleucel [58.8%]), six with Kymriah (tisagenlecleucel [35.3%]) and one with Tecartus (brexucabtagén autoleucel [5.9%]). The indication in 100% of the patients was non-Hodgkin's B-cell lymphoma. The median age was 62 years [range 37–76], with nine [53%] women and eight [47%] men. The main ADRs in the 31 patients were cytokine release syndrome (15 [48.4%]), immune effector cell-associated neurotoxicity syndrome (11 [35.5%], described with the following symptoms: alteration of gait, bradypsychia, dysgraphia, cerebral oedema, micrography, paresthesias, drowsiness and tremor), cytopenias (8 [25.8%]) and different infections (5 [16.1%]). All cases have been considered serious due to clinical significance with two fatal ADRs [6.4%]: cerebral oedema and necrotizing pneumonia. Four ADRs were considered alerting cases: Squamous cell carcinoma of the lung, interstitial pneumonitis, sarcoidosis and bradycardia and are currently being followed up for consideration as a possible signal. The n does not allow establishing significant differences between the CAR-T.

Conclusions: The results are consistent with what is described in the Summaries of Product Characteristics (SPC); however, the appearance of unexpected and potentially fatal ADRs reaffirms the importance of collaborating with hospital services to establish an early report circuit that monitors the post-marketing safety of novel therapies such as the CAR-T.

#74

Incidence of ferric carboxymaltose hypophosphatemia in iron deficiency anaemia in patients undergoing surgery for digestive neoplasia

H. Guardiola Ponti^1,2, I. Hernández Rodríguez³, J. Grau Cat³, S. Martínez Couselo⁴, A. Sancho Cerro⁴, C. Joaquin Ortiz^5,6, A. E. Ramos Rodas⁵, E. Garsot Savall⁷, Y. Jiménez Capel⁸ and E. Montane Esteva^2,9

¹Polyvalent Day Care Hospital, Hospital Germans Trias i Pujol, Badalona, Spain; ²Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Bellaterra, Spain; ³Hemathology Department, Catalan Institut of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain; ⁴Clinical Analysis and Clinical Biochemistry Department, Laboratory Clinic Metropolitana Nord, Hospital Germans Trias i Pujol, Badalona, Spain; ⁵Endocrinology and Nutrition Departament, Hospital Germans Trias i Pujol, Badalona, Spain; ⁶Faculty of Medicine, University of Vic, Vic, Spain; ⁷Head of Upper GI, Surgery General and Digestive Surgery, Hospital Germans Trias i Pujol, Badalona, Spain; ⁸Anesthesiology, Resuscitation and Pain Management, Hospital Germans Trias i Pujol, Badalona, Spain; ⁹Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

Objective: To determine the prevalence of preoperative hypophosphatemia in patients undergoing surgery for digestive neoplasia, treated in the previous 2–3 weeks with ferric carboxymaltose (FCM) to remedy preoperative anaemia.

Material and/or methods: Prospective, single-centre observational study of a cohort of patients with iron-deficiency anaemia secondary to gastrointestinal tract neoplasia, who received treatment with FCM before surgery. Prophylactic phosphate supplements were given when the pre-surgical control showed phosphate levels below 3 mg/dl. Demographic, clinical and analytical variables of preoperative iron and phosphocalcium metabolism, as well as up 3 months postoperative complications, were collected.

Results: Fifty-one patients with digestive neoplasia were included, of which 58.8% (30/51) were men with a median age of 75 years (range 45–92). Six patients (11.8%) had a glomerular filtration (GF) < 60 ml/min. The median iron deficiency calculated with the Ganzoni formula was 712 mg (range 500–1600 mg), and the median of received FCM dose was 1000 mg (range 500–2000). The prevalence of hypophosphatemia was 51% (26/51) being severe (phosphate <1.5 mg/dl) in 5.9% of the cases (3/51). Eighteen patients (60%) with hypophosphatemia had previously received prophylactic phosphate supplements. Fifteen patients (29.4%) suffered complications within 90 days after surgery, and one patient (2%) was exitus. Hypophosphatemia was more frequent in patients who received doses of FCM > 1000 mg (72.2% vs. 39.4%; p = 0.025) and to be women was a trend (66.7% vs. 40%; p = 0.06). It was not associated with other risk factors such as renal failure or baseline phosphatemia <3.1 mg/dl or the occurrence of postoperative complications.

Conclusions: The prevalence of FCM-induced hypophosphatemia in patients undergoing surgery for digestive neoplasia was higher than expected, specially considering that more than half of them were previously treated with prophylactic phosphate supplements. FCM-induced hypophosphatemia was associated with high doses of FCM.

#88

Risk of cancer in patients with inflammatory bowel disease and prior or current cancer treated with biologic therapies: A systematic review

C. Sans Pola^1,2,3, M. Bosch^1,2,3, L. Camacho^1,2,3 and I. Danés Carreras^1,2

¹Hospital Universitari Vall d'Hebron, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Bellaterra, Spain; ³Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain

Objective: Managing inflammatory bowel disease (IBD) in patients with current or previous cancer is challenging. This systematic review aims to discuss the current evidence of the risk of cancer associated with biologic therapies in patients with IBD who have prior/current cancer.

Material and/or methods: We performed this systematic review according to the guidelines of the PRISMA 2020 statement. We identified studies through comprehensive searches of Embase and MEDLINE up to May 2024. Eligible studies were those patients with IBD, and prior or current cancer treated with biologics compared to patients treated with other immunomodulators (IMM) or no IMM. We assessed the risk of bias with the National Institutes of Health (NIH) Quality Assessment Tool for non-randomized studies. The protocol is registered on PROSPERO (CRD42022345746).

Results: Of 4383 records identified, 13 were eligible for inclusion after screening. Eleven (85%) were retrospective cohort studies, while the remaining were prospective. Most studies were rated as fair or good quality. All studies included patients treated with anti-TNFs, and seven included vedolizumab +/− ustekinumab. In 10 studies, patients exposed to biologics were compared to patients not exposed to IMM. The follow-up time ranged from 21 to 68.5 months. In 10 studies, different types of cancer were included and in three, only one type: breast cancer (1) and non-melanoma skin cancer (NMSC) (2). Most studies did not find an increased risk of cancer recurrence with biologics compared to no IMM. Two studies suggested an increased risk of NMSC recurrence with anti-TNFs; however, due to methodological issues, this cannot be confirmed in patients with IBD.

Conclusions: The number of studies that include patients with IBD and prior/current cancer is scarce. Most studies were retrospective and methodologically diverse, and reported no significant increase in risk with biologics compared to no IMM. Larger prospective studies are needed to further assess their long-term safety profile.

#91

Safety and effectiveness of nasal esketamine in treatment-resistant depression

D. Z. Cuéllar Gómez¹, I. Mazon Maraña², M. Gonzalez Ruiz², F. Perez Hernández³ and M. I. Priede Diaz⁴

¹Clinical Pharmacology Service, Marqués de Valdecilla University Hospital, Santander, Spain; ²Pharmacovigilance Center of Cantabria, Clinical Pharmacology Service of the Primary Care Management, Santander, Spain; ³Pharmaceutical Management Service, General Directorate of Pharmacy, Humanization and Socio-Health Coordination, Ministry of Health, Government of Cantabria, Santander, Spain; ⁴General Directorate of Pharmacy, Humanization and Socio-Health Coordination, Health Counseling, Government of Cantabria, Santander, Spain

Objective: Esketamine nasal spray (ESK-NS) is used in major depression resistant to treatment (TRD). Due to its safety profile, it is only available under a special prescription and must be taken under direct supervision of a healthcare professional. We assessed the effectiveness and safety of esketamine in the first 50 patients with TRD treated in Cantabria.

Material and/or methods: Clinical characteristics, safety and efficacy data were reported by physicians in patient's medical history. Effectiveness was assessed with the Montgomery–Asberg Depression Rating Scale (MADRS). Safety was reviewed, and all adverse drug reactions (ADR) to ESK-NS were reported to the Spanish Pharmacovigilance System. Patients were followed up to June 2024.

Results: The cohort (n = 50; 64% female and 36% male; median age 54; 100% with moderate/severe mayor TRD) received ESK-NS induction treatment for 4 weeks, from August 2020 to June 2023. Among 32 patients with basal MADRS records, 17 (53.1%) achieved response (MADRS reduction ≥50%), and 15 (46.9%) achieved remission (MADRS ≤12). Four patients (12.5%) had no post-induction MADRS record. All patients presented at least one ADR: CNS (88%), psychiatric (78%), digestive (28%), ORL (22%), renal (12%), general (10%) and cardiovascular (8%). Dizziness, sleepiness and dissociation were reported in more than 50% patients.

Induction was followed by maintenance phase in 28 (56%) patients, with a median duration of 149 (17–298) days. Maintenance-related MADRS was recorded only in six (21.4%) patients, and similar ADR as in induction phase were reported in 22 (78,6%) patients.

Conclusions: The safety and efficacy of esketamine in our cohort is consistent with that established in clinical trials. No new safety signals were identified. MADRS should be always recorded during the maintenance phase to properly assess stable remission/response rates.

#92

Comparative immunogenicity of original/BA.4/BA.5-adapted bivalent BNT162b2 MRNA vaccine and the bivalent PHH-1V recombinant protein as a fourth dose

I. Darnaude Ximénez¹, F. Díez Fuentes^2,3, M. Deulofeu⁴, M. Bermejo^2,3, L. Vicente¹, M. Aparicio⁵, L. Ferrer⁴, C. Avendaño Solá¹, M. Pérez Olmeda⁶ and J. García Pérez^2,3

¹Clinical Pharmacology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain; ²AIDS Immunopathogenesis Unit. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain; ³Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain; ⁴HIPRA, Girona, Spain; ⁵Occupational Risk Prevention Service, Hospital Universitario Puerta de Hierro-Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain; ⁶Laboratorio de Serología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain

Objective: Booster immunization against SARS-CoV-2 remains the main strategy for dealing with SARS-CoV-2 in vulnerable populations. Immunization can be achieved by mRNA, protein adapted vaccines or their combination. Our study aims to compare the immune response generated by an adapted bivalent booster mRNA vaccine (Original/BA.4-5) and a recombinant protein RBD fusion heterodimeric vaccine (Alpha/Beta) against the main circulating variants.

Material and/or methods: Longitudinal cohort prospective study of 60 healthy volunteers recruited at the Puerta de Hierro Hospital who received the fourth dose of the bivalent mRNA vaccine (adapted BNT162b2) and 15 healthy volunteers that received a fourth dose with the heterodimeric vaccine (PHH-1V) (EudraCT: 2021-005226-26). All participants had received three previous doses of BNT162b2. Sera were collected at pre-vaccination (V1), 14 days_PHH-1V or 28 days_BNT162b2 (V2), 90 days (V3) and 180 days (V4). Antibody-mediated immune responses were assessed by two commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay.

Results: Mean age of participants was 34.4 years (BNT162b2) and 47.7 years (PHH-1V) with 28% (BNT162b2) and 53% (PHH-1V) male participants. SARS-CoV-2 anti-nucleocapsid antibodies, suggesting recent infection, were detected in 39 participants (65.0%) at basal visit in BNT162b2 arm, with at least six breakthrough infections during the study period (28.6%). In PHH-1V arm, no subjects had anti-nucleocapsid antibodies prior to vaccination, and six (40.0%) became positive during the study.

All participants showed saturated values of total anti-RBD Igs at V2. Higher neutralizing antibody titres were found against Alpha and Beta variants in subjects vaccinated with PHH-1V at V2 and V3 (p < 0.01). No differences between vaccines were found at any other time point or against Omicron variants (BA.1, BA4/5, XBB.1.5 and XBB.1.16).

Conclusions: BNT162b2 and PHH-1V generated a comparable neutralizing response against several SARS-CoV-2 variants, including the more evolved Omicron lineages XBB.1.5 and XBB.1.16.

#93

Response to treatment in anti-HMGCR antibody-associated necrotizing autoimmune myopathy: A case series study from a referral hospital in Asturias, Spain

E. Salgueiro Vázquez¹, J. Fra Yáñez^1,2, G. Morís De La Tassa^1,3 and L. Mozo Avellaned⁴

¹Universidad de Oviedo, Oviedo, Spain; ²Unidad de Farmacia, Dirección Atención y Evaluación Sanitaria del SESPA, Oviedo, Spain; ³Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain; ⁴Servicio de Inmunología, Hospital Universitario Central de Asturias, Oviedo, Spain

Objective: There is no standard treatment strategy for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody-associated myopathy. The aim of our study was to assess the outcome of treatment strategies of patients with anti-HMGCR antibody-associated myopathy to improve their medical management.

Material and/or methods: This is a retrospective study based on electronic medical records. A series of cases of anti-HMGCR autoimmune myopathy were collected at the Hospital Universitario Central de Asturias (HUCA) between 2015 and 2023. Data on demographics, statin exposure, clinical and laboratory findings, treatment strategies and outcomes were collected.

Results: A total of 10 patients (5:5 females/males) with anti-HMGCR autoimmune myopathy were collected. The median (range) age was 65 (52–76) years. All the patients had been exposed to statin for a mean ± SEM of 4.1 ± 0.5 years. Mean ± SEM maximum creatine kinase (CK) level (n = 9): 5641.1 ± 1642.5 U/L. All patients had positive anti-HMGCR antibodies. 9/10 patients presented significant muscular symptoms. Statin was withdrawn in all cases. One patient improved without drug therapy. Mean ± SEM of treatment strategies received by patients (n = 7): 5 ± 0.5. As induction therapy, 3/10 patients were treated with intravenous (IV) glucocorticoids (GC) (6-methylprednisolone 250 mg, three bolus), three other patients were treated with a double induction [azathioprine or methotrexate or IV immunoglobulin (Ig) + GC], and one received IV-Ig (25 g/d 5 days, 3 cycles/month). The maintenance therapy was based on steroid-sparing immunosuppressant (azathioprine or methotrexate or tacrolimus or rituximab, with or without IV-Ig) + a progressive tapering of GC. Remission was achieved in these seven patients while maintaining treatment, and at the last follow-up, they were still on treatment. Relapse rate was 4/10.

Conclusions: After statin withdrawal, one patient had satisfactory improvement without pharmacological treatment (two others without treatment record). All other patients needed between three and seven consecutive treatment schemes based on GC and immunosuppressants or rituximab with or without IV-Ig to achieve remission.

#96

Toxicity secondary to high doses of ceftazidime, a case report

R. Ordorica López, R. C. Alvarez Cabrera, Á. Cadenas Manceñido, M. B. Sánchez Santiago, N. Vega Gil and M. M. García Saiz

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Objective: To present a case of toxicity secondary to high-dose ceftazidime, to assess clinical finding due to administered doses and to discuss patient's clinical course.

Material and/or methods: Descriptive observational case report study.

The clinical information was extracted from the patient's medical record called ‘Altamira’. Information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for Medicines and Medical Devices (AEMPS). A non-systematic bibliography research has been made.

Results: We report the case of a patient admitted to our hospital due to a left hip infection with a positive culture for Pseudomonas aeruginosa. As the infectious agent was resistant to carbapenems and quinolones, treatment was started with ceftazidime at a dose of 2 g/8 h. Subsequent to the introduction of this antibiotic, he developed a clinical manifestation characterized by myoclonus in the trunk and upper limbs, accompanied by slight dysarthria. In view of the temporal relationship, the high dose of ceftazidime and the characteristics of the symptoms, he was diagnosed with status epilepticus secondary to beta-lactam intoxication. Therefore, ceftazidime was discontinued.

Finally, after treatment with rivotril and levetiracetam, the clinical condition associated with ceftazidime treatment cleared up.

Conclusions: The adverse reactions described in the different drugs, whether frequent or not, should be widely known by the professionals who make use of them in order to be able to recognize them and act quickly before a possible fatal outcome.

Sometimes, the least frequent adverse reactions are the most lethal.

#97

Cholinergic syndrome associated to dexchlorpheniramine, a case report

R. Ordorica López, Á. Cadenas Manceñido, R. C. Álvarez Cabrera, M. B. Sanchez Santiago, N. Vega Gil and M. M. García Saiz

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Objective: To present a cholinergic syndrome due to the use of dexclorfeniramine, to discuss the differential diagnosis proposed for the clinical findings and to outline therapeutic measures used to manage the syndrome.

Material and/or methods: Descriptive observational case report study.

The clinical information was extracted from the patient's medical record called ‘Altamira’. Information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for Medicines and Medical Devices (AEMPS). A non-systematic bibliography research has been made.

Results: We report the case of a patient seen in the emergency department of our hospital who suddenly showed signs of generalized wheal exanthema and received intravenous treatment consisting of 60 mg of methylprednisolone and 5 mg of dexchlorpheniramine.

After the administration of these drugs, she suddenly experienced dystonia, akathisia/clonias in the upper and lower extremities, anxiety, chest pain, dyspnoea and dry mucous membranes. In view of the symptoms, it was decided to keep the patient under observation with electrocardiographic monitoring, which revealed spells of non-sustained ventricular tachycardia. In view of the temporal association, an acute anticholinergic syndrome was suspected as a result of the administration of dexchlorpheniramine. Finally, after administration of rivotril, the patient's condition improved, and after close monitoring for 24 h, discharge home was decided.

Conclusions: The adverse reactions described in the different drugs, whether or not they are frequent, should be well known by the professionals who use them in order to be able to recognize them and act quickly before a possible fatal outcome.

#104

Eosinophilic gastrointestinal disorders associated with alemtuzumab, report of a case

M. González Ruiz¹, I. Mazón Maraña¹, D. Z. Cuellar Gómez², L. Lavín Alconero³, A. Llorente Cantalapiedra² and J. Pardo Lledias⁴

¹Pharmacovigilance Center of Cantabria, Clinical Pharmacology Service of the Primary Care Management, Santander, Spain; ²Clinical Pharmacology Service, Marqués de Valdecilla University Hospital, Santander, Spain; ³Clinical Trials Agency Valdecilla-IDIVAL, Marqués de Valdecilla University Hospital, Santander, Spain; ⁴Internal Medicine Service, Marqués de Valdecilla University Hospital, Santander, Spain

Objective: Alemtuzumab is an anti-CD52 monoclonal antibody used to treat active relapsing–remitting multiple sclerosis. Eosinophilic gastrointestinal disorders (EGIDs) are defined as rare disorders with non-specific inflammatory symptoms and high eosinophilic infiltrate in tissue biopsy. Despite an extensive literature review, no previous cases of alemtuzumab-induced EGIDs have been published.

Material and/or methods: We describe the first case of eosinophilic gastroenteritis (EGE) secondary to alemtuzumab reported in Spain. We also review all the drug-related EGIDs reported to the Spanish Pharmacovigilance System (SEFV), as well as similar cases contained in EudraVigilance. EGIDs terms reviewed included esophagitis, gastritis, gastroenteritis, enteritis and colitis.

Results: A 61-year-old female patient received treatment with alemtuzumab in 2018–2019 for multiple sclerosis. In 2020, she began to experience abdominal pain with non-specific symptoms and weight loss. Upon admission in November 2020, she presented nauseas, vomiting, abdominal wall oedema and elevated eosinophilia. A gastric biopsy confirmed the diagnosis of EG with associated protein loss syndrome likely to be induced by drugs. Cancer, vasculitis, parasites and other alternative causes were excluded. Treatment with corticosteroids was starded and histological findings improved, but active disease persists as of 2024.

The SEFV database contained a total of 26 EGIRs reports, but only our case related to alemtuzumab. A search carried out in EudraVigilance found another two cases of EGIDs related to alemtuzumab that increase the value of this drug adverse reaction association.

