Pharmacotherapy最新文献

{"title":"Incretin-Based Therapies for the Treatment of Binge Eating-A Systematic Review.","authors":"Raechel T White, Penelope Henriquez, Britnee Innocent, Krystal Bullers, Amre Elmaoued","doi":"10.1002/phar.70135","DOIUrl":"10.1002/phar.70135","url":null,"abstract":"<p><strong>Introduction: </strong>Binge eating disorder (BED) is a common psychiatric condition associated with psychological and cardiometabolic morbidity. Psychotherapy remains a core treatment modality while pharmacologic agents such as lisdexamfetamine, selective-serotonin reuptake inhibitors (SSRIs), and topiramate demonstrate variable efficacy and tolerability. Incretin therapies-specifically glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA-originally developed for type 2 diabetes mellitus (T2DM) and obesity, are an emerging therapy of interest for BED due to their effects on satiety, appetite regulation, and reward-driven eating. This systematic review examines current data surrounding the efficacy of incretin therapies in treating BED and discusses potential mechanisms underlying their effects.</p><p><strong>Methods: </strong>This systematic review was registered with PROSPERO (CRD42024615851) and conducted in accordance with PRISMA 2020 guidelines. Comprehensive searches were performed across MEDLINE, Embase, PsycINFO, Scopus, and Cochrane CENTRAL from inception to December 2024. Eligible studies included human trials evaluating GLP-1 RAs or dual GLP-1/GIP agonists in patients with diagnosed BED or binge eating behaviors. Data were extracted on study design, interventions, eating disorder outcomes, psychiatric symptoms, weight, and cardiometabolic measures.</p><p><strong>Results: </strong>Of 1125 screened records, 12 studies met inclusion criteria. Interventions studied included liraglutide, semaglutide, and dulaglutide, with sample sizes generally < 75 participants. Despite heterogeneity in study design and outcome measures, consistent reductions in binge eating behaviors were observed, reflected by improvements in Binge Eating Scale scores, reductions in binge frequency, and remission rates. GLP-1 RAs were also associated with significant reductions in body weight (-3 to -24 kg), BMI, and improvements in glycemic control among individuals with diabetes. Adverse effects were primarily gastrointestinal, with no new psychiatric safety concerns identified.</p><p><strong>Discussion: </strong>GLP-1 RAs may offer dual therapeutic benefits for BED, reducing binge eating behaviors while addressing comorbid obesity and metabolic consequences. However, available evidence is limited by small sample sizes, heterogeneous methods, and short follow-up durations. Larger randomized controlled trials using standardized diagnostic criteria and validated psychiatric measures are warranted.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70135"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Monotherapy: The Superior Efficacy of Combined GLP-1 Receptor Agonist and SGLT2 Inhibitors on Renal Biomarkers: A Systematic Review and Meta-Analysis.","authors":"Aya M AbdelMagid, Ahmed M Kamel, Samar F Farid","doi":"10.1002/phar.70142","DOIUrl":"10.1002/phar.70142","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a leading cause of chronic and end-stage renal diseases. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer renoprotection; however, emerging evidence suggests that combination therapy has synergistic benefits. This meta-analysis evaluated dual versus monotherapy, focusing on the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. PubMed, Scopus, Embase, CINAHL, Medline, and Web of Science were searched until August 2025 for RCTs comparing GLP-1RA plus SGLT2i versus monotherapy or placebo in adults with T2D. The primary outcome was the change in UACR, and the secondary outcome was eGFR. Pooled standardized mean differences (SMD) were estimated using random-effects models, including subgroup and sensitivity analyses. Eight RCTs (n = 1974; sample size, 41-4000; follow-up, 16 weeks-3.4 years) were included. Combination therapy was well tolerated and significantly reduced UACR compared with monotherapy (SMD -0.25, 95% confidence interval (CI) -0.38, -0.13; I² = 0%). The benefits remained significant against SGLT2i alone (SMD, -0.28) but not for GLP-1RA alone. For eGFR, dual therapy provided a modest benefit versus SGLT2i (SMD 0.12, 95% CI 0.00-0.23) but not for GLP-1RA. The effects were consistent in patients with DKD and in larger trials. Early SGLT2is and GLP-1RA combination therapy is safe and provides superior renoprotection compared to monotherapy in patients with type 2 diabetes, albuminuria, and high cardiorenal risk. Broader adoption of combination therapy could improve outcomes, although cost and access barriers remain an issue.