Annals of Pharmacotherapy最新文献

{"title":"Apixaban Dose Selection in Kidney Failure: Reconciling Pharmacokinetics and Clinical Outcomes.","authors":"Soon H Yang","doi":"10.1177/10600280261479334","DOIUrl":"https://doi.org/10.1177/10600280261479334","url":null,"abstract":"<p><strong>Objective: </strong>To compare pharmacokinetic, clinical outcomes, and regulatory evidence for apixaban 5 mg versus 2.5 mg twice daily in kidney failure on hemodialysis with atrial fibrillation (AF), and propose a framework for individualized dose selection.</p><p><strong>Data sources: </strong>PubMed, EMBASE, and the Cochrane Library were searched from inception through June 2026 using terms including apixaban, kidney failure, hemodialysis, AF, pharmacokinetics (PK), and dosing.</p><p><strong>Study selection and data extraction: </strong>PK studies, observational cohorts, randomized controlled trials (RCTs), network meta-analyses, regulatory documents, and guidelines evaluating apixaban dosing in kidney failure and AF were included.</p><p><strong>Data synthesis: </strong>Five PK studies (n ≈ 112) showed 2.5 mg twice daily produced steady-state levels comparable to 5 mg in normal renal function, while 5 mg produced approximately 3-fold supratherapeutic exposure. Of the 3 observational studies, 2 linked 5 mg to lower mortality; 1 found 63% higher bleeding with 5 mg and no difference in stroke/systemic embolism (subdistribution hazard ratio (SHR) 1.01; 95% CI, 0.59-1.73) or death (hazard ratio [HR] 1.03; 95% CI, 0.77-1.38). Two RCTs (RENAL-AF and AXADIA-AFNET 8) were terminated early and remain underpowered. Confounding by indication, competing risk of death, and misapplication of dose-reduction criteria likely explain this paradox.</p><p><strong>Relevance to patient care and clinical practice: </strong>This review provides the first systematic reconciliation of this paradox, identifying confounding by indication, competing risk of death, and structural flaws in the US Food and Drug Administration (FDA) dose-reduction criteria as likely explanations for the discordance. It gives clinical pharmacists a framework for appraising the evidence rather than defaulting to the FDA label or PK data alone, and proposes a decision algorithm for individualized dosing, derived from expert opinion, PK, and observational data and requiring prospective validation.</p><p><strong>Conclusions: </strong>The optimal apixaban dose in kidney failure remains unresolved. Neither dose has been shown to reduce stroke versus no anticoagulation in this population. Dose selection should be individualized to patient-specific factors.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261479334"},"PeriodicalIF":2.5,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Vonoprazan-Tetracycline Dual Therapy Versus Bismuth-Containing Quadruple Therapy for <i>Helicobacter pylori</i> Eradication: A Systematic Review and Meta-analysis.","authors":"Amna Amir Jalal, Syeda Samia Fatima, Abdul Wasio, Rohma Zubairi, Sundus Malik, Rutaba Darooj, Sameer Mehmood, Baneen Javed Arain, Ayesha Ashar, Ayesha Arif, Syed Ibad Hussain","doi":"10.1177/10600280261478500","DOIUrl":"https://doi.org/10.1177/10600280261478500","url":null,"abstract":"<p><strong>Objective: </strong>To compare the efficacy and safety of 14-day vonoprazan-tetracycline (VT) dual therapy versus bismuth-containing quadruple therapy (BQT) for <i>Helicobacter pylori</i> eradication.</p><p><strong>Data sources: </strong>PubMed/MEDLINE, Scopus, Cochrane Library, and Google Scholar were systematically searched from database inception through July 1, 2026, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms included combinations of \"<i>Helicobacter pylori</i>,\" \"vonoprazan,\" \"tetracycline,\" \"dual therapy,\" \"bismuth quadruple therapy,\" \"eradication,\" and \"randomized controlled trial (RCT).\"</p><p><strong>Study selection and data extraction: </strong>Eligible studies were RCTs comparing 14-day VT dual therapy with BQT in adults with confirmed <i>H pylori</i> infection. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Random-effects meta-analyses were performed using pooled risk ratios (RRs) with 95% confidence intervals (CIs), and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.</p><p><strong>Data synthesis: </strong>Three RCTs involving 1050 participants were included. Vonoprazan-tetracycline dual therapy achieved eradication rates comparable to BQT in intention-to-treat (RR = 1.00, 95% CI, 0.93-1.07), per-protocol (RR = 0.97, 95% CI, 0.93-1.01), and modified intention-to-treat analyses (RR = 1.01, 95% CI, 0.97-1.06). Vonoprazan-tetracycline significantly reduced total adverse events (TAEs) (RR = 0.31, 95% CI, 0.21-0.45), treatment discontinuation due to adverse events (RR = 0.12, 95% CI, 0.02-0.87), nausea (RR = 0.17, 95% CI, 0.08-0.35), and diarrhea (RR = 0.22, 95% CI, 0.08-0.67). The GRADE assessment demonstrated moderate-certainty evidence for efficacy outcomes and high-certainty evidence for most safety outcomes.</p><p><strong>Relevance to patient care and clinical practice: </strong>Vonoprazan-tetracycline dual therapy offers a simplified, penicillin-sparing regimen with eradication efficacy comparable to BQT and substantially improved tolerability. These findings support VT as a clinically relevant alternative for patients in whom treatment adherence, adverse effects, or penicillin avoidance are important considerations.