Conclusions: As alternative causes were excluded, alemtuzumab was considered as the main trigger due to its temporal correlation, mechanism of action and potential risk of immune disorders. However, more research is needed to understand the mechanism of EGID secondary to drugs. EG secondary to alemtuzumab is currently being followed up for consideration as a possible signal. It is important to maintain an active pharmacovigilance network to make early detections of rare adverse reactions.

#106

Hepatitis associated with turmeric consumption

R. Pardo Puras, M. Álvarez Montero and E. Ramírez García

Hospital Universitario La Paz, Madrid, Spain

Objective: Turmeric and its purified extract curcumin are popular herbal dietary supplements used for their purported anti-inflammatory and antioxidant effects that have been implicated in causing liver injury. Until now, they were considered safe and even shown to have hepatoprotective properties.

Material and/or methods: All adjudicated cases enrolled in drug liver injury (DILI) since 2023 in the pharmacovigilance department in which turmeric was an implicated product were studied. Causality was assessed using the Spanish pharmacovigilance algorithm, and the suspected underlying immune mechanism was studied through the lymphocyte transformation test.

Results: In this case report, three cases of DILI that were assessed through pharmacovigilance consultation are presented. All patients were women aged 46–69. Two patients underwent liver biopsy revealing mild hepatocellular DILI. Lymphocyte transformation tests were positive in both patients tested. None required hospitalization and all recovered upon discontinuing curcumin intake. RUCAM final scores were +11, +8 and +7.

Conclusions: In the Hospital Universitario La Paz, we have identified three cases related to the consumption of this supplement these past 2 years, which correlate with the findings stated before. Turmeric causes potentially severe liver injury that is typically hepatocellular, emphasizing the importance of recognizing the potential adverse effects of herbal dietary supplement given the rise of their popularity.

#113

Sarcoidosis-like disease (SLD) associated with CAR-T therapy, a case report

I. Mazón Maraña¹, D. Z. Cuellar Gómez², M. González Ruiz¹, M. Sánchez Escamilla³, J. M. Cerezo Martín³ and M. García Saiz²

¹Pharmacovigilance Center of Cantabria, Clinical Pharmacology Service of the Primary Care Management, Santander, Spain; ²Clinical Pharmacology Service, Marqués de Valdecilla University Hospital, Santander, Spain; ³Hematology Service, Marqués de Valdecilla University Hospital, Santander, Spain

Objective: Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy that has resulted in tremendous progress in the treatment of B-cell malignancies. However, the efficacy of the therapy is not free of safety concerns, including the absence of information on subsequent autoimmune phenomena.

Material and/or methods: To describe the case of a patient diagnosed with sarcoidosis after administration of CAR-T: Kymriah (tisagenlecleucel) and the cases found in the literature and in European territory through EudraVigilance.

Results: Sixty-nine-year-old male patient with diffuse large B-cell lymphoma. No personal history of autoimmune diseases but soon diagnosed with pulmonary sarcoidosis. Treated with CAR-T in March 2021 with good response. In July 2022, he was evaluated for the appearance of pleural hypermetabolic lesions on PET. A puncture was performed to characterize hilar/mediastinal lymphadenopathy, finding the presence of granulomas without necrosis. The diagnosis of sarcoid reaction is confirmed with bone marrow biopsy: epithelioid granulomatosis (previous biopsy in 2020 non-pathological). In asymptomatic patient, no treatment is considered necessary and continues with annual follow-up. After evaluating the reported case, a search was carried out in EudraVigilance, finding two cases, one with Kymriah and the other with Yescarta (brexucabtagene autoleucel). A PubMed search found an article from January 2023 presenting another case in multiple myeloma with Ide Cel (idecabtagene vicleucel). These findings increase the value of the drug adverse reaction association described.

Conclusions: Treatment with CAR-T therapy was associated as the main trigger due to its temporal correlation, its mechanism of action and the absence of alternative causes. Patients with autoimmune diseases were generally excluded from clinical trials, and the impact of these treatments on both pre-existing conditions and predisposing patients is unknown. SLD secondary to CAR-T therapy is currently being followed up for consideration as a possible signal. It is important to maintain an active pharmacovigilance network to make early detections of novel therapies such as CAR-T.

#20

Use of glucarpidase on high-toxic methotrexate levels, a case report

Á. Cadenas Manceñido, R. Ordorica López, R. C. Álvarez Cabrera, M. A. Cos Cossío, M. B. Sánchez Santiago, L. Lavín Alconero, N. Sánchez Avello and M. M. García Saiz

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Objective: To describe a case of pharmacokinetic interaction between levetiracetam and methotrexate, which resulted in antimetabolite toxic level, causing a secondary severe renal injury; to expose one single case experience on the use of glucarpidase for the treatment of methotrexate delay elimination; and to correlate serum methotrexate levels measured by two different lab techniques, such as high-performance liquid chromatography (HPLC) and radioimmunoassay technique (RIA).

Material and/or methods: Descriptive observational case report study. The clinical information was extracted from the patient's medical record. Therapy drug monitoring (TDM) information was obtained from departamental application ‘Modulab’.

A non-systematic review of the literature was set in order to assess the use of glucarpidase in similar cases.

Part of the information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for Medicines and Medical Devices (AEMPS).

Results: A clinically significant interaction between levetiracetam and methotrexate has been set, congruent with the previous literature. No mechanism known has been proposed as responsible; interaction between these two drugs is unclear.

Evolutive plasmatic methotrexate levels were measured by RIA technique, available on our centre, and also by HPLC, which was available on external one, and have been compared with literature, specially with those exposed on glucarpidase use consensus guidelines.

Antimetabolite levels after just one single dose of methotrexate were measured and remained positive 400 h after the intravenous administration.

Conclusions: Plasmatic level pattern behaved as expected after glucarpidase administration, as well as determined by RIA or by HPLC.

Administration of glucarpidase administration was effective in helping to decrease plasma methotrexate levels.

#22

Therapeutic drug monitoring with artificial intelligence: Current status

D. Fondevila Batista, C. Boada Fernandez Del Campo, C. Rodriguez Jimenez, C. N. Grillo, J. L. Rollingson Landaeta, C. Velazquez Perello, M. García Sanchez-Colomer, E. Fernandez Quintana, J. A. Fernandez Rodriguez and E. J. Sanz Alvarez

Hospital Universitario de Canarias, San Cristobal De La Laguna, Spain

Objective: To determine the current ability (including reproducibility of results) of various artificial intelligences (AIs) and to indicate therapeutic dose adjustments in TDM for specific patients, compared to the adjustment by a clinical pharmacology specialist (gold standard).

Material and/or methods: For the analysis, we chose five clinical cases previously assessed in the Clinical Pharmacology Department of the Hospital Universitario de Canarias (CHUC). We used free versions of AIs (ChatGPT 3.5®, Gemini®, TextCortex®) not trained for the proposed purpose.

The anonymized individual cases were initially loaded into the AIs in Spanish, ‘copying and pasting’ a ‘standard wording’ for each case, to avoid differences in the wording that could influence the analysis of the cases between each AI. The process was then repeated for the English language.

Finally, we compared the doses proposed by the AIs between themselves and with each other, in both languages with those recommended by the clinical pharmacology specialist. Also, we reintroduced the same case, even in the same language, in each AI to see the reproducibility of the results.

Results: There is great variability in the results offered, both inter/intra AI for each case, between languages, and even reintroducing the same case. Rarely do the proposed doses coincide with the gold standard.

Conclusions: (1) Untrained AI is currently not a valid and reliable method to perform TDM. (2) The variability in the doses proposed by the same AI, after reintroducing a specific case, invalidates the method of analysis of the AI in question (non-reproducibility). (3) We cannot rule out that a trained AI can provide more accurate and reproducible results.

#34

Application of a pharmacokinetic monitoring tool in clinical practice: A personalized approach to antimicrobial monitoring

J. M. Dodero Anillo, M. Fernández-Pujol Marzo, M. E. Pacheco Rodríguez, J. B. Raffo Nogueira, L. Bello Bello and M. J. Pedrosa Martínez

Hospital Universitario Puerto Real, Puerto Real, Spain

Objective: To evaluate the application of DoseMe®, a therapeutic drug monitoring tool, in the Clinical Pharmacology Service of a second-level hospital, Puerto Real University Hospital.

Material and/or methods: In this project, the monitoring tool ‘DoseMe®’ was used to adjust doses of systemic antimicrobials, specifically vancomycin and aminoglycosides. A patient database was created at Puerto Real University Hospital, covering the period from 1 April 2023 to 30 April 2024. Prescriptions were closely followed up before adjustments, with trough levels requested. Dose adjustments were made using DoseMe®, and the prevalence of patients reaching therapeutic ranges post-adjustment was calculated.

Results: There were 195 vancomycin prescriptions, of which 93 required dose adjustment due to supra- or subtherapeutic trough levels. After dose adjustments with DoseMe®, 92.31% reached the therapeutic range, while 7.69% did not despite the adjustment. Additionally, 18 patients were treated with amikacin, of whom eight required adjustments. Of these, 50% reached the therapeutic range after the adjustment. Furthermore, 58 patients were treated with gentamicin, with 12 levels reported, four of which required adjustment, and 75% achieved the therapeutic range after adjustment. In the case of tobramycin, four patients were recorded, but no trough levels were received from the responsible services, so dose adjustments could not be made.

Conclusions: The application of the DoseMe® monitoring tool allowed us to properly adjust doses in a large proportion of patients treated with antimicrobials, improving our data collected in previous years without the intervention tool (80% in 2022). We emphasize the value of customizing treatment by considering the pharmacokinetic parameters of patients using monitoring tools designed for this purpose. However, we believe it is necessary to collect more data through prospective studies in order to evaluate the final efficacy of the tool used.

#35

Establishing new paradigms: Therapeutic drug monitoring (TDM) of oral vancomycin

J. B. Raffo Nogueira, L. Bello Bello, M. Fernández-Pujol Marzo, M. E. Pacheco Rodríguez, M. J. Pedrosa Martínez and J. M. Dodero Anillo

Hospital Universitario Puerto Real, Puerto Real, Spain

Objective: To establish universal criteria for systematic monitoring of vancomycin levels when administered orally, aiming to prevent potential complications, particularly in elderly and critically ill patients.

Material and/or methods: In mid-2021, the Clinical Pharmacology Unit at Puerto Real University Hospital was tasked with investigating the potential oral absorption of vancomycin and determining whether monitoring of serum concentration is necessary. After reviewing the literature available at the time, we encountered published a few cases illustrating not only clinical significance levels but also toxic levels that had led to impaired renal function. Furthermore, in certain healthcare systems, recommendations were made for systematic monitoring when specific criteria were met. In 2022, we began advocating for monitoring across various units that could potentially administer oral doses based on the presence of at least two of the following criteria: renal compromise, ICU patients, polypharmacy with other potential nephrotoxins, intercurrent severe inflammatory bowel disease and age 65 or above. Sample analysis was conducted using the ARCHITECT i1000SR immunoassay analyser, as is customary in our clinical practice.

Results: From December 2022 to April 2024, we dissected a total of 74 cases, of which 46 met one or more of the specified criteria. We only managed to analyse 15 of them due to the lack of engagement across the different units, resulting in a 20% occurrence of cases with significance levels ranging from 5.6 to 9.61, with no toxicity involved.

Conclusions: There are recommendations emphasizing the importance of conducting individualized monitoring of vancomycin levels when administered orally, tailored to the patient's clinical context. Furthermore, we have identified clinical evidence supporting the absorption of oral vancomycin, reinforcing this notion. Therefore, we propose initiating a low-intervention trial to augment our sample size and enhance the validity of potential generalized monitoring criteria.

#49

Applying precision medicine to improve treatment of polymedicated patients with adverse drug reactions: A case report

E. M. Pérez López¹, J. L. Rubio Prieto², J. Navarro Roldán¹, M. E. Cordero Matía³, L. M. Rojas Herrera¹, P. Máiquez Asuero¹, H. C. Macher Manzano² and M. E. Segura Molina¹

¹Unidad de Gestión Clínica de Farmacología Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain; ²Unidad de Gestión Clínica Laboratorios (Bioquímica Clínica), Hospital Universitario Virgen del Rocío, Sevilla, Spain; ³Unidad de Gestión Clínica de Enfermedades Infecciosas, Microbiología y Parasitología, Hospital Universitario Virgen del Rocío, Sevilla, Spain

Objective: To highlight the role of pharmacogenetic testing in adjusting the treatment of a polymedicated patient who has presented multiple adverse drug reactions.

Material and/or methods: A 67-year-old woman with moderate hypotension, possibly due to an interaction between voriconazole and nifedipine. She also experiences somnolence that may be secondary to intrathecal morphine treatment or voriconazole toxicity. The Infectious Disease Department requests pharmacogenetic testing due to suspicion of treatment-related adverse reactions. Clinical and pharmacokinetic monitoring is performed to determine the causal relationship between the patient's symptoms and voriconazole blood concentrations.

Results: Relevant polymorphisms were identified in three genes: CYP2C19 gene (rapid voriconazole metabolism), COMT gene (reduced analgesic response to morphine, level of evidence 3) and OPRM1 gene (increased risk of adverse effects with morphine, level of evidence 3). Pharmacokinetic monitoring guided the dose adjustment of voriconazole until it was replaced by isavuconazole, whose metabolism does not depend on cytochrome CYP2C19. In addition, nifedipine was discontinued and the morphine dose was adjusted until symptoms improved.

Conclusions: Pharmacogenetic testing helps to guide treatment adjustments in polymedicated patients with suspected adverse reactions to multiple drugs. In some cases, the available scientific evidence is insufficient, and further pharmacological tests and clinical monitoring are required to optimize treatment. A multidisciplinary approach is essential to increase safety and provide the best possible care in the clinical setting.

#54

Pharmacogenetic insights into voriconazole metabolism in a patient with rectal cancer and invasive pulmonary aspergillosis

J. Navarro Roldán¹, J. L. Rubio Prieto², E. M. Pérez López¹, L. M. Rojas Herrera¹, P. Máiquez Asuero¹, H. C. Macher Manzano² and M. E. Segura Molina¹

¹UGC Farmacología Clinica, Hospital Universitario Virgen del Rocío, Sevilla, Spain; ²UGC Laboratorios (Bioquímica Clínica), Hospital Universitario Virgen del Rocío, Sevilla, Spain

Objective: To elucidate the pharmacogenetic profile influencing voriconazole metabolism in a patient with rectal cancer and invasive pulmonary aspergillosis, highlighting the clinical implications for personalized therapy.

Material and/or methods: A 50-year-old female with T3N0M0 rectal cancer developed Fournier's gangrene and invasive pulmonary aspergillosis following chemotherapy and radiotherapy. The patient was treated with meropenem and voriconazole 200 mg/12 h. Following treatment initiation, the patient experienced progressive isolated GGT elevation, with bilirubin and transaminases within range and supratherapeutic voriconazole levels, leading to treatment discontinuation. Persistent elevated levels post-withdrawal prompted pharmacogenetic testing of CYP2C19 and CYP3A4 genes using OpenArray® Pgx 120 express panel (Thermo Fisher^TM).

Results: Given the wild-type homozygous status for CYP2C19 and CYP3A4, additional testing included CYP2C9 and ABCB1 genes. The presence of the CYP2C9*3 allele in heterozygosis suggested intermediate metabolizer status. Voriconazole metabolism is primarily mediated by CYP2C19, with contributions from CYP2C9, CYP3A4 and FMO. Although CYP2C9 is involved in voriconazole N-oxidation, genotype–phenotype associations are unclear. The patient's intermediate metabolizer status for CYP2C9*3 and complex medical condition highlight the importance of pharmacogenetic profiling.

Conclusions: The identified CYP2C9 polymorphism challenges existing evidence on its role in voriconazole pharmacokinetics and underscores the utility of pharmacogenetic testing for optimizing antifungal therapy.

#57

Monitoring of plasmatic vancomycin level after intraperitoneal administration in dialysis-associated peritonitis

Á. Cadenas Manceñido, R. Ordorica López, R. C. Álvarez Cabrera, M. Martínez Belotto, M. D. L. O. Valentín Muñoz, M. B. Sánchez Santiago, L. Lavín Alconero and M. M. García Saiz

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Objective: To correlate vancomycin administered dose with its plasmatic value, to describe clinical variables of the sample, such as body mass index (BMI), and to expose microorganisms involved in intraperitoneal administered vancomycin peritonitis.

Material and/or methods: Descriptive observational study. Clinical information was extracted from the patient's medical records. Radioimmunoassay techniques were used to determine vancomycin plasmatic levels.

For all vancomycin levels, only from 1 January 2023 to 1 May 2024 were kept, representing 17 episodes from 11 patients.

Results: For all peritonitis episodes (17), only seven did not reach the optimal therapeutic plasmatic levels with a standard intraperitoneal vancomycin dose of 1000 mg each 96 h (29.4%). For nine episodes, the lower bound of the target levels were reached (52.9%), and for just one, the upper bound were achieved (5.9%).

For infratherapeutic levels, on four episodes, vancomycin dose was not changed, and just for one, clinical decision was to decrease the administered dose and reduce the administration interval to 500 mg/48 h. In subsequent plasmatic controls, level was within the optimal therapeutic range with this dose adjustment.

Mean BMI for infratherapeutic level group was 29 kg/m², while for on-range group was 25.4 kg/m². This difference was statistically significant (p = 0.0396).

For all isolated microorganisms, only two were assumed to be likely contaminants as they were isolated from the catheter entry site. Predominant isolated gender was Staphylococcus (12 cases, 54.6%), followed by Corynebacterium (6; 27.2%) and Enterococcus (4; 18.2%).

Conclusions: In more than a quarter of the cases, the optimal plasma concentrations were not achieved with the standard intraperitoneal dose of 1000 mg/96 h.

Infratherapeutic level patients had a significantly higher IMC rather than on-range patients. Staphylococcus genus was isolated in more than half of the cases.

#59

Interaction between tacrolimus and voriconazole, a case report

R. Ordorica López, Á. Cadenas Manceñido, R. C. Álvarez Cabrera, M. B. Sánchez Santiago, N. Vega Gil, M. A. Cos Cossio and M. M. Garcia Saiz

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Objective: (1) To present a clinically significant interaction between tacrolimus and voriconazole, (2) to outline the progression of the tacrolimus plasma levels and the proposed dose adjustment and (3) to describe toxicity due to this drug interaction, if applicable.

Material and/or methods: Descriptive observational case report study. The clinical information was extracted from the patient's medical record called ‘Altamira’. Therapy drug monitoring (TDM) information was obtained from departamental application ‘Modulab’, and immunoassay techniques were used.

Information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for Medicines and Medical Devices (AEMPS).

Results: We report the case of a patient who received a pulmonary transplant in 2021 and has been receiving immunosuppressive therapy with tacrolimus since then.

In February 2024, he experienced an episode of generalized musculoskeletal pain requiring bronchoscopy with transbronchial biopsy, the culture of which was positive for Aspergillus niger. The diagnosis of invasive fungal infection resulted in a hospital admission for treatment with voriconazole.

In parallel to the initiation of antifungal therapy, the tacrolimus dose was reduced by 66% to maintain plasma concentrations.

In addition, everolimus was started in combination with tacrolimus in order to keep plasma levels of both immunosuppressants within the optimal range.

Finally, once the infectious condition had resolved, treatment with voriconazole was discontinued. Therefore, it was necessary to increase the doses of both tacrolimus and everolimus in order to achieve combined plasma levels within the proposed range for the corresponding post-transplant time.