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70142"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Cardiovascular Outcomes of GLP-1 Receptor Agonists in Women With Type 2 Diabetes and Breast Cancer.","authors":"Cyrille K Cornelio, Kevin Cowart, Janelle Perkins, Mohammed E Alomar, Ricardo Pineda Gayoso, Aimon C Miranda, Anh T Phan, Raechel T White","doi":"10.1002/phar.70130","DOIUrl":"10.1002/phar.70130","url":null,"abstract":"<p><strong>Introduction: </strong>The cardiovascular (CV) benefits of glucagon-like-peptide-1 receptor agonist (GLP-1 RA) therapies are not well-established in women with breast cancer and type 2 diabetes (T2D).</p><p><strong>Objectives: </strong>The primary objective of this study was to compare the incidence of major adverse cardiovascular events (MACE) in women with T2D and breast cancer receiving GLP-1 RA therapy versus non-GLP-1 RA diabetes medications.</p><p><strong>Methods: </strong>This retrospective study included women with T2D, diagnosed with breast cancer at ≥ 40 years old from December 16, 2014 to December 16, 2024 and having exposure to diabetes medications of interest (either GLP-1 RA or non-GLP-1 RA) within 5 years of these diagnoses. The primary end point, MACE, was a composite of myocardial infarction, ischemic stroke, coronary revascularization, cardiac arrest, or heart failure, within 5 years of the index date. Propensity score matching was performed. Participants were excluded from each individual outcome analysis if they had the outcome prior to the index date. Incidence rates, risk ratio (RR), 95% confidence interval (CI), and p-value were reported for each outcome.</p><p><strong>Results: </strong>After matching, 19,608 patients were included in each cohort (mean age 64 years). Obesity and alkylating agents were more commonly reported in the GLP-1 RA cohort. Semaglutide was the most prescribed GLP-1 RA at index (45.1%). MACE occurred in 10.6% of the GLP-1 RA cohort and 13.4% of the non-GLP-1 cohort (RR 0.80, 95% CI 0.75-0.85, p < 0.001). Individual MACE end points, ischemic heart disease, and end-stage renal disease were significantly lower in the GLP-1 RA-treated cohort. GLP-1 RA use was also associated with a 61.6% relative risk reduction in all-cause mortality (RR 0.38, 95% CI 0.36-0.41, p < 0.001). Pancreatitis incidence was similar between groups (p = 0.057), whereas cholelithiasis was significantly lower with GLP-1 RA therapy (p < 0.001).</p><p><strong>Conclusions: </strong>This study demonstrated the potential CV benefit of GLP-1 RA therapies among a population of female breast cancer survivors with T2D. Randomized trial data are needed to confirm these findings.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70130"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Losartan in Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer: A Randomized, Controlled Study.","authors":"Aalaa Mahmoud Ahmed Shawqi Mahmoud, Emad Shash, Hayam Ateyya, Farida A Okasha, Nouran Omar El Said","doi":"10.1002/phar.70124","DOIUrl":"10.1002/phar.70124","url":null,"abstract":"<p><strong>Background: </strong>Paclitaxel-induced peripheral neuropathy (PIPN) is a condition that persists chronically in more than 60% of affected individuals, and currently there are no proven PIPN prophylaxis. Pre-clinical data suggest the angiotensin-II-receptor blocker losartan may attenuate neuro-inflammation and nerve injury. This study was conducted to assess losartan's neuroprotective effect against PIPN in patients with breast cancer.</p><p><strong>Methods: </strong>In this single-center, open-label, randomized, controlled trial, women with early-stage breast cancer scheduled for weekly paclitaxel (80 mg/mg² or 12 doses) were enrolled and randomized 1:1 to losartan 100 mg once daily plus standard care or standard care alone. The primary end point was incidence of grade 2 or higher neuropathy, per National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE v5.0). Secondary end points included time-to-neuropathy (in days), patient quality of life (QoL) assessed by Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX), pain intensity using visual-analogue scale (VAS), serum nerve growth factor (NGF) levels, and safety.</p><p><strong>Results: </strong>Between December 2023 and December 2024, 89 Patients Were Randomized (Losartan, n = 45; Control, n = 44). Losartan Significantly Reduced Grade ≥ 2 Neuropathy Incidence (33.3% vs. 86.4%, p < 0.001) and Delayed Its Onset (73.27 vs. 43.75 Days; Hazards Ratio [HR] = 0.2, 95% Confidence Interval [CI]: 0.11-0.35) Compared With Standard Care Alone, Respectively. At 12 Weeks, Patients Treated With Losartan Reported Superior QoL (FACT/GOG-NTX: 31.87 ± 6.43 vs. 15.45 ± 10.04; p < 0.001) and Reduced Pain Scores (Median VAS 3 vs. 8; p < 0.001) Compared With Standard Care Alone, Respectively. NGF Levels Were Comparable and Adverse Events Were Similar Between Groups.