Conclusions: Monitoring plasma levels can be helpful in the management of toxicities associated with tacrolimus use. In this case, voriconazole is a potent inhibitor of cytochrome P450 and is therefore associated with increased plasma concentrations of tacrolimus.

Because this is a well-studied interaction, the dose of immunosuppressive treatment can be adjusted to prevent the occurrence of toxicity.

#61

Interaction between tacrolimus and maribavir, a case report

R. Ordorica López, Á. Cadenas Manceñido, R. C. Álvarez Cabrera, M. B. Sánchez Santiago, N. Vega Gil, M. Á. Cos Cossio and M. M. García Saiz

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Objective: (1) To present a clinically significant interaction between tacrolimus and maribavir, (2) to outline the progression of the tacrolimus plasma levels and the proposed dose adjustment and (3) to describe toxicity due to this drug interaction, if applicable.

Material and/or methods: Descriptive observational case report study. The clinical information was extracted from the patient's medical record called ‘Altamira’. Therapy drug monitoring (TDM) information was obtained from departamental application ‘Modulab’, and immunoassay techniques were used. Information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for Medicines and Medical Devices (AEMPS).

Results: In this case, we report a patient who received a bipulmonary transplant in 2021 on immunosuppressive treatment with stable tacrolimus plasma levels since then. In December 2023, she was diagnosed with cytomegalovirus infection, requiring treatment with ganciclovir. The disease was refractory to ganciclovir and was replaced by maribavir. Subsequently, a decrease in tacrolimus plasma concentration was observed, even though the dose had not changed. Therefore, suspecting a possible interaction between maribavir and tacrolimus, it was decided to discontinue the antiviral. At the same time, the tacrolimus dose was increased, and stable tacrolimus levels were again achieved.

Conclusions: Monitoring of plasma levels can be helpful in the management of toxicities associated with tacrolimus use, as well as detecting both expected and unanticipated interactions.

Initially, a possible association between maribavir and increased tacrolimus plasma concentrations has been proposed, due to the inhibitory effect of the antiviral on the P1-glycoprotein transporter. However, in our case, an unexpected interaction between maribavir and tacrolimus was observed, resulting in decreased plasma levels of the immunosuppressant.

#67

Impact of CYP2D6 genetic polymorphisms on tramadol use safety

P. Diaz Pellicer¹, A. M. Aldea Perona², M. Pérez Otero², A. Boronat Rigol¹, S. Coll Camenforte³, E. Pérez López⁴, R. De La Torre Fornell¹ and R. Ventura Alemany³

¹Human Pharmacology and Clinical Neurosciences Research Group, Hospital del Mar Research Institute, Barcelona, Spain; ²MARTrial, Hospital del Mar Research Institute, Barcelona, Spain; ³Doping Control Research Group, Hospital del Mar Research Institute, Barcelona, Spain; ⁴Hospital Universitario Virgen del Rocío, Sevilla, Spain

Objective: To describe the safety profile of tramadol use in healthy volunteers with different CYP2D6 genotypes.

Material and/or methods: CYP2D6 genotype was analysed from saliva samples in 100 healthy male and female subjects. TaqMan genotyping assays were used to determine CYP2D6 polymorphisms and copy number variations to predict final CYP2D6 activity. An estimation of 25 of them (five poor, 15 extensive or intermediate and five ultra-rapid metabolizers) were planned to be included in a phase I trial with a single dose administration of tramadol (EU CT number: 2023-503799-25-00). Oral solution of tramadol 75 mg was administrated to ultra-rapid metabolizers and 100 mg to extensive and poor metabolizers. The local institutional review board approved the study. Participants signed an informed consent.

Results: Twenty-three of the genotyped subjects were included in the clinical trial (five poor, 15 extensive and three ultra-rapid metabolizers). A total of 11 adverse events in 6 subjects were reported: nausea (4/23), dizziness (3/23), vomiting (2/23) and headache (2/23). Adverse events among different genotype groups were 3/15 extensive (19%), 1/5 poor (20%) and 2/3 ultra-rapid (67%). No serious adverse effects were recorded.

Conclusions: CYP2D6 genotype distribution observed in our group of participants aligns with those found in the general population. The reported adverse effects are described as very common (nausea and dizziness) or common (headache and vomiting) in the summary of product characteristics (SmPC). Even so, ultra-rapid metabolizers presented more adverse effects compared to poor and extensive metabolizers despite having received lower doses of tramadol. Due to the high rate of prescription of tramadol in our environment, CYP2D6 genotyping is not feasible in clinical practice. However, educating patients about possible adverse effects and close safety monitoring after the first dose could be feasible measures to identify patients that could benefit most from genotyping in order to individualize treatments.

#80

Fatal neurotoxicity associated with benzodiazepine use, a case report

R. C. Álvarez Cabrera, Á. Cadenas Manceñido, R. Ordorica López, M. B. Sánchez Santiago, N. Vega Gil and M. D. M. García Saiz

HUMV, Santander, Spain

Objective: Present a case of fatal neurological toxicity mediated by massive consumption of benzodiazepine for autolytic purposes. Evaluate the effectiveness of pharmacological interventions in the management of acute alprazolam toxicity. Identify possible factors influencing individual variability in response to alprazolam overdose.

Material and/or methods: Descriptive observational case report study. The clinical information was extracted from the patient's medical record called ‘Altamira’. Therapy drug monitoring (TDM) information was obtained from departamental application ‘Modulab’, and immunoassay (IA) techniques were used. Information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for Medicines and Medical Devices (AEMPS).

Results: A case of severe alprazolam intoxication in a young patient for autolytic purposes is analysed. The patient was admitted to the hospital in critical condition after a cardiac arrest that was successfully resuscitated, requiring admission to the intensive care unit.

Given the clinical suspicion of an autolytic drug attempt, plasma levels of alprazolam were extracted, as the patient was a regular user. These levels were extremely high, indicating a massive overdose as a result of benzodiazepine intake. Other drugs were found during the toxicological trace, although the results indicated a low concentration suggesting alprazolam as the main factor in the multiorgan failure.

Despite the advanced life support and specific treatments such as flumazenil, these measures failed to reverse the toxicity and the patient deteriorated progressively, resulting in death.

Conclusions: Monitoring of benzodiazepine plasma levels is essential in confirming massive overdose, as well as in its impact on multiorgan failure and the adequacy of therapeutic measures accordingly. Intoxication by alprazolam and other benzodiazepines can be lethal, especially in cases of massive overdose as a result of autolytic attempts. This reinforces the need for careful monitoring and regulation of benzodiazepine prescriptions, especially in patients with psychiatric conditions.

#86

Serum valproic acid levels in patients with psychiatric disorders in a tertiary care hospital: A descriptive study

P. P. Bermejo Martínez, N. Del Amo Del Arco, S. Mosquera Ferrer, I. A. Díaz Rengifo, L. Galan Caballero, T. Lahoz Hormigos, N. G. Lara Gonzalez, J. C. Rodríguez Molina, A. I. Terleira Fernandez and M. R. Salas Butrón

Hospital Clínico San Carlos, Madrid, Spain

Objective: The aim of this study was to describe the requests for serum valproic acid (VPA) monitoring in psychiatric patients, as well as the demographic characteristics, treatment dose and diagnosis.

Material and/or methods: The source of information and study population were the serum levels of VPA requested from psychiatric patients evaluated by the Clinical Laboratory Department of the Hospital Clinico San Carlos (HCSC), informed by the Clinical Pharmacology Department, from January 2022 to December 2023. VPA was measured by enzyme immunoassay.

Results: A total of 940 requests were received, of which 505 (53.72%) were female and 435 (46.27%) were male, with a mean age of 53.68 years. The most common dose was 500 mg twice daily, mainly by oral route (N = 655; 69.68%). The majority of patients were receiving chronic treatment, started over a month ago (N = 668; 71.06%). The most frequent diagnosis was bipolar and related disorders (N = 427; 45.42%), followed by schizophrenia spectrum and other psychotic disorders (N = 117; 12.44%). Of these, 25 (2.65%) were suspected of toxicity, with a mean VPA level of 57.54 μg/ml. Extraction was adequate in 342 patients (36.42%) and was performed immediately before the next dose (trough). These extractions showed a mean serum VPA level of 51.64 μg/ml, consistent with literature values.

Conclusions: There is limited evidence to establish a dosage and therapeutic range for VPA in the psychiatric population. Because of the need for correct treatment adjustment to achieve individualized, safe and effective prescribing, it is important to continue to gather information to better characterize the relationship between dose and serum concentration. This study found adequate serum VPA levels in psychiatric patients measured at the HCSC, with bipolar disorder being the most common diagnosis, followed by schizophrenia spectrum. These results are similar to those reported in the literature and may provide useful information for the safe and effective prescription of VPA in this population.

#95

Omic factors associated with adverse drug reactions to influenza vaccines

S. Salgado¹, J. Riera Arnau^1,2, E. Valencia Colorado¹, S. Mohammadi² and F. Ahmadizar²

¹Hospital Universitario Vall d'Hebron, Barcelona, Spain; ²University Medical Centre of Utrecht, Utrecht, Netherlands

Objective: Given the worldwide distribution and administration of influenza vaccines, it is important to revisit their adverse events (AEs) and their causes. Currently, omic sciences can be a powerful strategy to understand and prevent such AEs. Thus, our objective is to assess which omic factors have been studied in this regard.

Material and/or methods: A systematic review was conducted in PubMed, EMBASE, WoS and Cochrane on both published and unpublished studies up to January 2023. Studies specifically examining omic factors related to influenza vaccine adverse reactions were included. Case reports, reviews and preclinical and in silico studies were excluded.

Results: Out of 3961 screened articles, 10 addressed influenza vaccine omic factors related to AEs. Most of them were case–control designs (60%), with only two including Asian ethnicity and one including Afro-American participants. Gender distribution was balanced. Only one study addressed transcriptomic factors (such as miRNA expression), while the rest focused on genomics. Forty per cent examined febrile convulsions in relation to SCN1A, HLA, TRAJ and MBL2, among others. Additionally, 30% reviewed the association of HLA-DQB1 and HLA-DRB1 alleles with narcolepsy, identifying specific alleles like DQB1*03:02, 05:01 and 06:02 as being significantly associated. Other AEs reviewed included purpura, anaphylaxis, giant cell arteritis, sibilants and local reactions.

Conclusions: This is the first review that gathers the omic factors currently under scrutiny by the scientific community regarding influenza vaccine safety. Research on omic factors related to adverse drug reactions is crucial for preventing harm and optimizing treatment benefits. Despite the necessity for genomic testing in some treatments, its implementation remains limited. Our study supports the integration of omic research in vaccine safety.

#98

Implementation of pharmacogenetics in the Spanish Healthcare Setting for mental and cardiovascular health: BioFRAM project

L. Cañamero Garcia¹, M. Á. Seguido Rodríguez¹, S. Almenara De Riquer¹, J. M. Izquierdo Palomares², I. Fernández Esteban³, T. Sanz Cuesta⁴, A. Añino Alba³, G. P. Mejía Abril¹, J. Novalbos Reina¹ and F. Abad Santos¹

¹Hospital Universitario La Princesa, Madrid, Spain; ²Gerencia Asistencial de Atención Primaria, Madrid, Spain; ³Dirección Asistencial Centro, Gerencia Asistencial de Atención Primaria, Madrid, Spain; ⁴Unidad de Investigación, Gerencia Asistencial de Atención Primaria, Madrid, Spain

Objective: The BioFRAM project is a multicentre, observational study designed to propose the implementation of pharmacogenetics in clinical practice within the Spanish Healthcare Setting (SHS). It focuses on preventing therapeutic inefficacy and severe adverse drug reactions (ADR) in patients with mental and cardiovascular diseases.

Material and/or methods: The study includes 3500 patients from seven autonomous communities involving a variety of medical disciplines such as internal medicine, cardiology, psychiatry and primary care centres. The genetic biomarkers (gBMs) panel includes CYP2D6, CYP2C9, CYP2C19, VKORC1, SLCO1B1 and ABCG2 genes, selected for their clinical relevance and evidence (based on pharmgkb.com database) for drugs in ATC classification groups B, C and N, used in treating mental and cardiovascular diseases. In Madrid, the study expects a sample of 700 adult patients from Hospital Universitario de La Princesa (HULPr), 200 with prior pharmacogenetic testing and 500 new patients. Data related to adverse effects within 6-month post-treatment initiation will be collected.

Results: Approved by the CEIm and initiated in all participating autonomous communities, in Madrid, nine of 13 primary care centres associated with HULPr have agreed to participate. Recruitment is set to start in June 2024. Data have already been collected from 64 retrospective patients with prior pharmacogenetic testing, 36 women and 28 men. Thirty-eight patients were receiving treatment with statins, 14 with antidepressants, four with metoprolol, four with tramadol, three with antipsychotics and one with clopidogrel. By mid-2025, statistical and pharmacoeconomic results are expected to be available to draw conclusions for daily clinical practice and establish a model for implementing pharmacogenetics in the SHS.

Conclusions: BioFRAM represents a significant step towards personalized medicine. Integrating pharmacogenetics into clinical care can transform the management of mental and cardiovascular diseases, optimizing treatments and improving patient quality of life. Ongoing research and collaboration between centres are essential for the success of this initiative.

#99

Pharmacoeconomics of DPYD in fluoropyrimidine therapy: A literature review

C. Ramos del Moral, F. Lucantoni, F. Abad Santos, G. P. Mejía Abril, S. Almenara De Riquer, P. Zubiaur Precioso and L. Cañamero Garcia

Hospital Universitario de La Princesa, Madrid, Spain

Objective: Reviewing the available literature, to delimit, under pharmacoeconomic arguments, the optimal scope of implementation of DPD gene genotyping.

Material and/or methods: Integrative review of the available pharmacoeconomic studies on the genotyping of the DPYD (DPD gene) in the prescription of fluorprimidines in oncology. As databases, PubMed, Embase and Cochrane were used, in addition to studies from other sources found tangentially, available in open access in the Health Sciences Library of the Community of Madrid.

Results: After eliminating duplicates, 29 articles were screened, 12 retrieved in a full-text format, including a total of five articles in the review. Most of them were retrospective studies of DPYD genotyping vs toxicity assumption, although noticeable asymmetries were found in the way this was implied by the authors. The alleles mainly genotyped are HapB3, *13, *2A and c.2846A > T.

Conclusions: All the studies agreed that DPYD genotyping is at least, cost-neutral measure. However, the way in which this is reflected differs among them, both in the terminology used and the accuracy of the representation of the implementation scenario, demonstrating better results in the cases it resembled the most to the actual clinical practice. It is therefore necessary to carry out studies in contexts that reproduce the public health setting, with the ultimate goal of the development of standardized protocols that optimize the efficiency of the technique.

#105

Retrospective analysis of drug reactions to raltegravir associated with HLA-B*53 at the Hospital Universitario De La Princesa

C. Ramos Del Moral, P. Rodríguez Cortés, A. Barrios Blandino, F. Abad Santos, G. P. Mejia Abril, S. Almenara De Riquer, J. Novalbos Reina, M. Navares Gomez and V. Gutierrez Gomez-Lus

Hospital Universitario de La Princesa, Madrid, Spain

Objective: Our study protocol aims to assess the prevalence and characteristics of adverse reactions to raltegravir in patients carrying the HLA-B53 allele in a hospital settingas well as to describe its prevalence. Therefore, the main objective is to evaluate the existence of differences in the occurrence of adverse reactions in patients carrying this allele, with special attention to the development of DRESS (drug rash with eosinophilia and systemic symptoms) syndrome, with the ultimate goal of reviewing the usefulness of HLA genotyping prior to the prescription of raltegravir.

Material and/or methods: Medical records of patients treated with raltegravir at the Hospital Universitario de La Princesa between March 2008 and May 2020 were reviewed. Patients carrying the HLA-B53 allele were identified as well as adverse reactions (including DRESS syndrome) taking place in that time frame. Data collection includes different variables using descriptive and comparative statistics to assess the association between HLA-B53 and adverse reactions to the treatment.

Results: One hundred twenty-three patient histories were collected, 30 (24.4%) of which were female and 93 (75.6%) were male. The most prevalent allele was HLA-B*35, with a total of 22 carriers, followed by HLA-B*07, with a total of 21 carriers. Two carriers of HLA-B*53 were identified, both of which had developed DRESS. The remaining clinical–analytical information is pending analysis and is expected to be available by the end of summer.

Conclusions: This is one of the first studies of its kind on this subject, demonstrating already relevant results regarding the role of HLA genotyping prior to raltegravir use.

#109

Eslicarbazepine-related DRESS syndrome (drug rash with eosinophilia and systemic symptoms), a case report

R. C. Álvarez Cabrera, R. Ordorica López, Á. Cadenas Manceñido, M. Á. Pena Pardo, M. B. Sánchez Santiago, N. Vega Gil and M. D. M. García Saiz

HUMV, Santander, Spain

Objective: To present a case of severe cutaneous toxicity secondary to the use of eslicarbazepine, to describe the relationship between plasma levels of eslicarbazepine and its implication in the clinical presentation of toxicity and to expose the therapeutic measures for the management of toxicoderma.

Material and/or methods: Descriptive observational case report study. The clinical information was extracted from the patient's medical record called ‘Altamira’. Therapy drug monitoring (TDM) information was obtained from departamental application ‘Modulab’, and high-performance liquid chromatography (HPLC) technique was used. Information related to drugs was consulted on the drug's data sheets, depending on the Spanish Agency for Medicines and Medical Devices (AEMPS).

Results: A clinical case of DRESS syndrome with multiorgan failure in all probability related to the recent introduction of eslicarbazepine is analysed. After an ascending regimen of eslicarbazepine on the previous weeks, a patient who had not previously received the drug presented an acute skin condition, with analytical alterations and radiological findings compatible with pulmonary involvement. This is a potentially fatal adverse reaction, although rare, which has been previously described in the scientific literature. After the discontinuation of the drug and initiation of treatment with systemic glucocorticoids at high doses, the patient presented a favourable clinical and analytical evolution. The cutaneous manifestation resolved in a few days, additionally in the following weeks the multiorgan failure was corrected.

Conclusions: Treatment with systemic glucocorticoids is effective in this type of adverse drug reactions, being congruent with published literature. Early recognition and discontinuation of eslicarbazepine are crucial in preventing severe outcomes in DRESS syndrome. The case emphasizes the need for awareness among clinicians regarding the potential severe adverse effects of eslicarbazepine and the importance of therapeutic drug monitoring (TDM) in patients under treatment.

#111

Neurotoxicity associated with high plasmatic tacrolimus level and ertapenem, a case report

R. C. Álvarez Cabrera, R. Ordorica López, Á. Cadenas Manceñido, M. B. Sánchez Santiago, N. Vega Gil and M. D. M. García Saíz

Objective: To present a case of neurological toxicity mediated by tacrolimus and ertapenem, to describe the evolution of tacrolimus plasma levels and the adjustments made in the administration dose and to expose the therapeutic measures for the management of neurotoxicity.

Material and/or methods: Descriptive observational case report study. The clinical information was extracted from the clinical history records, while therapy drug monitoring (TDM) information was obtained from departmental application ‘Modulab’. Immunoanalytical techniques were used to determine these levels. The information regarding the drugs has been consulted in the technical data sheet of the Spanish Agency for Medicines and Medical Devices (AEMPS).

Results: We present the clinical case of a patient with hepato-renal transplant on regular treatment with tacrolimus, who presents acute encephalopathic symptoms in relation to the onset of endovenous antibiotherapy with ertapenem (after a pyelonephritis episode). It is described that certain drugs such as ertapenem can inhibit the elimination of tacrolimus, raising their plasma levels, increasing and enhancing the risk of neurotoxicity.

In this case, in addition to presenting clinical neurotoxicity, elevated levels of tacrolimus were analytically observed, with symptomatic improvement with the reduction of tacrolimus doses and the withdrawal of ertapenem.

Conclusions: Monitoring plasma levels can help in the management of toxicities associated with tacrolimus use. Combining ertapenem with tacrolimus may enhance neurotoxicity, highlighting the need for careful consideration and monitoring when these drugs are administered. Adjusting the dose of tacrolimus in patients with neurotoxicity, especially when other neurotoxins are associated, may contribute to the resolution of the condition.

#5

Evolution of the antidiabetic drugs use in Catalonia from 2015 to 2023

D. Wang¹ and J. A. Valles Callol²

¹Hospital Vall d'Hebron, Barcelona, Spain; ²Institut Català de la Salut, Barcelona, Spain

Objectives: To describe the antidiabetic drugs use in Catalonia from 2015 to 2023.

Material and/or methods: The consumption lists of the antidiabetic drugs during 2015–2023 period were sourced from the Catalan Health Department, utilizing daily defined doses (DDD) per 1000 inhabitants (DHD) across different Catalan territories. Excel program was used to calculate the average consumption of each individual drug and drug groups.

Results: There is a consistent annual rise in antidiabetic drugs consumption across all regions of Catalonia. Over the study period, the DHD increased (17.5%) from 68.46 to 80.42 for Catalonia as a whole.

During this time, there was a decline in the consumption of metformin alone [25.47–19.76] and sulfonylurea [13.37–8.29]. Conversely, there was a notable increase in the consumption of iSGLT2 alone [0.24–9.97], metformin with iSGLT2 [0.05–5.33] and GLP-1 [0.70–4.14]. Dapagliflozin and empagliflozin (and their combinations) were the most iSGLT2 used. Liraglutide consumption decreased, contrasted with an increase in dulaglutide and semaglutide use.

Consumption of iDPP4 increased except last 3 years [2.80–5.74]. Glinides [2.35–2.07] and pioglitazona [0.41–0.56] remained low and stable.

Insulin consumption remained stable until 2021 where a slight decrease is observed [17.74–16.70]. Glargine was the most prescribed insulin.

These trends were consistent across all territories of Catalonia, suggesting a regional uniformity in the consumption patterns of antidiabetic medications.

Conclusions: The study demonstrates an annual increase in the consumption of antidiabetic drugs, particularly notable in the iSGLT2 (alone or with metformin) and GLP-1 groups. These finding highlight the evolving landscape of antidiabetic drugs usage within Catalonia, warranting further investigation into factors driving these consumption patterns and their implications for healthcare delivery and management of diabetes.

#6

Identifying nocebo response predictors in ADHD: Insights from Metaforest algorithm analysis

M. Barcheni¹, M. Porta², D. Ramírez Saco^2,3, R. Cunill⁴, M. Farré^1,5, M. Saez^6,7, B. López⁶ and X. Castells⁸

¹Universitat Autonoma de Barcelona, Barcelona, Spain; ²Universitat de Girona, Girona, Spain; ³Hospital Universitari Vall d'Hebron Servei de Farmacologia Clinica, Barcelona, Spain; ⁴Parc Sanitari Sant Joan de Deu, Barcelona, Spain; ⁵Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; ⁶Universitat de Girona Parc Cientific i Tecnologic, Girona, Spain; ⁷Centro de Investigacion Biomedica en Red de Epidemiologia y Salud Publica, Madrid, Spain; ⁸Universitat de Girona Facultat de Ciencies, Girona, Spain

Objectives: The goal of this study is to evaluate the impact of various covariates, such as study design, the nature of the intervention and individual patient characteristics, on the nocebo response in patients diagnosed with attention deficit hyperactivity disorder (ADHD) using the Metaforest technique. Additionally, it seeks to analyse the predictive capability of Metaforest concerning the nocebo response in ADHD-related randomized clinical trials (RCTs).

Material and/or methods: This study is a secondary analysis of a previously published systematic review (Ramírez-Saco et al., 2022). The nocebo response was defined as the proportion of patients who experienced at least one adverse event while receiving a placebo. We used Metaforest to investigate moderators of the nocebo response related to the patient, intervention and study design in ADHD RCTs.

Results: A total of 105 studies were included in the analysis. The overall prevalence of patients who experienced at least one adverse event while receiving a placebo was 55.4%. However, there was substantial variability among the studies regarding the magnitude of the nocebo response, which ranged from 4.2% to 90.2%, resulting in considerable statistical heterogeneity. Notably, older patients exhibited a more pronounced nocebo response. Additionally, significant moderating effects were observed for factors such as the year of publication, treatment duration, and gender. The predictive performance of the model was found to be low-moderate (𝑅² 𝑡𝑒𝑠𝑡 = 0, 1922; 𝑀𝑆𝐸 = 0, 0408).

Conclusions: Age emerged as the most significant modifier of the nocebo response, followed by the year of publication, treatment duration and gender. However, Metaforest demonstrated limited predictive capability for nocebo responses in RCTs.

#18

Improving antibiotic prescribing in nursing homes in Spain: A before-and-after intervention study

R. Monfà Escolà^1,2, A. Garcia Sangenís^1,2,3, R. Morros Pedrós^1,2,3, J. Mateos Nozal⁴, C. Sáez Bejar⁵, C. Rodríguez Jiménez⁶, P. Matovelle⁷, E. López Pérez⁸ and C. Llor^9,3,10

¹IDIAP Jordi Gol, Barcelona, Spain; ²Cerdanyola del Vallès, Universitat Autònoma de Barcelona, Spain; ³CIBER en Enfermedades Infecciosas Instituto Carlos III, Madrid, Spain; ⁴Hospital Universitario Ramón y Cajal, Madrid, Spain; ⁵Hospital Universitario La Princesa, Madrid, Spain; ⁶Complejo Hospitalario Universitario de Canarias, Santa Cruz De Tenerife, Spain; ⁷Hospital San Juan de Dios, Zaragoza, Spain; ⁸Institut Català de la Salut, Barcelona, Spain; ⁹University of Southern Denmark, Odense, Denmark; ¹⁰Institut Català de la Salut - CAP Manso, Barcelona, Spain

Objectives: To evaluate the reduction in the inappropriate antibiotic prescribing for healthcare-associated infections among the residents and the increase in the number of hygiene activities after a multifaceted intervention.

Material and/or methods: This is a before-and-after intervention study. We performed a quality control methodology involving an evidence-based multifaceted intervention to improve care quality by implementing guidelines. The first audit, conducted prior to the intervention, took place in March–April 2023. The second audit was conducted during the same period in 2024 after the intervention. Throughout the audit periods, participants used a registration chart to record all infection-related queries.

Results: A total of 23 nursing homes completed both the first and second audit registrations. During the first audit, 1003 infections were recorded, which decreased to 789 infections in the second audit. Additionally, antibiotic prescriptions were lower in the second audit, at 79.8% compared to 88.3% in the first audit. This reduction was primarily due to a decrease in antibiotic prescriptions for respiratory tract infections, which dropped by 16% between the first and second audits. Although there was no change in antibiotic prescriptions for urinary tract infections, the incidence of these infections was lower in the second audit, at 37.6% compared to 47.4%.

Conclusions: We observed a reduction in antibiotic prescriptions after the intervention, particularly among patients diagnosed with respiratory tract infections. The intervention also successfully prevented urinary tract infections. However, there were no differences in the number of hygiene prevention procedures. Motivation is crucial for reducing inappropriate antibiotic prescriptions. A total number of 11 nursing homes were unable to complete both registrations and were excluded from the final analysis.

#28

Analysis of the activity of the pharmacy commission of a reference hospital during the period 2021–2023

M. Saldaña Valderas, M. E. Rodríguez Mateos, M. V. Manzano Martín and M. Moya Molina

Hospital Universitario Puerta del Mar, Cádiz, Spain

Objectives: To describe the requests for including drugs in the pharmacotherapeutic guide to the Pharmacy Commission of a reference hospital during the period of 2021–2023 and the decisions adopted.

Material and/or methods: The minutes corresponding to the sessions of the Pharmacy Commission held during the years 2021, 2022 and 2023 were reviewed. The number of applications (by therapeutic indication and active principle), their inclusion in the guide and the conditions of their inclusion were reviewed. The time elapsed from the date of marketing authorization reflected in the SmPC until its inclusion in the guide was also calculated.

Results: The Pharmacy Commission evaluated 42 applications of inclusion in the pharmacotherapeutic guide, corresponding to 42 indications and 39 different active principles. Three of these 42 requests were re-evaluations of drugs previously included in the guide; 93% of applications were accepted, and 7% were rejected (the three re-evaluations). The average time elapsed between authorization of the requested indication and inclusion in guide was 3.8 years. Regarding ATC codes, 51% of active principles (20/39) were classified as L group, being followed by N (13%), J (10%), V and B (8% each) and finally, A, G, H and S (around 2% each). Almost 70% of approved applications were under restricted conditions or as recommended in the therapeutic positioning report (IPT).

Conclusions: Most applications are included in the guide. The long period of time between the marketing approval and the drug inclusion is not an obstacle to access drugs since alternative mechanisms are available to allow their use, mainly the existence of a specific commission that guarantees the individualized use of drugs. The reasons for the long delay period may be diverse and require further analysis. It is essential that physicians apply for the inclusion of drugs in the guide as soon as possible to make easy and to speed up their use.

#30

Use of medicines in special conditions: Real-world treatment outcomes in a tertiary hospital

A. Giraldo Peña, M. Muñoz Bolaño, D. Rodriguez Cumplido, E. Ruiz Batuecas, M. Comas Sugranes, A. M. Ferrer Artola and R. Llop Rius

Hospital Universitari de Bellvitge, L'Hospitalet De Llobregat, Spain

Objectives: Use of medicines in special circumstances (MSC) requires individualized evaluation and follow-up to analyse effectiveness and safety. At Bellvitge University Hospital (HUB), the (CMSE) evaluates and approves applications for special use. In accordance with the CMSE's rules, prescribing physicians must complete 3- to 6-month follow-up report assessing the patient's response to treatment according to the physician's clinical judgement. The main objective was to determine the proportion of patients who presented a satisfactory response to the treatment.

Material and/or methods: A retrospective observational study of adult patients with MSC treatments authorized at HUB was performed. We included patients ≥18 years to whom drugs in special conditions were authorized from January 2020 to December 2022 and had at least 3-month follow-up information available. The type of special circumstances (unapproved indication, compassionate use or foreign medication) and the clinical response at 3–6 months (complete remission, partial response or no response) were analysed. Patients who did not start treatment or did not complete 3 months of treatment were not evaluated. The study was approved by the local Research Ethics Committee.

Results: A total of 388 applications for MSC were authorized during the study period: 320 [82%] for unapproved conditions, 44 [11%] for compassionate use and 24 [6%] foreign medication. In the 359 cases that 3- to 6-month follow-up was available, report requests were sent to doctors; 255 (71%) were received, and 237 (66%) evaluated. A complete response was observed in 175 patients (74%). In 17 (7%) cases, response was partial, and in 45 (19%), there was no response. There were 142 (60%) patients who were still on treatment at the moment of the analysis.

Conclusions: Outcome data from follow-up studies with medications in special conditions may provide useful information to improve clinical practice.

#40

Effectiveness, adequacy and costs of the antibiotic treatment in adult patients with non-cystic fibrosis bronchiectasis and primary infection by Pseudomonas aeruginosa

C. E. Delgado Espinoza^1,2, D. De La Rosa Carrillo¹, A. F. Simonetti¹, F. Gutierrez Pereyra¹, F. Cusati De Andrade¹, P. Alvarez Schlegel¹, Y. Martínez Ysasis¹, F. Sánchez Reus¹, M. J. Cortés Pestana¹ and R. M. Antonijoan Arbós¹

¹Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Barcelona, Spain

Objectives: An association has been described between infection by Pseudomonas aeruginosa (PA) and worse prognosis of non-cystic fibrosis bronchiectasis (NCFB) patients. However, studies addressed to evaluate effectiveness related to adequacy and costs of antibiotic treatment regimens are limited.

Objective: To describe effectiveness, adequacy and costs of antibiotic treatment regimens used in adults with NCFB and first or new isolation of PA in respiratory samples.

Material and/or methods: Observational retrospective single-centre study in adult patients with NCFB and PA primary infection during 2019–2021. Primary infection was considered for the first PA positive culture in sputum samples or recurrence of positive culture after 1 year. Effectiveness was determined in terms of microbiological eradication (both negative culture at 1 and 12 months). Adequate treatment was defined as the administration of appropriate antibiotic, at optimal dose, duration and at the correct route of administration. Costs of antibiotics and exacerbations management during the 12-month period after the eradication treatment were quantified. Statistical analysis using R program was performed.

Results: 53 patients were evaluated, mean age: 69.8 years (SD 10.9), 27 women (51%). Ten patients were excluded due to the absence of one or both cultures. Effectiveness was achieved in 17 of 43 patients (39.5%). Of them, adequate treatment was administered in 64.7% (N = 11). On the other hand, non-adequate treatment was administered in 69.2% of patients who did not meet the effectiveness criterion. The cost for a patient with effective treatment was €1.768,88 (antibiotic cost €102,82 and exacerbation management cost €1.666,06), whereas for a patient with non-effective treatment costs ascended to €2.381,08 (antibiotic cost €26,08 and exacerbation management cost €2.355,00) p = 0.79.

Conclusions: Effectiveness was achieved in an important percentage of studied patients who received adequate antibiotic treatment. Conversely, a lack of effectiveness was mostly observed when treatment was non-adequate. Costs due to exacerbations management were higher for patients with non-effective treatment.

#46

Use of nonsteroidal anti-inflammatory drugs in pregnant women: A descriptive study in Catalonia during the period 2011–2020

S. Mata-Ley¹, I. Soler Pérez², L. Bellas Fernández¹, M. Giner-Soriano³ and L. Camacho-Arteaga^1,2

¹Hospital Universitari Vall d'Hebron, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Barcelona, Spain; ³Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain

Objectives: The use of non-steroidal anti-inflammatory drugs (NSAID) during gestation is a concern due to potential adverse effects on both the mother and the fetus. Despite warnings, NSAID utilization during pregnancy persists. This study aims to describe NSAID prescription patterns in pregnant women in Catalonia during the period from 2011 to 2020.

Material and/or methods: An observational drug-utilization cohort study was conducted on all pregnant women with any NSAID prescriptions recorded in the SIDIAP (Information System for the Development of Research in Primary Care) database during the study period. Sociodemographic characteristics, gestational age, comorbidities, NSAID and other analgesic prescriptions, as well as pregnancy outcomes, were analysed.

Results: During the study period, a total of 76 459 women with at least one pregnancy were recorded, amounting to 99 605 gestational episodes. Of these, 16 267 had a prescription of NSAID at some point of their pregnancy. The mean age of the pregnancy women was 32.6 years (SD 6.0) with 38.5 (IQR 19.3, 40) as median duration of pregnancy episodes.

The most recorded active comorbidities in pregnant women were dermatitis and eczema (22.4%) and anxiety disorders (18.7%). Subsequently, endocrine disorders, obesity and overweight (7.9%), as well as dyslipidaemias (2.0%), were observed.

NSAID exposure was highest during the first trimester of pregnancy (15.8%), gradually decreasing as the pregnancy progressed. Ibuprofen (14.1%), naproxen (2.9%) and dexketoprofen (1.8%) were the most prescribed NSAIDs. The gestational outcomes of the exposed women were mainly vaginal delivery (59.6%), followed by abortion (25.1%) and caesarean section (14.5%).

Conclusions: NSAIDs prescription in pregnant women in Catalonia during our study period reveals their utilization despite the associated risks. These findings could be valuable in improving prescription practices and supporting clinical decision-making.

#53

Evaluation of pharmacotherapy consultations in the clinical pharmacology department of a tertiary hospital: a 5 years' experience

L. F. Castillo Lasso, M. Cortés Pestana and K. Amaro Hosey

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Objectives: To describe the main characteristics and pattern of pharmacotherapy by different sources (clinicians, pharmacists, medical societies) to the clinical pharmacology department of a tertiary hospital.

Material and/or methods: Retrospective observational study was designed to determine the frequency, services requested and final result of consultations made over the period from January 2019 to April 2024. Clinical queries were received through a variety of channels (telephone, email, formal and curbside consultation). The variables recorded included the means by which contact was made, origin and type of the query, number of drugs involved, medical specialty of the inquiring healthcare professional, population involved and query categories (general information, adverse drug reaction and patient-specific queries, respectively). Descriptive statistical analysis using Stata 17 Basic Edition program was performed.

Results: During the study, a total of 110 consultation requests were documented. The year with less consultation requests was 2020 due to COVID pandemic (13) and has increased reaching a peak in 2023 (24). Moreover, a decreasing tendency of curbside consultations has been observed at the expense of an increase in email and formal contact. The leading consultants have been hospital staff physicians, mainly from allergology and gastroenterology, as well as medical societies and institutions. Drug assessment in patient-specific queries and drug information requests have been the main topics (51 and 46 cases, respectively), followed by ADR assessment and notification (13). The majority of consultation requests involved one single drug (82), and only in few cases, they were related to specific populations such as pregnant women or children.

Conclusions: Clinical pharmacologist must be part of patient care, providing a useful tool to physicians in order to help in treatment guidance, offering drug information and adverse drug reaction assessment. The promotion of this activity is essential to publicize the role of clinical pharmacology and to and demand a greater presence in healthcare practice.

#55

A descriptive study on the prescription of monoclonal antibodies against the calcitonin gene-related peptide pathway for refractory migraine in a tertiary hospital

I. A. Díaz Rengifo, N. G. Lara Gonzalez, T. Lahoz Hormigos, L. Galán Caballero, S. Mosquera Ferrer, P. P. Bermejo Martínez, J. C. Rodríguez Molina, J. A. Peña Pedrosa, L. Laredo Velasco and M. García Arenillas

Hospital Clínico San Carlos, Madrid, Spain

Objectives: Monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP) for the prophylaxis of refractory migraine are currently restricted in terms of funding. This study aims to describe the prescription trend of anti-CGRP in refractory migraine population of the San Carlos Clinical Hospital in Madrid between January 2020 and December 2023.

Material and/or methods: A retrospective study was conducted to review the number of anti-CGRP prescriptions requested through the Institutional Commission for Access to Special Use Medication, which regulates its institutional use by approving all the prescriptions.

Results: A total of 785 new prescriptions were made for one of the available anti-CGRP, representing 586 patients treated for any type of refractory migraine. The majority of prescriptions (n = 252) were made in 2023 (32.1% of the period prescriptions), followed by 208 in 2021, 176 in 2020 and 149 in 2022.

At the time of prescription, the mean age was 48.7 years (SD ± 12.7) and 88.03% of patients were women. Of the 785 prescriptions, 40.13% were galcanezumab, 28.15% erenumab, 23.57% fremanezumab and 8.15% eptinezumab. A shift in prescribing patterns was observed over the years. In 2020, 61.36% of the prescriptions were for galcanezumab, 37.5% for erenumab and 1.14% for fremanezumab. By 2023, the distribution had changed to 26.59% for galcanezumab, 20.63% for erenumab, 27.38% for fremanezumab and 25.4% for eptinezumab.