</p><p><strong>Conclusions: </strong>Daily losartan reduced and delayed clinically significant paclitaxel-induced neuropathy while improving patient-reported outcomes, without additional toxicity. These findings support repurposing losartan as a low-cost PIPN prophylactic and justify validation in larger, multicenter trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT06135493).</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70124"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DILIConsult: A Multi-Agent Large Language Model Framework for Evaluating Drug-Induced Liver Injury in ICU Settings.","authors":"Alfred Zheng Ting Ho, Jeren Zheng Feng Law, Aiwen Wang, Daniel Yan Zheng Lim, Jasmine Chiat Ling Ong","doi":"10.1002/phar.70131","DOIUrl":"10.1002/phar.70131","url":null,"abstract":"<p><strong>Background: </strong>Large language models (LLMs) can support clinical decision-making by parsing databases and extracting relevant information. However, evaluating drug-induced liver injury (DILI) often requires processing lengthy clinical histories alongside reference materials like LiverTox, which can exceed context lengths of conventional LLMs. Challenges such as information truncation hinder standard approaches like prompt engineering and retrieval-augmented generation (RAG). To address these limitations, this study introduces DILIConsult, an agentic LLM pipeline based on GPT-4, designed to intelligently parse clinical and drug information.</p><p><strong>Methods: </strong>To develop DILIConsult, we compared GPT-4-Turbo versus GPT-4o for extracting DILI characteristics from LiverTox descriptions. We tested two approaches to analyzing cases of suspected DILI: full-length case analysis versus sequential drug-specific evaluations. We evaluated DILIConsult on cases of suspected DILI identified from the open source Medical Information Mart for Intensive Care-IV (MIMIC-IV) ICU dataset based on American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) criteria. Outputs from DILIConsult were compared against a panel of clinicians comprising an ICU pharmacist, an ICU junior attending physician, and an ICU resident. Responses were evaluated by two senior ICU attending physicians.</p><p><strong>Results: </strong>Using GPT-4o and a sequential approach demonstrated improved performance in the extraction of DILI characteristics and analysis of suspected DILI. DILIConsult achieved the best mean rank of 1.66 ± 0.75 in knowledge recall and ranked second for reasoning (2.00 ± 0.64) and reflection of current medical consensus (2.05 ± 0.62). DILIConsult ranked last with mean ranks of 2.07 ± 0.52 and 2.09 ± 0.72 for less omission of important information and content inaccuracy, respectively.</p><p><strong>Conclusion: </strong>DILIConsult demonstrates the potential of LLMs to assist clinicians in evaluating DILI. The findings emphasize the importance of task division in LLM-driven workflows to minimize information loss.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70131"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Recaticimab in Dyslipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Mohammed R Abdeldayem, Ahmed Elsherbeeny","doi":"10.1002/phar.70129","DOIUrl":"10.1002/phar.70129","url":null,"abstract":"<p><p>Dyslipidemia is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). Recaticimab is a novel humanized monoclonal antibody that specifically targets proprotein convertase subtilisin/kexin type 9 (PCSK9). It has shown promising results in reducing low-density lipoprotein cholesterol (LDL-C) levels. Here, we aim to further investigate the safety and efficacy of recaticimab in patients with dyslipidemia. We comprehensively searched PubMed, Scopus, Web of Science, and Cochrane Library databases to identify all randomized controlled trials (RCTs) comparing recaticimab with placebo. Eligible RCTs were selected, and their data were extracted and analyzed using the RevMan software. Four studies involving 1657 patients were included in this meta-analysis. In terms of efficacy outcomes, compared with the placebo group, recaticimab significantly decreased levels of LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), triglyceride (TG), and lipoprotein(a) [Lp(a)], with the following values, respectively: (mean difference (MD): -52.62, 95% confidence interval (CI) [-57.25, -47.99], p < 0.00001); (MD: -47.03, 95% CI [-48.96, -45.11], p < 0.00001); (MD: -44.33, 95% CI [-46.08, -42.58], p < 0.00001); (MD: -8.83, 95% CI [-13.03, -4.63], p < 0.0001); and (MD: -29.21, 95% CI [-32.10, -26.31], p < 0.00001). In terms of safety outcomes, there was no significant difference between recaticimab and placebo groups in the incidence of any adverse events (odds ratio (OR): 1.16, 95% CI [0.90, 1.51], p = 0.26), serious adverse events, upper respiratory tract infections, or elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT). However, recaticimab was associated with higher odds of injection site reactions compared with placebo (OR: 2.65, 95% CI [1.24, 5.67], p = 0.01). Recaticimab significantly reduced LDL-C levels and was associated with a manageable safety profile, even with dosing intervals of up to 12 weeks. Further studies should be conducted globally in larger and more diverse patient populations.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70129"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Glucagon-Like Peptide-1 Receptor Agonists on Proteinuria in Kidney Transplant Recipients.","authors":"Stephanie Shabanowitz, Ryan Clark, Rachel Bassett Allen, Mary Chandran, Anita Yang","doi":"10.1002/phar.70123","DOIUrl":"10.1002/phar.70123","url":null,"abstract":"<p><strong>Introduction: </strong>Proteinuria is a marker of kidney dysfunction and increased cardiovascular mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown significant cardiorenal benefits in chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). However, the impact of GLP-1 RAs on cardiorenal outcomes in kidney transplant recipients (KTRs) remains unclear. This study aims to assess the effect of GLP-1 RA therapy on proteinuria and metabolic parameters in KTRs, with and without T2DM, 12 months following GLP-1 RA initiation.</p><p><strong>Methods: </strong>A single-center, retrospective study was conducted to evaluate the safety and efficacy of GLP-1 RAs in adult KTRs from June 1, 2022 to December 31, 2023. Primary outcomes were changes in urine protein-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) at 1, 3, 6, and 12 months after initiation of GLP-1 RAs. Secondary outcomes assessed changes in estimated glomerular filtration (eGFR), body mass index (BMI), and hemoglobin A1c (A1C). Safety outcomes included cardiovascular hospitalizations, acute kidney injury, pancreatitis, and biopsy-proven rejection within 12 months.</p><p><strong>Results: </strong>Forty KTRs received GLP-1 RA therapy with a mean time to initiation of 4.3 months post-transplant, and the majority of patients had T2DM (87.5%). Baseline UPCR and UACR were 0.86 and 669 mg/g, respectively. UPCR at 1, 3, and 6 months post-initiation was 0.38 g/g, 0.37 g/g, and 0.30 g/g, respectively. UACR at 1, 3, and 6 months post-initiation was 313 mg/g, 285 mg/g, and 234 mg/g, respectively. A 55% decrease from baseline in UPCR and UACR was observed at 1 month (p = 0.070) and a 50% decrease from baseline was observed at 12 months (p = 0.058), achieving UPCR of 0.43 g/g and UACR of 320 mg/g. A1C, eGFR, and BMI remained stable. Minimal safety events occurred.</p><p><strong>Conclusion: </strong>GLP-1 RAs demonstrated clinically significant improvements in proteinuria as early as 1 month post-initiation in KTRs. Proteinuria significantly improved from severely increased to moderately increased at 6 months following GLP-1 RAs, with good tolerability. GLP-1 RAs may offer renal benefits in KTRs with T2DM without compromising allograft function. Future studies should include closer monitoring of KTRs on immunosuppression with high gastrointestinal adverse effect profiles, and larger studies are needed to assess the long-term impact of GLP-1 RAs in KTRs irrespective of T2DM.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70123"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Stimulant Treatment in Preventing Fractures and Head Injuries in Patients With Narcolepsy: A Self-Controlled Case Series Study.","authors":"Yunlong Zheng, Toshiki Fukasawa, Soichiro Masuda, Masato Takeuchi, Takayuki Anno, Koji Kawakami","doi":"10.1002/phar.70132","DOIUrl":"10.1002/phar.70132","url":null,"abstract":"<p><strong>Background: </strong>Previous cohort studies have investigated whether stimulants reduce injury risk in narcolepsy, but they faced potential biases such as confounding by indication and immortal time bias. We conducted a self-controlled case series study to address these biases and assess the effect of stimulant use on the risk of fracture and head injury in patients with narcolepsy.</p><p><strong>Methods: </strong>We used a Japanese health insurance claims database to identify patients with narcolepsy who were newly exposed to stimulants and who experienced fracture or head injury. We then applied multivariable conditional Poisson regression models to estimate adjusted incidence rate ratios (aIRRs) and their 95% confidence intervals (CIs) for outcomes, comparing the focal window with the referent window. Subgroup analyses assessed individual stimulants (methylphenidate, modafinil, and pemoline).