Of the 586 patients, a total of 172 (29.35%) switched their initial anti-CGRP prescription to another one during the evaluated 4 years; 146 switched once, 25 switched twice, and one switched three times.

Conclusions: The majority of prescriptions were for women and galcanezumab was the preferred drug during the study period. The observed trend in prescription may be related to the market availability of newer options, like eptinezumab recently approved in 2022; therefore, a shift could be expected in the future. A relevant proportion of patients switched to another available anti-CGRP treatment alternative.

#56

Can artificial intelligence tailor the treatment of complex patients? The use of TDApp for drug recommendations in ADHD complex patients compared to the Spanish ADHD guideline

I. Darnaude Ximénez¹, E. Baykova², D. Ramírez Saco³, C. Lombardía⁴, D. Serrano⁵, R. Cunill⁶, Ò. Raya⁷, B. López⁷ and X. Castells⁸

¹Clinical Pharmacology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain; ²Child and Juvenile Mental Health Centre Selva Marítima, Institut d'Assistència Sanitària, Blanes; Institut d'Investigació Biomèdica de Girona, Mental Health and Addictions Research Group, Girona, Spain; ³Department of Clinical Pharmacology, Vall d'Hebron Barcelona Hospital Campus, Barcelona; TransLab Research Group, Department of Medical Sciences, University of Girona, Barcelona, Spain; ⁴Child and Juvenile Mental Health Centre Gironès – Pla de l'Estany, Institut d'Assistència Sanitària, Girona, Spain; ⁵Acute Psychiatry Hospitalization Service, Parc Hospitalari Martí i Julià, Institut d'Assistència Sanitària, Salt; Institut d'Investigació Biomèdica de Girona, Mental Health and Addictions Research Group, Salt, Girona, Spain; ⁶Acute Patients Unit, Parc sanitari Sant Joan de Déu Numància, Barcelona, Spain; ⁷Control Engineering and Intelligent Systems (eXiT), Department of Electrical, Electronic and Automatic Engineering, University of Girona, Girona, Spain; ⁸TransLab Research Group, Department of Medical Sciences, University of Girona, Girona, Spain

Objectives: To compare treatment recommendations for attention deficit hyperactivity disorder (ADHD) patients between TDApp and the Spanish guideline, considering patient complexity.

Material and/or methods: A prospective cohort study was conducted on 26 ADHD patients. TDApp, an artificial intelligence (AI)-based recommender system, involves patients and families in ADHD treatment decisions. It integrates both patient and clinician preferences regarding symptoms to be treated and adverse effect to be avoided and then generates tailored recommendations based on available evidence.

We evaluated the similarity between TDApp's recommendations and the Spanish ADHD guideline by establishing a pharmacological ‘distance’ using the Neuroscience-based Nomenclature classification system, ranging from 0 (identical recommendations) to 3 (completely different). Complexity was defined as having a chronic psychiatric comorbidity and/or an ADHD severity score ≥45 in the ADHD Rating Scale-5.

Results: The study included 26 patients (mean age 12.1 years, 58% male), divided into ‘complex’ (n = 13) and ‘non-complex’ (n = 13).

The average distance from the guidelines was 1.95 (95% CI 1.59–2.05), and ‘complex’ patients showed a greater distance than ‘non-complex’ ones (2.27 [95% CI 1.85–2.69] vs. 1.62 [95% CI 1.19–2.05], p-value 0.048). The guidelines provided the same four treatment recommendations for all patients, except in four complex patients who were limited to two alternatives due to contraindications. In contrast, TDApp offered 0–8 alternatives, averaging 2.15 options per patient (0.85 in complex patients and 3.5 in non-complex ones).

This difference is partially attributed to TDApp recommending no treatment for 46% of complex patients, compared to 23% of simple patients, possibly because of lacking scientific evidence for generating ad hoc recommendations for these patients.

Conclusions: AI-based recommender systems, like TDApp, are promising technologies that can complement traditional guidelines. Nevertheless, prudence is advised, particularly in complex patients.

#65

Comprehensive analysis of heart failure: Characteristics, treatment and outcomes in a reduced ejection fraction patient cohort from SIDIAP database, Catalonia, Spain

R. Monfà^1,2, M. Giner-Soriano^1,2, S. Fernández-García^1,2,3, A. Vallano^4,2,5, R. Vives^4,2 and R. Morros^1,2,5

¹Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; ²Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; ³Universitat de Girona, Girona, Spain; ⁴Medicines Department, Catalan Healthcare Service, Barcelona, Spain; ⁵Institut Català de la Salut, Barcelona, Spain

Objectives: We aimed to analyse characteristics, treatments and hospital admissions and all-cause mortality within a cohort of patients with HFrEF in PHC, focusing on sex and gender differences.

Material and/or methods: Population-based cohort study including adults diagnosed with HFrEF in PHC from 2018 to 2022. The data source was the Information System for the Development of Research in Primary Care (SIDIAP). We analysed information on sociodemographic and clinical characteristics, exposure to drugs for HF treatment, hospitalizations due to HF and all-cause mortality.

Results: We included 17 169 HFrEF patients: 59.5% men and 40.5% women. We found differences between men and women in clinical characteristics, also in the drug combinations. Suboptimal use of adherence to guideline-directed medical therapy (GDMT) was observed, but men received more drugs than women. Women had higher hospital admission (44.6% vs. 42.1%) and all-cause mortality (27.2% vs. 25.3%). The hazard ratio of hospitalization was higher in older than 60, with increasing NYHA, diabetic patients and in previously hospitalized.

Conclusions: We observed sex disparities in the baseline characteristics. Also pharmacological treatment for HFpEF showed variations, with differences in drug use, combinations and adherence to GDMT. Women demonstrated higher rates of hospital admissions and all-cause mortality. These findings highlight important sex- and gender-related distinctions in HFrEF in routine clinical practice.

#66

Urinary tract infections in women: Trends in antibiotic treatment over 10 years in Catalonia, Spain

S. Fernández García^1,2,3, A. Moragas Moreno^4,1,5, M. Giner Soriano^1,2, C. Llor^1,5, A. Resa Campos⁶, D. Ouchi¹, A. García Sanguenís¹ and R. Morros Pedrós^1,2,5

¹Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; ²Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; ³Universitat de Girona, Girona, Spain; ⁴CAP Jaume I, Tarragona, Spain; ⁵CIBER de Enfermedades Infecciosas, Instituto Carlos III, Madrid, Spain; ⁶Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola Del Vallès), Spain

Objectives: The aim of our study was to describe the antibiotic treatment of urinary tract infections (UTIs) in adult women during 10 years in primary health care (PHC) in Catalonia.

Material and/or methods: It was a population-based observational cohort study between 2012 and 2021 using different local databases with information on clinical practice in PHC. The main database was SIDIAP that contains pseudonymized clinical information from electronic health records in PHC for 80% of the Catalan population. UTIs included cystitis and pyelonephritis according to the ICD-10 codes. The evolution of UTIs and its antibiotic prescriptions was described using typical summary statistics.

Results: A total of 103 148 UTIs were recorded in 2012, increasing to 290 915 episodes in 2021, with no increase in the mean age of the patients (around 55 years). The most frequent diagnoses were dyslipidaemia (30.61%) and diabetes mellitus (13.26%). Urinary lithiasis remained stable (around 6.66%). Chronic renal failure increased from 4.30% to 9.56%. 87.84% of the patients had at least one antibiotic treatment recorded during the UTI episode, and 24.03% were treated with a combination of 2 or more antibiotics. Fosfomycin was the most commonly recorded treatment during the study period (39.92% in 2012 and 66.78% in 2021). Quinolones were the second most common treatment, with their registration decreasing over the study period (17.74% in 2012 and 7.05% in 2021). Only 12.16% did not record any antibiotic treatment.

Conclusions: The number of UTIs has increased over the last 10 years, as the use of fosfomycin. Recording of UTIs in electronic health records has improved. One of the reasons for the increased in diagnoses recorded might be that linking antibiotic treatment to a suspected bacterial infection is now mandatory in our setting. The increase of fosfomycin as an antibiotic treatment is in line with local clinical guidelines for the treatment of uncomplicated UTIs.

#69

Access to medicines in special situations: Overcoming the challenges for the individualized access

J. Porcel Maleno¹, G. Ronda Roca¹, C. Payares Herrera¹, A. Sancho López¹, L. Delgado Tellez De Cepeda² and C. Avendaño Solá¹

¹Department of Clinical Pharmacology, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain; ²Department of Pharmacy, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Spain

Objectives: Standard access to medicines comprises several decisions based on the average/prototype patient. Treatment individualization may require using medicines in special situations (MSE), early access to non-authorized or not publicly funded medicines, through ‘individualized’ approval involving local/regional authorities. Equitable/justified NHS access must be ensured for exceptional cases, as well as a streamlined procedure. Focus must be on the pathways, not on individual cases (i.e. committee discretional opinion). A transparent procedure with well-established criteria should be used for individual decisions, accepting that different individuals receive different decisions, but according to the same judgement standard.

Aim: Presenting the experience of a clinical pharmacology department (CPD) in a tertiary hospital on implementing an access procedure for individual MSE requests.

Material and/or methods: Physicians send a medical consultation to CPD and a request to the pharmacy, which will issue independent reports to the medical director, who makes the decision. CPD advice (uploaded at the patient medical record) is based on established criteria including justification of the individual exception, clinical need for treatment, need for early access and criteria to assess treatment benefit. On-year retrospective analysis of requests is presented.

Results: One hundred eighty-six applications were identified, 45% from oncology; 13 departments sent at least one request. Most frequent: pending P&R (34.4%), non-authorized (19.4%), non-reimbursed medicines (10.2%). One hundred sixteen reports were requested to CPD (86% favourable opinions). Non-favourable opinions were due to identifying available alternatives or benefit uncertainties. Sixty-eight applications were directly approved (without CPD report), due to urgency (16%), pre-existing access protocol (25%), no cost (19%), unknown reasons (40%). 86/116 (74.14%) applications with CPD reports were granted local access.

Physicians provided positive feedback on the MSE procedure, recognizing it is reassuring for their medical decisions.

Conclusions: Implementing a well-established access procedure is paramount to guarantee a fair, harmonized/justified access to MSE. CPD involvement provides support to physicians' requests and individualized, readily available alternatives while ensuring that management decisions are backed by legally-sound bases.

#73

Drug utilization study in a cohort of migraine patients from SIDIAP database, Catalonia, Spain

R. Monfà^1,2, A. García-Sangenís^1,2, S. Fernández-García^1,2,3, R. Bonilla^1,2, R. Morros^1,2,4 and M. Giner-Soriano^1,2

¹Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; ²Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; ³Universitat de Girona, Girona, Spain; ⁴Institut Català de la Salut, Barcelona, Spain

Objectives: To analyse characteristics, acute and preventive treatments within a cohort of patients with migraine in primary health care (PHC), focusing on sex and age differences.

Material and/or methods: Population-based cohort study including adults with migraine diagnosis or receiving treatment for acute migraine but without diagnosis registered from January 2018 to June 2023. The data source was the Information System for the Development of Research in Primary Care (SIDIAP). We analysed information on sociodemographic and clinical characteristics and exposure to preventive and acute drugs (antimigraine drugs, analgesics and non-steroidal anti-inflammatory drugs [NSAID]) for migraine.

Results: We included 362 152 patients: 79.9% were diagnosed with migraine and 20.1% received an acute specific treatment for migraine (N02C ATC) without having a diagnosis registered in the electronic health records. Female sex was more frequently represented in comparison with male sex (75.9% vs. 24.1%). Sumatriptan, zolmitriptan and rizatriptan were the most common specific acute treatments prescribed with annual number of DDD considerably higher in women and people older than 65 years. Paracetamol was used by 52.5% of patients. Among the NSAID, ibuprofen, naproxen and dexketoprofen were the most used. Amitriptyline was the most prescribed preventive treatment, especially in women, followed by flunarizine, propranolol and topiramate.

Conclusions: We observed sex disparities in the baseline characteristics and in the treatment, with higher rates of drug use and higher rates of DDD in women. These differences increased with ageing. Several migraine preventive treatments are used. The main limitation is the lack of linkage between diagnoses and prescriptions, affecting analgesics, NSAID and preventive treatments, which might be used for different indications than migraine. These findings highlight the importance of further studies to determine the best way to treat and especially to prevent migraine. In that sense, IDIAPJGol has started in 2024 the PREMI clinical trial (EU CT Number: 2024-513597-22-00).

#77

Regulatory features for precision oncology medicines authorized by the EMA

G. Puig Comas^1,2, C. Sans Pola^3,2, I. Danés Carreras^3,2, C. Pontes Garcia^4,2, M. Umbria Vivancos¹, N. Puñet Valls^1,2, M. Gasol Boncompte^1,2, J. M. Fontanet Sacristan^1,2 and A. Vallano Ferraz^1,5,2

¹Catalan Health Service, Barcelona, Spain; ²Autonomous University of Barcelona, Barcelona, Spain; ³Vall d'Hebron University Hospital, Barcelona, Spain; ⁴Santa Creu i Sant Pau Hospital, Barcelona, Spain; ⁵Catalan Health Institute, Barcelona, Spain

Objectives: Targeted therapy precisely identifies and selectively affects only abnormal proteins as biomarkers driven by genetic mutations in cancer cells. Few studies have evaluated the characteristics associated with the regulatory approvals of these medications in European Union (EU). The aim of this study was to assess the regulatory features and considerations related to this class of treatments.

Material and/or methods: We conducted an observational, retrospective study including precision oncology treatments for solid tumours authorized by the European Medicines Agency (EMA) from 2015 to 2023. Information on medicines, tumour type, target, clinical trial characteristics and approval procedures was collected from the EMA website.

Results: From 2015 to 2023, there were 36 authorized precision oncological medicines (six orphan) for 39 different indications. Sixteen (41%) indications were for first line treatments and 23 (59%) were for second and subsequent lines. Non-small cell lung cancer (38%) and breast cancer (20%) were the most frequent neoplasms. Eighteen distinct molecular targets were evaluated, with the most frequent being BRAF V600 mutations (15%) and HER-2 (12%). There were 43 main clinical trials assessing the efficacy of those medicines: 18 (46%) were phase II, 20 (51%) were not randomized, 29 (74%) were not blinded, and 23 (59%) did not have a control group. The approval procedure was accelerated or PRIME in six and two authorizations, respectively. The median time of authorization was 427 days (range 140–799), and the authorization was conditional in 15 (38%).

Conclusions: This study provides an overview of the regulatory features and considerations associated with the approval of precision oncology treatments for solid tumours in the EU. Our findings highlight the diversity of target biomarkers, the lack of randomization and control groups in clinical trials, and targeted therapy authorization was frequently conditional. These insights provide valuable information about the regulatory decision-making process on treatments for patients with cancer.

#85

Experiences prescribing medicines, alternative treatments and vaccines among health professionals in Catalonia (Spain): A qualitative study

B. Munné-Barellas^1,2, A. García-Egea^1,3, R. Morros-Pedrós^1,4,5, C. Vedia-Urgell⁶, M. Giner-Soriano^1,2 and L. Medina-Perucha^1,3,7

¹Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAP-JGol), Barcelona, Spain; ²Universitat Autònoma de Barcelona, Bellaterra, Spain; ³Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain; ⁴Universitat Autònoma de Barcelona, Bellaterra, Bellaterra, Spain; ⁵Institut Català de la Salut, Barcelona, Spain; ⁶Unitat de Farmàcia, Servei d'Atenció Primària Barcelonès Nord i Maresme, Badalona, Spain; ⁷Network for Research on Chronicity, Primary Care and Health Promotion (RICAPPS), Barcelona, Spain

Objectives: To explore beliefs and experiences prescribing medicines, alternative treatments and vaccines among primary healthcare (PHC) professionals in pregnant breastfeeding women and people in Catalonia, Spain.

Material and/or methods: Three discussion groups with 21 PHC professionals were conducted in three PHC centers (one in a rural area and two in urban areas) in Catalonia during February 2024, with a critical and gender-based perspective. Sampling was intentional, recruiting participants through key contacts in PHC and the research team. Data were analysed using thematic analysis.

Results: Participants' narratives focused on how professionals perceive and face the changes in the professional-user relationship and how they work towards shared decision-making to manage medication and vaccination prescriptions. Besides, difficulties prescribing among the pregnant and breastfeeding population were discussed, particularly for GPs. Midwives and gynaecologists emphasize the importance of monitoring before and after pregnancy to ensure good medication management and the importance of coordinating between specialists in PHC for acute and chronic conditions (e.g. mental health). Finally, participants highlighted challenges regarding medication management due to the increasing use of private healthcare and alternative treatments by pregnant and breastfeeding women.

Conclusions: Based on participants' narratives, there is the need to strengthen continuous training in shared-decision making approaches and improve resources to facilitate prescribing decisions, for instance, through the availability of online portals to check medicine safety and the improved coordination and consultations between PHC professionals.

#94

Analysis of new medicine approvals in the European Union: A 5-year review of the CHMP

T. Lahoz Hormigos¹, S. Rodríguez Soriano², I. A. Díaz Rengifo¹, P. P. Bermejo Martínez¹, L. Galán Caballero¹, S. Mosquera Ferrer¹, N. G. Lara González¹, J. C. Rodríguez Molina¹, L. Laredo Velasco¹ and E. Vargas Castrillón¹

¹Hospital Clínico San Carlos, Madrid, Spain; ²Roche Farma, Madrid, Spain

Objectives: This study aims to analyse the registration of new medicines approved by the European Medicines Agency (EMA) over the last 5 years, based on the reports of the Committee for Medicinal Products for Human Use (CHMP).

Material and/or methods: A retrospective review of CHMP reports available on the EMA website was conducted from 1 January 2019 to 31December 2023. Relevant data were extracted for each approved medicine, including therapeutic area, medicine type and approved indications.

Results: Of the 436 new medicines evaluated, 419 (96.1%) received a positive opinion, and 17 (3.9%) received a negative opinion. Among the medicines with a positive opinion, 270 (64.4%) were new medicines, of which 105 were orphan medicines and 165 were non-orphans medicines. Of the other 149 approved medicines, 79 (18.9%) were generics, 40 (9.5%) were biosimilars, 21 (5%) were hybrids, and 7 (1.7%) were under informed consent. In addition, two vaccines for preventing COVID-19 infection (0.5%) received a positive recommendation through an extraordinary procedure. The distribution of medicines evaluated by therapeutic area was as follows: oncology 19.5% (85), neurology 11.7% (51), haemato-oncology 9.2% (40), endocrinology 8.9% (39), infectious diseases 7.3% (32) and haematology 7.1% (31), among others. The most common indications for medicines with positive opinions were multiple sclerosis (17), diabetes mellitus (16), multiple myeloma (16), breast cancer (14) and COVID-19 (12).

Conclusions: The European Union medicines approval system, through the CHMP, has achieved a high rate of positive opinions for new medicines over the last 5 years. Oncology and neurology have benefited the most, reflecting the adaptation of the regulatory system to current public health needs, including chronic and disabling diseases. This analysis could serve as a basis for future research and regulatory adaptations.

#107

A retrospective cohort study on response to biologic medications in obese patients with moderate to severe psoriasis in a third-level hospital

J. Riera Arnau^1,2, D. Wang^1,2, J. Mollet Sánchez^1,2, L. Bellas Fernández^1,2, R. Boy¹, V. García-Patos Briones^1,2, G. Aparicio Español^1,2, E. Ballarín Alins¹ and M. Sabaté Gallego^1,2

¹Hospital Universitari Vall d'Hebron, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Barcelona, Spain

Objectives Psoriasis is a chronic inflammatory skin disease frequently associated with metabolic disorders. Obesity exacerbates inflammation and is presumably related to worse treatment response. Moderate-to-severe cases often require biological systemic treatments. Our aim was to describe the number of biological treatment lines needed to achieve an optimal clinical response, that is, a Psoriasis Area Severity Index (PASI) < 3, the duration of use of each biological drug and the reasons for discontinuation.

Material and/or methods: We performed an observational study on patients with moderate-to-severe psoriasis (baseline PASI ≥ 10) and a BMI ≥ 30 kg/m² who started a biological treatment between July 2007 and December 2022. Data were sourced from a third-level hospital registry.

Results: The study included 58 patients, 58.6% men, with a median BMI of 35.9 [range: 30.5–47.8] kg/m². The total contribution of 390.1 person/years. Notably, 77.6% (45 patients) achieved a PASI < 3. Among the respondents, the median number of treatment lines used was of 2 [range: 1–5], and the median response time of 2–7 months. Etanercept, adalimumab and ustekinumab were the most used biologicals using standard dosages. None of the study patients needed treatment intensifications. The median exposure time to any biological treatment was 80 months, slightly higher for those achieving optimal clinical response (88 months). Over 85% of first-line biological treatments were discontinued due to secondary (over 60%) or primary (over 10%) lack of effectiveness, a trend consistent across treatment lines.

Conclusions: The achievement of optimal response in our cohort was similar to findings in the previous literature on the general population. Long-term exposure to such medicines does not seem to be associated with significant toxicity, but rather with a gradual decrease in response, leading to a switch in treatment. We hope this project helps generate evidence for medicine use in a scarcely studied subpopulation in this setting.

#108

Calcineurin inhibitors as treatment in lupus nephritis, a bibliographic review

R. Ordorica López, R. C. Álvarez Cabrera, Á. Cadenas Manceñido, M. B. Sánchez Santiago, N. Vega Gil and M. M. García Saiz

Hospital Universitario Marqués de Valdecilla, Santander, Spain

Objectives: To explain what lupus nephritis is, to present the therapeutic algorithm for lupus nephritis and to justify the use of calcineurin inhibitors in the treatment of lupus nephritis.

Material and/or methods: Systematic review of scientific articles by consulting the MedLine and PubMed databases, in the last 10 years, in Spanish and English. No restrictions were made regarding the type of study. We reviewed abstracts and, where necessary, the complete articles, finally taking into account all the articles that included recommendations on the treatment of lupus nephritis and eliminating the rest.

In addition, the consensus document of the Spanish Society of Nephrology for the diagnosis and treatment of lupus nephritis was reviewed.

Results: Lupus nephritis is commonly classified after renal biopsy according to the morphological changes observed into six classes. This classification is necessary to decide the therapeutic approach to be followed. All patients with lupus nephritis, regardless of stage, should start treatment with hydroxychloroquine, except when contraindicated. Preventive treatment of risk factors that may cause progression to chronic kidney disease (statins, angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists) should be associated. The treatment of this disease includes an induction phase and a maintenance phase using immunosuppressive and non-immunosuppressive therapies.

Immunosuppressive therapy is used in the induction phase of class 3, 4 and 5 lupus nephritis. However, in the maintenance phase, it is usually reserved for patients in class 5.

Conclusions: Although treatment with calcineurin inhibitors is largely related to immunosuppressive therapy used in transplantation, the usefulness of these drugs goes much further. In the case of lupus nephritis, in addition to tacrolimus and cyclosporine, there is the possibility of using voclosporin. This drug is a cyclosporine analogue that is more effective, has fewer side effects and does not require monitoring of plasma levels.

#110

European Medicines Agency's (EMA) conditional marketing approvals (CMA): A 2006–2023 overview

L. Arellano^1,2,3, P. Alcubilla^1,2,3 and L. Leguízamo^1,2

¹Hospital Clinic de Barcelona, Barcelona, Spain; ²Institut D'investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; ³Universitat de Barcelona, Barcelona, Spain

Objectives: CMA granted by EMA allows early approval based on less complete clinical data than normally required, prioritizing earlier patient access and fulfilling unmet medical needs. CMAs are valid for 1 year, renewable annually, or can be converted to full marketing authorization (FMA). In a previous analysis from 2006 to 2020 (EACPT 2022), we found that anticancer therapies are frequently granted a CMA, usually based on one pivotal clinical trial (PCT), with a median time to FMA just under 5 years. Our hypothesis is that recent years show an increasing trend in CMA granting and quicker conversion to FMA. The aim is to analyse medicines granted CMA from 2006 to 2023 focusing on initial authorization, time to FMA and compare previous years (2006–2019) to the latest (2020–2023).

Material and/or methods: Publicly available initial marketing-authorization documents from EMA's website were reviewed to extract changes made since initial CMA, drug types and PCT characteristics. Cut-off date: 23 May 2024.

Results: From 2006 to 2023, 89 drugs received CMA: 46 from 2006 to 2019 and 43 from 2020 to 2023. Most frequent drugs were antineoplastics/immunomodulators (56, 63%) and anti-infectives or antivirals for systemic use (17, 19.1%). Most CMAs were based on one PCT (66, 74.15%), with 47 (71.2%) for haemato-oncology drugs and ORR as primary endpoint (42, 89%). Changes in authorizations included FMA (44, 49.4%), CMA renewal (28, 31.4%), revocation (2, 2.3%), non-renewal by European Commission (1, 1.1%), withdrawn by holder (4, 4.5%) and no data available (10, 11.2%). The median time to FMA was 31.7 months (2.61 years); from 2006 to 2019: 37.13 meses (3.09 years) and from 2020 to 2023: 23.58 meses (1.96 years).

Conclusions: In the past 4 years, the number of CMAs granted nearly matched that of the preceding 13 years, with quicker conversion to FMA. Anticancer medicines, typically based on one PCT with ORR as primary endpoint remain the standard for granting CMAs.

#9

A multidisciplinary team intervention in nursing homes in Catalonia: The role of a clinical pharmacologist

E. Anderssen Nordahl^1,2,3, M. Sabaté Gallego^1,2,3, M. Bosch Ferrer^1,2,3, E. Fernández Liz^4,5 and M. E. Barceló Colomer^4,5

¹Clinical Pharmacology Service, Vall d'Hebron University Hospital, Barcelona, Spain; ²Clinical Pharmacology Group, Vall d'Hebron Research Institute, Barcelona, Spain; ³Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain; ⁴Primary Health Care Barcelona, Management of Primary Care and the Community of Barcelona City, Catalan Institute of Health, Barcelona, Spain; ⁵Foundation University Institute for Research in Primary Health Care Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain

Objectives: To describe a systematized medication review implemented in institutionalized patients by a multidisciplinary team, including a clinical pharmacologist.

Material and/or methods: The Catalan Institute of Health (ICS) promotes medication review in nursing homes. The standard used to establish if drugs were considered potential medication-related problems (MRPs) was the support tools Self-Audit and PREFASEG and the list of potentially inappropriate medications proposed by ICS.

Results: The intervention consisted of reviewing the medication plans, detecting MRPs and developing an improvement plan. For this purpose, a multidisciplinary team was created, which included general practitioners, nurses, social and administrative workers from primary care, clinicians and nurses from nursing homes, a clinical pharmacologist and a clinical pharmacist. The clinical pharmacologist acted as the coordinator of the multidisciplinary team and actively reviewed all the medications and made recommendations, considering the age and comorbidities of the patients. These entailed (a) completing absent data; (b) withdrawing a drug when MRPs were considered: potential DDI, duplicated therapies, contraindicated drugs, inappropriate drugs or drugs of doubtful efficacy; (c) appropriateness of drug therapy due to the need to reduce the dose, a bad tolerance, to reduce the anticholinergic load or a high risk of ADRs; (d) substitute a drug owing to considering other drugs as a first choice or equivalent drugs.

Conclusions: The designed intervention highlights the importance of multifaceted interventions in nursing homes, including patient-centred approaches, interdisciplinary collaboration and technology-driven solutions. The inclusion of a clinical pharmacologist in a multidisciplinary team ensures proper pharmacological review in nursing homes. The logistical aspects of coordinating a multidisciplinary team, ensuring effective communication and addressing potential conflicts in treatment plans require careful management.

#27

The Comptagotes, a newsletter on pharmacotherapeutic updates in primary care: What do we publish?

M. E. Barceló Colomer¹, J. A. Vallès Callol¹, E. Fernández Liz¹, G. Bendahan Barchilon¹, S. E. Mata Ley², D. Wang², A. Troncoso Mariño¹, A. Larripa Torras¹, R. Riel Cabrera³ and C. Carbonell Abella³

¹Àrea del Medicament i Servei de Farmàcia, Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Barcelona, Spain; ²Servei Farmacologia Clínica, Hospital Vall d'Hebron. Barcelona, Institut Català de la Salut, Barcelona, Spain; ³Gerència d'Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Barcelona, Spain

Objectives: Since its inception in 2012, Comptagotes has been a trusted bimonthly newsletter dedicated to primary health care (PHC) professionals. Our mission is to enhance the therapeutic skills of practitioners by providing meticulously curated and critically analysed pharmacotherapeutic updates. Our editorial board, composed of expert clinical pharmacologists and pharmacists, rigorously reviews 20 leading journals in the field. They handpick, summarize and critically evaluate the most relevant articles, ensuring our readers receive the highest quality information to support their practice. The magazine is published in electronic format and is distributed via email and social networks.

Material and/or methods: This descriptive study characterizes the summaries published in Comptagotes, focusing on various aspects such as the types of studies, themes, health problems and drugs discussed.

Results: From September 2012 to March 2024, 72 issues and 365 articles were published, averaging five articles per issue (range: 3–11). Summaries were created by 31 contributors. In 135 (37%) of the abstracts, more than two bibliographic sources were cited. The types of studies include 63 (17%) meta-analyses, 49 (13%) clinical trials, 42 (12%) cohort studies, 36 (10%) narrative reviews, 19 (5%) case–control studies and 32 (8%) other studies; 124 (33%) summaries included more than one study type. The priority topics were safety (221, 61%), efficacy (109, 30%) and effectiveness (31, 8%). The most discussed drugs were B01 antithrombotic agents (17%), A10 diabetes medications (15%), N02 analgesics (10%), N06 psychoanaleptics (9%), N05 psycholeptics (6%) and C10 lipid modifiers (5%). Twenty-nine other drug types (39%) were also covered, while 50 publications mentioned no specific drug. The most frequently referenced diseases in 325 summaries were circulatory (22%), endocrine/metabolic (16%), injury/poisoning (12%), respiratory (8%), mental/behavioural (6%) and nervous system (6%). Eighty-five summaries (23%) focused on specific population groups, mostly the elderly (39%).

Conclusions: Professionals seek quick-access, agile tools to stay therapeutically updated.

#31

Extended use of N-acetylcysteine perfusion in acute acetaminophen intoxication: A case report

P. P. Bermejo Martínez, I. A. Díaz Rengifo, L. Galán Caballero, S. Mosquera Ferrer, T. Lahoz Hormigos, N. G. Lara Gonzalez, J. C. Rodríguez Molina, A. I. Terleira Fernández and M. R. Salas Butrón

Hospital Clínico San Carlos, Madrid, Spain

Objectives: This case report aims to highlight the role of extended N-acetylcysteine (NAC) perfusion in treating acute acetaminophen intoxication.

Material and/or methods: A clinical review of a 24-year-old female patient diagnosed with a acetaminophen overdose was conducted. Acetaminophen serum levels were measured on an automated analyser, the Indiko Plus® (Thermo Fisher).

Results: We report a case of acetaminophen overdose in a 24-year-old female who was brought to the emergency department with decreased level of consciousness. The ingested dose and the time of ingestion were unknown. Initially, liver and kidney functions were abnormal: alanine transaminase (ALT) 235 mg/dl, aspartate transaminase (AST) 163 mg/dl, creatinine 1.02 mg/dl and GRF 77 ml/min. A venous blood gas analysis revealed metabolic acidosis and hyperlactacidemia. The serum acetaminophen level was at 220 μg/ml. After 3 h, the concentration reduced to 177.7 μg/ml, suggesting a slowed metabolic clearance, predictive of hepatotoxicity. The patient received IV NAC, administered for 36 h. The NAC infusion was discontinued despite the elevated liver transaminase (ALT 335 IU/L and AST of 202 IU/L) and prolonged international normalized ratio (INR), after which liver enzymes continued to rise, peaking at ALT 10814 IU/L and AST 7567 IU/L, with an increase in the INR (2.9) and decreased level of consciousness, suggesting an acute liver failure, which led the medical team to consider an evaluation for liver transplantation.

Conclusions: Acetaminophen poisoning is a frequent emergency with potentially fatal consequences. Although NAC is an effective antidote, adjustments in the duration of therapy should be individualized based on serum acetaminophen levels, individual patient response and resolution of hepatic injury, improvement coagulation and resolution of acidosis. This case supports the importance of a flexible, tailored approach to NAC administration in cases of severe acetaminophen poisoning, adapting the duration of NAC perfusion to the patient's specific needs.

#32

Detection of psychoactive substances in a tertiary hospital from 2019 to 2022: A descriptive study

I. A. Díaz Rengifo, T. Lahoz Hormigos, L. Galán Caballero, S. Mosquera Ferrer, P. P. Bermejo Martínez, N. G. Lara Gonzalez, J. C. Rodríguez Molina, A. I. Terleira Fernández and M. R. Salas Butrón

Hospital Clínico San Carlos, Madrid, Spain

Objectives: To describe the frequency in detection of psychoactive substances and demographic characteristics of consumers.

Material and/or methods: A retrospective observational study was conducted analysing the requests for abused drugs in urine and blood ethanol in the San Carlos Clinical Hospital in Madrid from 1 January 2019 to 31 December 2022. The urinary substance detection was done by enzymatic immunoassay and immunoassay for ethanol.

Results: A total of 1405 request were obtained, of which 62.7% were men and the mean age was 36.7 years (±15.7). Reasons for request were due to behavioural symptoms in 61.1% of cases, followed by 22.2% medical conditions (e.g. epilepsy) and 16.7% substance abuse. 58.5% of requests originated from the emergency department.

Positive detections occurred in 51.4% of cases; however, frequency of detection for each substance (more than one substance per request) was 41.5% were benzodiazepines, 31% ethanol, 23.4% cannabinoids, 13.6% cocaine, 5.4% amphetamines and 4.1% opiates. More than one substance was detected in 18.4% of the requests. 30.3% of detections were found in the age range of 18–29 years (mainly due to cannabinoids in 39.5%), followed by 21.6% between 40 and 49 years and 19.9% between 30 and 39 years (both mainly by benzodiazepines in 43.8% and 34.8% respectively). Notoriously, an increasing trend was found in the detection for those younger than 18 years from a 3.2% in 2019 up to a 13.5% in 2022, mainly for benzodiazepines (42.3%), followed by cannabinoids and alcohol.

Conclusions: Substance abuse continues to be a public health issue. These results shows greater consumption related to hypnotic-sedatives such as benzodiazepines detected in 41.5% of cases, followed by ethanol and cannabinoids in 31% and 23.4% respectively. When analysed by age group, the prevalence of detection is higher between 18 and 29 years with cannabinoids. Special attention is required for the under-18-year population that shows a four times increase in substance detection between 2019 and 2022.

#33

Descriptive study of drugs of abuse in psychiatric admissions to a tertiary hospital

I. A. Díaz Rengifo, T. Lahoz Hormigos, P. P. Bermejo Martínez, L. Galán Caballero, S. Mosquera Ferrer, N. G. Lara Gonzalez, J. C. Rodríguez Molina, A. I. Terleira Fernández and M. R. Salas Butrón

Hospital Clínico San Carlos, Madrid, Spain

Objectives: To describe the pattern of drug abuse among hospitalized psychiatric patients and their demographic characteristics.

Material and/or methods: Substance abuse is an important part of the psychiatric pathology. Patients with drug abuse usually have more severe symptoms and worst social outcomes. A retrospective observational study was conducted analysing the urinary drugs of abuse and blood ethanol tests requested in hospitalized psychiatric patients in a tertiary hospital. The substance detection was done by enzymatic immunoassay for urinary drugs and immunoassay for ethanol.

Results: A total of 521 request were processed from January 2019 to December 2022, of which 59.3% were men and the mean age of patients was 36.2 years (SD ± 13.4). 50.9% of requests originated from hospitalization and 48.8% from the emergency department.

Positive detections occurred in 50.5% of cases; detection for each substance was 41.2% benzodiazepines, 29.1% cannabinoids, 11.7% cocaine, 8% ethanol, 2.6% amphetamines and 2.42% opiates. More than one substance was detected in 17.5% of requests. Most detections were in the age range of 18–29 years (34.6%), mainly associated with cannabinoids (49%) in this group. Admission was involuntary in 68.3% against 31.7% voluntary. Most common diagnoses were on the psychotic spectrum (44.3%). A difference in the diagnosis and admission type was observed, with the psychotic diagnoses being more frequent during involuntary admissions (42.2% with drug detection) and non-specified behavioural symptoms during voluntary admissions (49.4% with drug detection). An increasing trend was noted with involuntary admissions from 2019 (57.2%) to 2022 (82.4%).

Conclusions: Although most of the evaluated parameters did not directly correlate to drug detection, these results show greater consumption of benzodiazepines, detected in 41.2% of cases, followed by cannabinoids and cocaine in 29.1% and 11.7%, respectively. A trend was observed in an increase in the number of involuntary admissions from 2019 to 2022.

#37

Implementing the ‘flipped classroom’ approach in clinical pharmacology education

E. J. Sanz Álvarez^1,2 and C. Rodríguez Jiménez^1,2

¹Universidad de La Laguna, La Laguna, Spain; ²Hospital Universitario de Canarias, La Laguna, Spain

Objectives: Teaching clinical pharmacology in medicine can benefit from new pedagogical approaches that increase active student participation and involvement in learning. The ‘flipped classroom’ model is a practical way to facilitate student participation in their teaching–learning process.

Material and/or methods: A flipped classroom system was implemented in the subject ‘Therapeutics and Clinical Pharmacology’ in the fifth year of the degree in medicine at the University of La Laguna. Before the classroom session, students must watch/study a video with theoretical content and embedded questions (H5P). Clinical cases and problems related to the subject during the lecture are discussed through digital systems (WOOCLAP). In addition, students must prepare a personalized vademecum according to the six steps of the WHO's ‘Guide to Good Prescribing’ through an app prepared by the teachers (https://pdrugs.ull.es).

To evaluate the effectiveness of teaching, students took the ‘European Prescribing Exam’, developed by the education committee of the EACPT (https://www.prescribingeducation.eu/) before starting teaching (on the first day of class) and as the final exam of the subject.

Results: The level of student satisfaction was very high (overall satisfaction: 8.6; usefulness of the subject: 9). The ‘European Prescribing Exam’ consists of two parts: one of knowledge and another of ‘skills’ (prescription clinical cases). A total of 101 students took both tests. In the knowledge part, the initial score (before the course) was 5.8 ± 1.3 points, and the final score (in the final exam) rose to 9.2 ± 1.0 (t-student p < 0.0001). In the ‘skills’ part, the initial score was 2.0 ± 1.6, and the final score reached 7.0 ± 2.3 (t-student p < 0.0001).

Conclusions: The ‘flipped classroom’ method in teaching clinical pharmacology is feasible, has great acceptance among students and improves scores on the European Prescribing Exam. However, it implies a much greater dedication on the part of the teaching staff.