</p><p><strong>Results: </strong>Among 1790 new stimulant users, 233 had fracture and 189 had head injury. Overall stimulant use was not associated with fracture (aIRR, 0.89; 95% CI, 0.57-1.39) or head injury (aIRR, 1.40; 95% CI, 0.87-2.25). In subgroup analyses, methylphenidate use was associated with a lower fracture risk (aIRR, 0.28; 95% CI, 0.08-0.94) but did not affect head injury (aIRR, 1.16; 95% CI, 0.34-3.92). We observed no association between modafinil or pemoline and either outcome.</p><p><strong>Conclusion: </strong>Our results indicate that overall stimulant use did not decrease the risk of fracture or head injury in patients with narcolepsy. However, methylphenidate may help prevent fractures. Clinicians should balance the safety and effectiveness of each stimulant with additional preventive strategies for injury.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70132"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of Clinically Significant Drug-Drug Interactions With Phenobarbital and Primidone.","authors":"Kyrellos Ghattas, Ji Tong Liu, Pansy Elsamadisi, Anna Morien-Medoff, Adrian Wong","doi":"10.1002/phar.70133","DOIUrl":"10.1002/phar.70133","url":null,"abstract":"<p><p>Phenobarbital (PB) is historically used for management of seizure disorders but more recently has emerged as a prominent option for the management of alcohol withdrawal syndrome given data suggesting its benefit over benzodiazepines. An important consideration of PB therapy is its induction of cytochrome-P 450 enzymes (CYP450), which may lead to underrecognized drug-drug interactions (DDIs). Knowledge of these PB DDIs, including their onset and offset, is important to better elucidate how to manage these DDIs. To identify published literature evaluating the relevance of DDIs between PB and selected medications, a systematic review was performed including literature published through January 2026, focused on the administration of both PB and a list of medications based on tertiary medication database review as well as clinical relevance, including anticoagulants, antimicrobials, and immunosuppressants. Included articles had to identify outcomes of interest, which were focused on laboratory, pharmacokinetic, and clinical outcomes, and had to be in humans. Data extraction included the onset and offset of PB DDIs and potential PB dose-response and magnitude of induction of target medication. A total of 3271 articles were identified, with 50 studies meeting inclusion criteria, which included both adult and pediatric populations. Thirteen studies evaluated onset of PB induction, which ranged from 6 h to 30 days. Eight studies evaluated offset of PB induction, which ranged from 2 to 8 weeks. Limited data demonstrated a PB dose-response relationship in terms of magnitude of CYP induction. We found that 86% of the included studies demonstrated an impact by PB on outcomes, which were often related to therapeutic drug monitoring. Data suggest that PB does lead to clinically significant DDIs in multiple classes of medications. Future areas of research include focused evaluations on clinical outcomes, as well as studies specifically evaluating single high-dose PB and impact on DDI outcomes.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70133"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current State of Clinical Care of People With Cystic Fibrosis.","authors":"Cameron J McKinzie, Charissa W Kam, Paul M Beringer, Brittany A Wright, Wendy M Bullington, Sabrina Garcia, Jonathan J Grant, Rebecca S Pettit, David C Young","doi":"10.1002/phar.70138","DOIUrl":"10.1002/phar.70138","url":null,"abstract":"<p><p>The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has dramatically changed the landscape of the clinical care of people with cystic fibrosis (PwCF). In particular, highly effective modulator therapy (HEMT) availability for the majority of PwCF has led to changes in pharmacotherapy regimens and clinical outcomes but has also been associated with adverse effects and drug interactions. The role of CFTR modulator therapy perinatally continues to be of great interest, related to both the mother with CF as well as the infant in utero and after birth. As the median life expectancy for PwCF continues to increase, consideration must also be given for treatment of cardiovascular disease and other comorbidities as well as cancer screening and other preventative care measures.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 4","pages":"e70138"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}