#38

Improving clinical pharmacology teaching in Europe: A collaborative effort

E. J. Sanz Álvarez

Universidad de La Laguna, La Laguna, Spain; Hopsital Universitario de Canarias, La Laguna, Spain

Objectives: Deficiencies in prescribing practices are a concern across Europe. The EACPT Education Subcommittee has spearheaded a collaborative effort to elevate clinical pharmacology (CP) teaching standards to address this. Having been a partner in all these projects from the beginning, I know that it is relevant to spread awareness within our society.

The complete information is available at https://prescribingeducation.eu.

Results: These initiatives represent a significant step towards improved CPT education in Europe. The EuroPE+ ensures competency, EurOP2E provides a standardized resource pool, and CP4T empowers teachers to deliver high-quality instruction.

The availability of those resources is relevant for all CPT teachers in Spain.

Conclusions: The EACPT Education Committee's dedication to enhancing CP teaching deserves widespread recognition, and these initiatives merit being widely recognized by our education committee and all members of our society.

As a partner member of the EACPT education committee, I would be available to help implement these resources into CPT education in Spanish universities.

#70

Description of the publications of research studies promoted by primary care in Catalonia

A. Moleras Serra, A. Gómez Lumbreras, E. Zabaleta Del Olmo, R. Morros Pedrós and C. Vedia Urgell

IDIAPJGol, Barcelona, Spain

Objectives: To describe the scientific production (publications) of projects led and conducted in primary care (PC) in Catalonia and the relation between type of project and publication.

Material and/or methods: Observational study of the publications from studies led by PC researchers and managed by the IDIAPJGol between 2010 and 2021. Project variables: design, study topic; publication variables: yes/no, number, impact factor (IF). Categorical variables were described with absolute and relative frequencies, and continuous variables with mean and standard deviation. The confidence interval was 95%. The p-value was provided with a risk α = 0.05.

Results: A total of 1039 studies were identified, of which 62.5% (649) were observational, 23.4% (243) were experimental, 38.8% (403) the studied topic was a disease and 64.9% (674) were led by a woman.

From the total, 426 (41%) had publications. Among those with publications, the mean of publications was 1.1 (SD 2.5), and IF was 13.8 (SD 30.3). Study designs were 39.90% (249) observational studies, 33% (25) qualitative and 52.10% (38) other studies, without significant differences (p = 0.115). There were also no significant differences in the number of publications (p = 0.655) or the average of IF (p = 0.307).

The number of publications was higher in studies on medicines, 53.20% (20) compared to studies on medical devices, cosmetics or nutritional products, 44% (22) or studies primarily focused on a disease, 43.20% (174) (p < 0.001). The differences were also significant in the number of publications (p < 0.001) and the IF (p = 0.008).

In 45.5% (166) projects with publications were led by men versus 38.6% (260) by women (p = 0.018).

Conclusions: Despite the higher overall rate of observational studies, experimental studies had more publications although the differences were not significant. The study topic and the sex of the PI were significantly related factors to the percentage of publications.

#84

Retrospective study on neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in ALK-positive non-small cell lung cancer (NSCLC)

N. G. Lara Gonzalez¹, J. D. Benitez Fuentes², I. A. Diaz Rengifo¹, P. P. Bermejo Martinez¹, R. Bach Mora³, T. Lahoz Hormigos¹, C. Lacalle Gonzalez⁴, C. Martin Bravo⁵, E. Vargas-Castrillón¹ and A. F. Jimenez Ortega⁶

¹Hospital Clínico San Carlos, Madrid, Spain; ²Hospital General Universitario de Elche, Elche, Spain; ³Hospital del Mar, Barcelona, Spain; ⁴Fundación Jiménez Díaz University Hospita, Madrid, Spain; ⁵Hospital Costa del Sol, Marbella, Spain; ⁶Medical Affairs Novartis, Madrid, Spain

Objectives: To evaluate the prognostic impact of NLR on progression-free survival (PFS) and overall survival (OS) in ALK-positive NSCLC and to determine optimal NLR prognostic thresholds.

Material and/or methods: This study included patients with ALK-positive NSCLC treated with crizotinib or alectinib at four Spanish hospitals from 1 May 2011 to 31 December 2021, with follow-up until 31 May 2022. A multivariate Cox model was used to assess NLR's impact on PFS and OS, with thresholds identified via maximally selected log-rank statistics (MSLRS).

Results: A total of 54 patients met the selection criteria. The mean patient age was 61.78 years (SD: 14.93), and the median baseline NLR was 3.81 (IQR: 4.89). The majority of patients (64.8%) received crizotinib, whereas 35.2% were prescribed alectinib. After adjustments for sex, ECOG, stage, smoking status, therapy and treating hospital, each unit increase in NLR was associated with shorter PFS (HR: 1.11, 95% CI: 1.05–1.17) and OS (HR: 1.10, 95% CI: 1.04–1.16).

MSLRS identified optimal NLR thresholds of 7.7 for OS and 6.81 for PFS. NLR levels above 7.7 meaningfully increased the risk of death (HR: 10.36, 95% CI: 2.89–37.18), while levels above 6.81 were not significantly associated with shorter PFS (HR: 2.08, 95% CI: 0.93–4.69).

Conclusions: NLR may be an independent prognostic factor for survival and progression in ALK-positive NSCLC. As a readily available and inexpensive biomarker, clinicians should consider its potential integration into clinical prognostic models. Further studies with larger cohorts are warranted to confirm and implement these findings.

#87

Activity of a research ethics committee of primary care

C. Miranda Jiménez^1,2, C. Ibáñez Filella¹, C. Vedia Urgell^1,3,4, S. Fernández García^1,5,6, À. Cartanya Hueso¹, A. Moleras Serra^1,5, A. Resa Campos⁷ and R. Morros Pedrós^1,2,5

¹Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; ²UICEC de IDIAP Jordi Gol-Plataforma ScREN, Barcelona, Spain; ³Servei Atenció Primària Maresme, Barcelona, Spain; ⁴Institut Català de la Salut, Barcelona, Spain; ⁵Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain; ⁶Universitat Girona, Girona, Spain; ⁷Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola Del Vallès), Spain

Objectives: The objective of this study is to describe the activity of an Ethics Committee of Primary Care during 2023 and to analyse the type of evaluated projects, the researcher's diversity and the most frequent deficiencies.

Material and/or methods: It was a descriptive observational study during 2023 using the Ethics Committee's database. It described, through absolute frequency and percentage, the investigator's specialty, the project's design, data sources used (primary source (informed consent) or secondary source (pseudonymized electronic health records)), the projects that had used artificial intelligence and the ethics committee's decisions, analysing the type of clarifications requested.

Results: During the last year, 301 projects were evaluated. Design: 58% observational, 22% experimental and 11% qualitative. Seventeen per cent of the projects investigated drugs, 16% educational interventions, and 2% used artificial intelligence. Seventy-one per cent of the projects used an informed consent form to obtain data, and 29% used pseudonymized data, from local extractions (34%), central extractions, through SIDIAP (52%) or PADRIS (14%). Regarding the principal investigator, 47% of the cases were doctors, 27% nurses and 26% other professionals (clinical pharmacologists, psychologists, pharmacists, nutritionists, physiotherapist, odontologists or community workers). Only 51 studies received a direct approval (18%), being 238 (82%) the ones needing clarifications: data protection (89%), methodology (68%), ethical aspects (57%), logistics (12%) and others. Finally, 39% of the projects required a second request for clarifications.

Conclusions: The Ethics Committee assessed mostly observational studies, mainly conducted by medicine and nursing professionals. The percentage of studies with clarifications was very high and was mainly related to data protection, methodology and ethical aspects.

#102

Understanding the opioid crisis: The use of the Dopesick, a commercial TV series, in a clinical pharmacology course in medical students

M. Farré Albaladejo¹, C. Pérez Mañá¹, E. Montané Esteva¹, J. A. Garcia Vicente^2,3, S. Videla Ces¹ and E. Papaseit Fontanet¹

¹Clinical Pharmacology Department, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, Badalona, Spain; ²Universitat Autònoma de Barcelona, Badalona, Spain; ³Pharmacy Unit, Primary Care Directorate, Catalan Institute of Health, Badalona, Spain

Objectives: Commercial TV series and feature films are increasingly being used in teaching some aspects of medicine and health sciences. There are few publications that address the effectiveness of this approach in student learning. Dopesick is a drama miniseries explaining the opioid crisis, focusing on the development, approval, marketing, sales, prescription and consumption of Oxycontin™ (oxycodone) in United States and its consequences in public health.

Our objective was to evaluate the use of the Dopesick TV series to increase learning about the origins of opioid crisis in the United States and the role of pharmaceutical marketing, drug regulation and medical behaviour as agents facilitating the beginning of the crisis in a seminar of the clinical pharmacology course.

Material and/or methods: The study population comprised fifth-year undergraduate students of Medicine of our Hospital School of Medicine. We selected the complete first episode and 15 min of the second episode (total duration 70 min) in a special 2-h seminar in the Clinical Pharmacology program. The students watched the Dopesick episodes and discussed them afterward. To measure learning, we administered a seven-question multiple-choice test about opioids and oxycontin, before and after watching. We assessed students' satisfaction with the activity through a questionnaire. An exploratory comparative analysis was performed.

Results: A total of 126 students participated for 3 years (2022–2024). Post-intervention assessment scores were significantly higher than pre-intervention scores. The mean number of correct answers was 2.35 (ED, 1.1) on the pre-intervention assessment and 5.64 (ED, 0.95) on the post-intervention assessment. Student satisfaction with this teaching activity was high.

Conclusions: Seriemeducation can be a useful tool for teaching about the opioid crisis, including aspects of marketing strategies, government regulation of medicines, clinical pharmacology education and prescription control. Most students were highly satisfied with the activity.

#7

A descriptive study of clinical trials in the oncology department of a tertiary hospital

S. Mosquera Ferrer^1,2, M. Torrego Ellacuría^3,2, L. Galán Caballero^1,2, T. Lahoz Hormigos^1,2, I. A. Díaz Rengifo^1,2, P. P. Bermejo Martinez^1,2, N. G. Lara González^1,2, J. C. Rodríguez Molina^1,2, E. Vargas Castrillón^1,4,2 and M. D. R. Alfonso San Segundo⁵

¹Clinical Pharmacology Department, Hospital Clínico San Carlos, Madrid, Spain; ²Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain; ³Innovation Department, Hospital Clínico San Carlos, Madrid, Spain; ⁴Universidad Complutense de Madrid, Madrid, Spain; ⁵Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain

Objective: Our objective is to describe the clinical trials on cancer patients in a tertiary hospital in Spain.

Material and/or methods: A retrospective observational study was designed based on clinical trials carried out in the field of oncology at the Hospital Clínico San Carlos (HCSC) in Madrid (Spain). We selected studies conducted from 1 January 2018 to 31 June 2023 and collected the patients randomized between those dates. The study characteristics and demographic information from the patients included were described.

Results: One hundred eighty-one clinical trials met the inclusion criteria, adding a total of 726 patients, wherein 371 (51.10%) were women and 355 (48.90%) were male. The mean age was 65.13 (SD = 12.43) years. The most common country of origin was Spain, with 655 patients (90.22%), followed by Venezuela, with eight patients (1.10%), Colombia with seven patients (0.96%), Peru and Ecuador with six patients (0.83%) each and other 25 countries with the rest. Among the end-of-treatment reasons, disease progression was the most frequent, with 233 (32.09%) patients and 292 (40.22%) patients ending the study because of death. Regarding the clinical trials, 140 of the 181 (77.35%) were controlled, 133 (73.48%) were randomized, and 53 (29.28%) were double-blinded. Fifty-three (29.28%) of them used a placebo as a comparator. Most of the studies were phase III with 103 (56.91%), followed by phase II with 43 (23.76%).

The great majority of the trials, 138 (76.24%), were sponsored by the pharmaceutical industry, followed by collaborative groups with 31 (17.13%) and 12 (6.63%) trials being institutional. Breast cancer was the most common tumour with 39 (21.55%) studies and 160 (22.04%) patients.

Conclusions: The 181 clinical trials have provided valuable insights. The prevalence of industry-sponsored trials emphasizes the pharmaceutical collaboration in driving oncological research forward. These results offer an accurate assessment of the clinical trials in an oncology department and may provide helpful information for healthcare systems and future studies.

#17

Clinical effectiveness and bacteriological eradication of four short-course antibiotic regimens for lower urinary tract infections in adult women [SCOUT study]

R. Monfà Escolà^1,2,3, A. Garcia Sangenís^1,2,4, C. Miranda Jiménez^1,3, R. Morros Pedrós^1,2,3,4, B. Munné Barellas¹, S. Fernández García^1,2, A. Moragas Moreno⁵ and C. Llor^6,7,4

¹IDIAP Jordi Gol, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain; ³UICEC de IDIAP Jordi Gol-Plataforma ScREN, Barcelona, Spain; ⁴CIBER en Enfermedades Infecciosas Instituto Carlos III, Madrid, Spain; ⁵Institut Català de la Salut – CAP Jaume I, Tarragona, Spain; ⁶Institut Català de la Salut – CAP Manso, Barcelona, Spain; ⁷University of Southern Denmark, Odense, Denmark

Objective: The primary endpoint is clinical effectiveness at day 7, defined as the resolution of symptoms reported by women with uncomplicated community-acquired lower urinary tract infection (LUTI). These symptoms include dysuria, urgency, frequency and suprapubic pain, which are tracked in a diary. Additionally, bacterial eradication is assessed at days 14 and 28.

Material and/or methods: This is a pragmatic, multicentre, parallel-group, open randomized trial. Women aged 18 or older with symptoms of LUTI and a positive urine dipstick result are randomized into one of four groups: 2-day 3 g fosfomycin o.d., 3-day pivmecillinam 400 mg t.i.d, 5-day nitrofurantoin 100 mg t.i.d. or a single dose of 3 g of fosfomycin. The total sample size is 1120 patients. Follow-up visits are scheduled for days 7 (via phone call), 14 and 28 to assess patient progress. Urine samples are collected at the three on-site visits, and urine cultures are performed for further microbiological studies. Additionally, qualitative studies are being conducted to explore the experiences, needs and preferences of patients and general practitioners regarding LUTI management and how these align with the study results.

Results: Our project is being conducted in 30 primary care sites across four autonomous communities: Aragon, the Balearic Islands, Catalonia and Madrid. We are still in the recruitment phase and have enrolled over 700 patients so far, so we do not yet have specific results related to the main outcome. In the first qualitative study, 70 patients participating in the clinical trial were interviewed. Most of these patients could not recall which antibiotic they had taken.

Conclusions: The recruitment period has taken longer than initially expected. Burnout and high pressure in primary care sites, which persist after the COVID-19 pandemic, have significantly impacted study inclusion. Despite these challenges, we expect to complete recruitment with the largest possible sample by the end of 2024.

#19

Metabolic and endocrine adverse events reported in ClinicalTrials.gov In immune checkpoint inhibitors research: A critical review

R. Nogueiras Álvarez¹ and G. Prada Ramallal²

¹Basque Country Pharmacovigilance Unit, Osakidetza Basque Health Service, Galdakao-Usansolo University Hospital, Galdakao, Spain; ²Clinical University Hospital, Santiago De Compostela, Spain

Objective: Clinical trials (CTs) investigating different immune checkpoint inhibitors (ICIs) have been performed over the last years as treatment for different cancers. Despite their benefits, it must not be forgotten that ICIs are not risk-free. Metabolic and endocrine adverse events (AEs) should be monitored because of their clinical relevance on patients' health during anticancer treatment. The objective of this project was to investigate the quality of safety reports in CTs registered in ClinicalTrials.gov.

Material and/or methods: We performed a search in ClinicalTrials.gov from inception through 6 April 2024 to review the CTs in which the intervention/treatment included ICIs and there were metabolic/endocrine disorders reported as AEs. In order to perform a critical review, the registries of those CTs with available results were reviewed on a case-by-case basis. Those CTs where ICIs were not being administered in monotherapy were excluded.

Results: On the one hand, only 38.9% CTs for which the outcome measure registration included metabolic AEs had published results by the date of the search, and, of these, just four CTs (14.3%) involved ICI as monotherapy. Pembrolizumab was the most frequent drug in these studies. Metabolic AEs included, mainly, blood glucose alterations and blood electrolyte imbalance.

On the other hand, from the total number of CTs with reported endocrine disorders as AEs, 52.4% had public results. In this case, nivolumab was the most frequent drug being evaluated. For those CTs with ICIs in monotherapy, 75% reported some type of serious AEs (i.e. adrenal insufficiency, hypophysitis, thyroid dysfunction).

Conclusions: Metabolic and endocrine disorders associated with ICIs treatment have been described in different CTs. Although there are a considerable number of CTs involving ICIs in ClinicalTrials.gov (5101 on 6 April 2024), the registries with published results are scarce. Updated information from these and new CTs will provide valuable data on these ICI treatment-related AEs.

#39

Non-commercial research and its pragmatism: A pilot study of IDIBELL'S UICEC

A. Domingo-Carnice¹, D. Rodríguez¹, R. Llop¹, E. Palma¹, M. Sanllorente² and P. Hereu^1,2

¹Servicio de Farmacología Clínica, Hospital Universitari de Bellvitge, L'Hospitalet De Llobregat, Barcelona, Spain; ²Unidad de Investigación Clínica y Ensayos Clínicos (UICEC) - IDIBELL, L'Hospitalet De Llobregat, Barcelona, Spain

Objective: Non-commercial clinical trials represent 20% of the research studies in Spain. Clinical Research and Clinical Trials Units (UICEC) are necessary to support non-commercial clinical research.

The main objective of the study was to describe the characteristics and analyse the pragmatism of the independent research supported by the UICEC of the ‘Institut d'Investigació Biomèdica de Bellvitge’.

Material and/or methods: Pilot, single-centre, descriptive and retrospective study of four completed clinical trials (CT) supported from UICEC between 2020 and 2024. The main variable was pragmatism of the initial study protocol analysed with PRECIS-2 tool score (which contains nine domains scored between 1, very explanatory, and 5, very pragmatic) by the research team and the independent sponsor. Other variables collected were baseline and follow-up characteristics of the studies.

Results: The four CT were national multicentre, randomized and active treatment controlled; the investigational product were drugs (3) and a medical device (1). All of them presented substantial modifications, with a median of 3 (IQR 2.5). The PRECIS-2 score evaluated independently by the research team, and the sponsor was 4 (IQR 0.5). The independent sponsor evaluated three protocols. The most pragmatic domains were recruitment and localization (research team median [IQR] of 5 [0] and 4.5 [1]; sponsor 4.0 [0] and 4.0 [1]). Other coincident pragmatics domains were adherence (4.5 [0.5]) and organization (4.33 [0.5]). The most exploratory domains by research team were flexibility in treatment delivery and statistical analysis (2.5 [1.5] and 2.75 [3.25]) and for sponsor adherence and follow-up (2.3 [1] and 3.0 [1]).

Conclusions: The clinical trials analysed in this pilot study seems highly pragmatic, with concordance within both evaluations. It is feasible to carry out a study of these characteristics although it is necessary collaborations of researchers as much as possible.

#48

Challenges on new management requirements for non-commercial investigator-driven clinical trials to the safety events reporting within the new European clinical trial system

A. Lobo Acosta and C. Rosso Fernández

CTU-HUVR, Unidad De Soporte a la Investigación Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain

Objective: To describe the situation of a sample of Spanish hospitals (37 pertaining to the network SCReN) promoting non-commercial clinical trials with drugs in relation to the capacity to comply with European Regulation No. 536/2014 regarding the expeditious notification of cases to the EudraVigilance system.

Material and/or methods: Three main data related to the organization of safety communication were added to a survey designed by HUVR-CTU. A total of 37 clinical units pertaining to the ISCIII network SCReN (Spanish Clinical Research Network) were asked to comply related to their institution situation on regard to (1) EMA-SPOR (https://spor.ema.europa.eu/sporwi/) registration, if exits ORG number; (2) EudraVigilance registration situation; and (3) designated responsible for pharmacovigilance activities on behalf of sponsor (investigator-driven).

Results: The survey was completed from 17 April to 6 May 2024; in this period, several questions related were clarified, and some sites expressed their situation to not accomplish with the requirements. Complete response to the three questions was completed for 12/37 (31% of sites) and responded positively confirming requirements to EV communication.

Conclusions: Investigator-driven clinical proposals has become even more difficult regarding the complete organization of registries and institutional requirements related to EMA-CTIS and relationship with EV system. The example of sites pertaining to a specific research area (much lower than expected) give us an idea of the need of specific support. Maybe some adaptation to public research would have been of help for proposals of clinicians as it has become highly complicated.

#51

Safety activities in study drugs in a public hospital clinical trials unit (IBIS-CTU)

S. Jiménez Jorge, A. Lobo Acosta, E. López Barbazán, R. Fresneda Gutiérrez, N. García Carrera, M. Solla Fernández, B. Ibáñez Jiménez, R. Torrero Soulillou, L. Álvarez Rodríguez and C. Rosso Fernández

CTU-HUVR, Unidad De Soporte a la Investigación Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain

Objective: Safety surveillance is basic activity for any intervention performed in real patients, moreover if the intervention is a drug, even is a mandatory regulatory activity to be put on place among the procedures to perform a trial. The objective is to evaluate the workload and activities related with the accomplishment of safety requirements to perform for clinical trials with drug intervention in a public setting.

Material and/or methods: IBIS- CTU is the supporting unit to promote investigator-driven clinical trials in the IBIS setting (Institute accredited by ISCIII, which complies two of the biggest hospitals in Seville). As part of the supporting activities for the development of clinical studies, the specific pharmacovigilance procedures performed in the last 5 years is tabulated and analysed.

Results: Number of funded studies on which IBIS-CTU is the centralized point for safety reports, area of specialization, nationality, number of revision of the safety content in the study protocol, pharmacovigilance planning, reference safety information assessment, number of serious adverse events (SAE), number of serious and unexpected adverse events (SUSARs), number of reconciliations, number of data safety updated reports (DSUR), other sort of safety reports, number of data safety monitoring board (DSMB) organization and preparation of safety information, is analysed to propose a consideration of person/month needs for a study.

Conclusions: The number of studies funded by public calls in our setting is high, giving the necessity of a specific department of CT pharmacovigilance to accomplish with legislation in performing studies with drugs. Pharmacovigilance is a sponsor responsibility that must be delegated to specialized units when it is to be developed as an investigator-driven proposal, which normally is a management foundation to take the sponsors' ICH requirements.

#72

Double-blind randomized placebo-controlled trial of montelukast in long COVID patients with mild to moderate respiratory symptoms: E-SPERANZA project

S. Bonet Monne¹, F. Mera Cordero², B. Salvador Gonzalez^3,4, O. Cunillera Puértolas³, A. Sanllorente Melenchón^3,4, G. Alvarez Muñoz⁵, R. Magallon Botaya^6,7, R. Monfà Escolà^8,9, C. Miranda Jiménez^8,9 and R. Morros Pedrós^8,9

¹Servei d'Atenció Primària Baix Llobregat, Institut Català de la Salut, Cornellà De Llobregat, Spain; ²Director Unidad Long COVID Blue Healthcare, Madrid, Spain; ³Unitat de Suport a la Recerca (USR) Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), L'hospitalet De Llobregat, Barcelona, Spain; ⁴Direcció d'Atenció Primària de Metropolitana Sud, Institut Català de la Salut, L'Hospitalet de Llobregat, Barcelona, Spain; ⁵Unitat Funcional a l'Atenció Cronicitat Complexa Delta de Llobregat. Direcció d'Atenció Primària Metropolitana Sud. Institut Català de la Salut, L'Hospitalet De Llobregat, Barcelona, Spain; ⁶Departamento de Medicina, Universidad de Zaragoza, Zaragoza, Spain; ⁷Red de Investigación en Cronicidad, Atención Primaria y Prevención y Promoción de la Salud (RICAPPS), Zaragoza, Spain; ⁸Unitat d'Estudi del Medicament IDIAP Jordi Gol, Barcelona, Barcelona, Spain; ⁹UICEC de IDIAP Jordi Gol-Plataforma ScREN, Barcelona, Spain

Objective: To evaluate the efficacy of oral montelukast versus placebo in improving health-related quality of life in patients with long COVID and mild to moderate respiratory symptoms and to assess improvement in exercise capacity and functional status.

Material and/or methods: Phase III, double-blind randomized placebo-controlled trial, developed in primary care centres from Catalonia and Aragon from 2021 to 2023. Inclusion criteria: patients aged 18–80 years with mild to moderate dyspnoea lasting between 4 weeks and 12 months after onset of SARS-CoV-2 infection. Patients were randomized to 10 mg/day montelukast or placebo group for 4 weeks. The primary outcome was health-related quality of life measured by the COPD Assessment Test (CAT) (improvement ≥2 points from baseline) after 4 weeks of treatment. The sample size needed for the study was 284 patients.

Secondary outcomes are (a) exercise capacity and oxygen saturation (1-min sit-to-stand test) and (b) post-COVID-19 functional status scale.

This study has been approved by Clinical Research Ethics Committee of the IDIAPJGol (reference number 21/091-C). EudraCT number 2021-000605-24. ClinicalTrials.gov identifier: NCT04695704.

Results: Eighty-six patients were recruited (43 in each arm). 79.1% were women and mean age 46.5 years. An improvement on CAT scale was observed in 30 patients (46.5%) in montelukast group compared to 20 patients (69.8%) in placebo group [p 0.049]. The mean increase in the number of repetitions in the 1-min standing test was 1.51 in the montelukast group and 3.33 in the placebo group (p = 0.414). The increase in primary oxygen saturation was 1.61 and 1.38, respectively (p = 0.689). Improvement in the post-COVID-19 functional status scale was in zero patients in montelukast and four patients in placebo group.

Conclusions: Treatment with montelukast in patients with long COVID and mild–moderate dyspnoea did not improve the quality of life associated with respiratory symptoms compared to placebo. Results should be interpreted with caution due to the lack of sample size.

#76

AP-PriME: Clinical trial to evaluate the utility of prospective genotyping in reducing musculoskeletal adverse reactions in statin therapy

S. Almenara¹, M. Á. Seguido¹, A. Gómez-Fernández¹, T. Sanz², J. M. Izquierdo³, J. Novalbos¹ and F. Abad-Santos^1,4

¹Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain; ²Unidad de Investigación, Gerencia Asistencial de Atención Primaria, Servicio Madrileño de Salud, Madrid, Spain; ³Servicio de Farmacia, Gerencia Asistencial de Atención Primaria, Servicio Madrileño de Salud, Madrid, Spain; ⁴Universidad Autónoma de Madrid, Madrid, Spain

Objective: Statin treatment can produce musculoskeletal adverse reactions (MSARs), which can be severe. A significant percentage of these adverse reactions are due to genetic variability. The primary objective of this clinical trial is to evaluate the utility of pharmacogenetics (SLCO1B1, ABCG2 and CYP2C9) in reducing the incidence of MSARs in patients treated with statins.

Material and/or methods: AP-PriME is a pragmatic, low-intervention, cluster-randomized clinical trial involving primary care physicians and cardiology and internal medicine services at the Hospital de La Princesa. It will recruit patients starting statin therapy or changing doses.

After randomizing centres, prescribers in the intervention arm will receive pharmacogenetic training followed by a knowledge evaluation. Recruitment will last 12 months, with an estimated sample size of 1000 patients, 50% in each arm. In the intervention arm, a pharmacogenetic report will be prepared for each patient based on genotyping a saliva sample (SLCO1B1, ABCG2 and CYP2C9) at the recruitment visit, allowing prescribers to adjust statin therapy/doses within the first 15 days based on the report results. MSARs and other variables will be recorded during the first 6 months of follow-up. At the end of the follow-up (12–18 months), another evaluation will be conducted, and voluntary additional training will be offered to all prescribers.

Results: To date, we have prepared the documentation and initiated the trial, which has been approved by regulatory authorities via CTIS. Presentations about the study have been conducted at various health centres, resulting in the participation of 72 primary care physicians from 11 centres affiliated with Hospital de La Princesa. Recruitment will begin in June 2024. By the end of 2025, we expect to obtain statistical and pharmacoeconomic results to draw useful conclusions for daily clinical practice.

Conclusions: Studies demonstrating the utility of genotyping in routine clinical practice for the safety and efficacy of widely used drugs like statins are needed.

#79

Understanding sex-based differences by adverse events

P. Molina Perelló¹, J. Coimbra Hurtado¹, M. Puntes Rodríguez¹ and R. M. Antonijoan Arbós^1,2

¹Centre Investigació Medicament (CIM) Institut de Recerca Sant Pau, Barcelona, Spain; ²Department of Clinical Pharmacology Hospital Sant Pau, Barcelona, Spain

Objective: To describe the main characteristics of treatment emergent adverse events (TEAEs) and frequency by sex in healthy volunteers in phase I studies, performed at the Centre d'Investigació de Medicaments (CIM-IR Sant Pau) from 2015 to 2023.

Material and/or methods: TEAEs in healthy young volunteers with active treatment (placebo excluded) in studies with joint participation of men and women identified in the CIM-IR Sant Pau unit were collected. The variables evaluated were age, sex of the volunteers, frequency, severity and seriousness. A descriptive analysis was performed.

Results: In this period, 17 clinical trials (n = 459, 56% male vs. 44% female, median age 29 years old) were selected (first in human 59%, bioequivalence 41%; others 6%). A total of 262 TEAEs were reported by 165 volunteers in a proportion of 58% for women versus 42% for men. Moderate TEAEs were more frequently observed in woman, in contrast with mild TEAEs, which were commonly described in men. The most common TEAE tabulated as related to treatment (certain, likely and possible) was headache (44 women, 24 men) in both sexes. The AEs not related were mostly observed y in women (13 women, 6 men). Only one serious TEAE was observed in the study period and occurred in a female volunteer.

Conclusions: Frequency, severity and seriousness of TEAEs assessed were higher in women. Our data underscores the importance of considering sex-specific factors in the design and evaluation of clinical trials to better understand and mitigate the risks associated with drug development.

#82

Design and development of an academic advanced therapies (at) phase II multicentric clinical trial with anti-cytomegalovirus specific memory T lymphocytes

L. Lavin Alconero¹, A. Bermudez Rodriguez², J. L. Arroyo Rodriguez³, M. Sanchez Escamilla², C. Richard Espiga², O. Muñiz Pello³, D. Cuellar Gomez², I. Mazon Maraña², E. Ocio San Miguel² and M. García Saiz²

¹HUMV-IDIVAL, Santander, Spain; ²HUMV, Santander, Spain; ³Banco de sangre y tejidos de Cantabria (BSTC), Santander, Spain

Objective: Description of the design and start-up of a phase II clinical trial (CT) with AT.

Reviewing the organizational challenges of a multicentre academic trial.

Materia land/or methods: AT (anti-CMV memory T lymphocytes) have been used against cytomegalovirus (CMV) infection. We designed a CT with this product for the prevention of CMV infection in patients at high risk of reactivation after allogeneic transplantation (TP). We planned to recruit 32 patients. The CT has an NCT04056533 registration and 2019-002311-26EU project financed by ISCIII, ICI20/00033.

An investigational medicinal product dossier (IMPD) was a requisite prior to starting the CT, and clean room authorization to manufacture the product by BTBC was solicited to the AEMPS (Spanish Agency of Medicine and Health Products).

Results: The IMPD and CT authorizations were achieved within 4 months of submission to AEMPS and Ethical Committee. The cleanroom of BTBC got authorization in 7 months from AEMPS inspection.

During start-up, letermovir was authorized for CMV reactivation prophylaxis for the initial patient population (haploidentical donors); therefore, amendments to the protocol related to selection criteria were required, and the population was changed to patients with HLA identical donors. Updating the clinical aspects of the disease under study is essential to maintain the scientific validity of a CT and to ensure that participating subjects are not ethically harmed.

Due to low recruitment, the CT was switched from unicentric at HUMV to multicentric including two additional sites. Recruitment is 14 patients since March 2022; the implementation of a multicentre trial with a single manufacturing centre involves a logistical effort for the shipment of the medicinal product once it is produced and for centralizing the samples.

Conclusions: An adequate design supported by a solid and updated scientific basis is critical for an academic CT. Importance of the collaboration and networking of a multidisciplinary team to carry out highly complex projects.

#83

A pilot, randomized, three-arm, dose-finding, placebo-controlled, parallel study to evaluate the use of nabiximols (THC + CBD, Sativex®) for cannabis detoxification treatment versus treatment as usual

D. Martínez Bonifacio¹, M. Puntes Rodríguez¹, P. Molina Perelló¹, J. Coimbra Hurtado¹, J. Trujols Albet², X. Roca Tutusaus² and R. M. Antonijoan Arbós^1,3

¹Centre Investigació Medicament (CIM) Institut de Recerca Sant Pau, Barcelona, Spain; ²Department of Psychiatry, Hospital Sant Pau, Barcelona, Spain; ³Department of Clinical Pharmacology, Hospital Sant Pau, Barcelona, Spain

Objective: The aim of this study was to evaluate the effect of nabiximols (THC + CBD, Sativex®) in reducing withdrawal symptoms among detoxifying cannabis-dependent patients at two different doses versus treatment as usual.

Material and/or methods: Sixteen cannabis-dependent individuals seeking inpatient detoxification took part in this parallel, randomized, single-blind and placebo-controlled clinical study. Subjects received nabiximols (THC + CBD, Sativex®) low dose + usual treatment; nabiximols high dose + usual treatment; or placebo + usual treatment, during 9 days. Withdrawal symptoms and craving were assessed using The Cannabis Withdrawal Scale (CWS) and Cannabis Craving Visual Analogue Scale (VAS-CC), respectively. CWS was measured at baseline and on days 1–9 after treatment. The primary endpoint was mean withdrawal symptoms and craving versus baseline in each group. Blood was analysed to assess CBD, THC and OH-THC plasma levels at baseline, +26 h and +228 h.

Results: In CWS test, the reduction of the value was greater on the high dose (−1.09) than low dose (−0.86) and placebo (−0.54) by comparing the mean results of the test with baseline. In VAS-CC test, the high dose showed an improvement of the results compared to both low dose and placebo, with values about −52.5, −13.77 and −24.55 respectively. Regarding pharmacokinetic data, a correlation was observed between plasma levels and the reduction in scores on the two tests. These results were inversely proportional; as one increased, the other decreased.

Conclusions: Nabiximols can reduce withdrawal symptoms and craving in cannabis-dependent patients undergoing detoxification. Specifically, higher doses of nabiximols resulted in greater reductions in withdrawal symptoms compared to lower doses and placebo. The high-dose group exhibited the most significant improvements, indicating a dose–response relationship consistent with the plasma results obtained.

#89

Experimental binge drinking: Gender differences in alcohol concentrations and effects

M. Farré Albaladejo, C. Pérez Mañá, O. Hladun Alvaro, G. De La Rosa Loppacher, D. A. Caicedo, M. C. Argote Oramas, M. M. Anleu De León, S. Martin Sánchez, L. Poyatos Blanco and E. Papaseit Fontanet

Clinical Pharmacology Department, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, Badalona, Spain

Objective: Binge drinking (BD) is a well-established pattern of drinking among adolescents/young adults with an intention to becoming intoxicated. It refers to heavy alcohol use over a short period of time (2 h) that typically occurs after four standard drinks (40 g) for women and five standard drinks (50 g) for men leading to a blood alcohol concentration (BAC) of 0.8 g/L equivalent to breath alcohol concentration (BrAC) of 0.4 mg/L. In previous studies, we demonstrate similar binge drinking episodes after alcohol administration during 80 and 120 min.

The objective was to evaluate gender differences on concentration and effects of alcohol after administration simulating a BD episode along 45 min.

Material and/or methods: The study was randomized, cross-over, double bind and placebo controlled. We included 24 volunteers. Women received an oral dose of 55 g of alcohol or placebo (n = 10) and men 70 g of alcohol or placebo (n = 14) during 45 min (five glasses, total volume of 700 ml). Study variables included vital signs, subjective effects [Visual Analogue Scales (VAS)] and BrAC measured along a 10-h period.

Results: The administration produced a BD episode in both genders. Doses of alcohol showed a similar concentration (BraCA Cmax 0.62 mg/L) and acute alcohol effects in both sexes (drunkenness), but higher negative effects in women than in men.

Conclusions: Women need less dose of alcohol to achieve similar blood concentrations of alcohol but show less tolerability to alcohol when administered in a BD pattern, being more vulnerable to alcohol's effects than males.

Grants: Supported in part by Grants from Ministerio de Sanidad (Plan Nacional sobre Drogas) grant 2022I045 and Instituto de Salud Carlos III under grants PT20/00018; and RD21/0009/0004. Spain.

#114

Safety and efficacy of intracavernosal platelet-rich plasma (Prp) versus control (platelet-poor plasma) in erectile dysfunction: A randomized double-blind control trial

G. A. Centeno Soto¹, E. Fernández², J. I. Martinez Salamanca¹, J. Porcel Maleno¹, J. L. Bueno¹ and C. Avendaño Solá¹

¹Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain; ²Hospital Universitario La Paz, Madrid, Spain

Objective: To evaluate the efficacy of intracavernous injection of PRP in the treatment of vascular ED in comparison to control measured by the improved in the IIEF-EF after 28 weeks.

Material and/or methods: Men with moderate or severe vasculogenic ED who are non-responders (NR) to PDE5i were randomized to receive 6-weekly intracavernosal injections of PRP vs control. Primary outcome was the difference in improvement in the IIEF-EF from basal assessment (V3) to the assessment at 4 weeks after the end of the treatment (V9). NR were defined as <5 points improvement of the IIEF-EF at V9. NR in control arm were offered to enter into a second trial phase to receive his stored PRP.

Results: Because the recruitment period was prolonged, the percentage of NR was >70% and the appearance of fibrous plaques on the penis in three subjects, the sponsor decided to performed a futility analysis and to convene the DSMB. Although the threshold for stopping the trial for futility reasons was not reached, the conditional power was 0.36. DSMB concluded that doubts arise regarding the benefit/risk of the PRP. For these reasons, the sponsor decided to stop the trial.

Twenty-seven subjects were randomized (PRP: 13; control: 14); 26 subjects completed the main efficacy assessment. Mean changes of IIEF-EF 4 weeks after the end of the treatment for PRP were −1.25 (95% CI [−3.15–0.65]) versus 1.57 (95% CI [−0.59–3.73]) to control.

Conclusions: The results of our clinical trial show that six weekly doses of intracavernosal PRP in men with moderate to severe ED are not more effective than control, and there are relevant safety findings with the appearance of fibrous plaques in the tunica albuginea, likely related to the treatment. An extended follow-up of the trial patients is foreseen. Our results suggest there is a negative benefit–risk ratio for PRP injection in ED.