</p><p><strong>Conclusions: </strong>Vonoprazan-tetracycline dual therapy provides eradication efficacy comparable to BQT while offering a significantly improved safety profile. Larger multinational RCTs are needed to confirm these findings and further define its role in first-line <i>H pylori</i> eradication.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261478500"},"PeriodicalIF":2.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Duration of Intravenous Octreotide Infusion on Achieving Hemostasis in Patients With Acute Variceal Hemorrhage.","authors":"Tien Q Pham, Jason R Yerke, Michael A Rudoni, Christina C Lindenmeyer, Aanchal Kapoor, Stephanie N Bass","doi":"10.1177/10600280261478164","DOIUrl":"https://doi.org/10.1177/10600280261478164","url":null,"abstract":"<p><strong>Background: </strong>In acute variceal hemorrhage (AVH), guidelines recommend 2 to 5 days of octreotide following endoscopic hemostasis to reduce early rebleeding; however, the optimal duration of therapy remains undefined.</p><p><strong>Objective: </strong>To evaluate whether a shorter duration of octreotide therapy is non-inferior to a longer duration in preventing early rebleeding and adverse clinical outcomes.</p><p><strong>Methods: </strong>This multicenter, retrospective non-inferiority study included adults with cirrhosis and endoscopically confirmed AVH admitted to 13 hospitals within the Cleveland Clinic Health System between January 2020 and August 2024. Patients were categorized by post-endoscopic octreotide infusion duration: short-course (≤72 h) or long-course (>72 h). The primary outcome was 5-day rebleeding, with a prespecified non-inferiority margin of 15%. Secondary outcomes included 48-hour rebleeding, transfusion requirements, in-hospital mortality, adverse events, and octreotide-related costs.</p><p><strong>Results: </strong>Among 260 patients, 131 received short-course and 129 received long-course octreotide therapy. Rebleeding within 5 days occurred in 27.5% and 31.0% of patients, respectively (absolute risk difference = -3.5%; 95% confidence interval = -14.6% to 7.5%), meeting the non-inferiority threshold. Secondary outcomes were similar: 48-hour rebleeding (17.6% vs 20.2%), median blood transfusion (0 vs 0 units), and in-hospital mortality (10.7% vs 18.6%). Rates of bradycardia, hypo- or hyperglycemia, and ileus did not differ. Octreotide-related treatment costs were significantly lower in the short-course group.</p><p><strong>Conclusion and relevance: </strong>In patients with AVH who achieved endoscopic hemostasis, short-course octreotide therapy was non-inferior to longer-course therapy in preventing early rebleeding, with similar clinical outcomes and lower treatment cost.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261478164"},"PeriodicalIF":2.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relacorilant in Combination With Nab-Paclitaxel for the Treatment of Adults With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.","authors":"Emilie J Lynch, Lauren T Carpenter, Kelli N Corona, Adebola O Fatimilehin, Nathan D Seligson","doi":"10.1177/10600280261477395","DOIUrl":"https://doi.org/10.1177/10600280261477395","url":null,"abstract":"<p><strong>Objective: </strong>To review the pharmacology, efficacy, and safety of relacorilant (Lifyorli) in combination with nab-paclitaxel (NP) for the treatment of adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 3 prior lines of systemic therapy, including at least one bevacizumab-containing regimen.</p><p><strong>Data sources: </strong>A literature search was conducted using Embase and PubMed/MEDLINE, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and July 1, 2026. Keywords included relacorilant, Lifyorli, and CORT125134.</p><p><strong>Study selection and data extraction: </strong>All English-language studies involving relacorilant for the treatment of cancer or other conditions were included.</p><p><strong>Data synthesis: </strong>Relacorilant is a highly selective, nonsteroidal, reversible glucocorticoid receptor antagonist approved in combination with NP based primarily on a phase 3 clinical trial of 381 patients, in which relacorilant plus NP significantly improved progression-free and overall survival compared with NP alone. Serious adverse events (AEs) occurred in 35% of patients receiving the combination, although treatment discontinuation due to AEs was uncommon. Common AEs associated with the combination included neutropenia, anemia, thrombocytopenia, nausea, and fatigue.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Platinum-resistant ovarian cancer remains a difficult-to-treat disease with limited therapeutic options. Unlike biomarker-restricted therapies, relacorilant plus NP improved survival outcomes in a heavily pretreated, biomarker-independent population.</p><p><strong>Conclusion: </strong>Relacorilant represents a novel strategy for reversing chemoresistance in combination with NP alongside a manageable safety profile for heavily pretreated patients with platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancers.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261477395"},"PeriodicalIF":2.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Early Heparin Response in Patients With Venous Thromboembolism.","authors":"Ronith Murali, Stephanie B Edwin, Lillian Martin, Maureen Smythe, Christopher Giuliano","doi":"10.1177/10600280261477748","DOIUrl":"https://doi.org/10.1177/10600280261477748","url":null,"abstract":"<p><strong>Background: </strong>Unfractionated heparin (UFH) is widely used for treatment of acute venous thromboembolism (VTE); however, its anticoagulant response is highly variable. Delays in achieving therapeutic anticoagulation have been associated with increased mortality, suggesting a potential role for predictive modeling to guide dosing.</p><p><strong>Objective: </strong>To develop predictive models to estimate probability of therapeutic or supratherapeutic level attainment at the time of first activated partial thromboplastin time (aPTT) and the UFH infusion rate at the time of first therapeutic aPTT.</p><p><strong>Methods: </strong>This retrospective, cohort study included hospitalized patients with a new diagnosis of VTE receiving protocolized UFH (80 units/kg bolus followed by 18 units/kg/h infusion). Patients were excluded for protocol deviations, anticoagulation reversal, hypothermia, or pregnancy. The primary outcome was development of a predictive model for attainment of therapeutic or supratherapeutic aPTT at first follow-up. A secondary model was developed that predicted heparin infusion rate at the time of first therapeutic aPTT. Multivariable logistic and linear regression models were developed with variable selection using least absolute shrinkage and selection operator. Model performance was assessed using discrimination and calibration.</p><p><strong>Results: </strong>Among 398 included patients, 83.2% achieved a therapeutic or supratherapeutic aPTT at initial follow-up. Eleven predictors were included in the primary model (age, sex, race, white blood cell count, creatinine clearance, body mass index, total bilirubin, albumin, platelets, propofol exposure, and coagulopathy) and demonstrated moderate discrimination (area under the curve [AUC] = 0.744) with acceptable calibration for predicting UFH response. Prediction of heparin dose at initial therapeutic aPTT incorporated a subset of these variables along with additional predictors (weight, Glasgow Coma Scale, baseline aPTT, active viral infection, and aspartate aminotransferase) and demonstrated substantial performance (<i>R</i>² = .714).</p><p><strong>Conclusion and relevance: </strong>Clinical and laboratory factors influence UFH response and dosing requirements. These models may support individualized dosing strategies to improve time to therapeutic anticoagulation, although external validation is needed before clinical application.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261477748"},"PeriodicalIF":2.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Hematologic Reserve and Laboratory-Defined Leukopenia/Neutropenia During Vancomycin Therapy: A Real-World Risk-Stratification Cohort Study.","authors":"Dong Wu, Xiaowu Wang, Changjing Chen, Xiaoying Wang, Hao Li, Linlin Zhao, Guangli Li, Xiaojuan Wang","doi":"10.1177/10600280261476308","DOIUrl":"https://doi.org/10.1177/10600280261476308","url":null,"abstract":"<p><strong>Background: </strong>Laboratory-defined leukopenia/neutropenia may occur during vancomycin therapy, but mild threshold-crossing abnormalities do not necessarily establish definite drug-induced toxicity.</p><p><strong>Objective: </strong>To develop and evaluate a risk-stratification strategy based on baseline hematologic reserve and vancomycin treatment duration.</p><p><strong>Methods: </strong>This single-center retrospective cohort included adult inpatients receiving intravenous vancomycin for ≥3 days. Patients with baseline leukopenia/neutropenia, hematologic disease, malignancy or antitumor therapy, non-intravenous use, or unavailable blood counts were excluded. The primary endpoint was laboratory-defined leukopenia/neutropenia, defined as new white blood cell count (WBC) <4.0 × 10⁹/L or absolute neutrophil count (ANC) <2.0 × 10⁹/L during therapy or within 3 days after discontinuation. A 4-component baseline hematologic reserve score was constructed from WBC, ANC, monocyte count, and hemoglobin.</p><p><strong>Results: </strong>Among 506 patients, 75 developed leukopenia/neutropenia, corresponding to an event rate of 14.8%. The score assigned 1 point each for WBC ≤7.77 × 10⁹/L, ANC ≤6.62 × 10⁹/L, monocyte count ≤0.40 × 10⁹/L, and hemoglobin ≤102 g/L. Event rates increased from 7.5% to 40.9% across scores of 0 to 4 (<i>P</i> for trend < .001), and were 8.6%, 12.2%, and 34.5% in the low-, intermediate-, and high-risk groups, respectively. Compared with the low-risk group, the score-defined high-risk group had higher odds of laboratory-defined leukopenia/neutropenia (adjusted odds ratio [OR] 7.52, 95% CI, 3.95-14.33, <i>P</i> < .001). Vancomycin duration >14 days was also independently associated with the outcome (adjusted OR 5.08, 95% CI, 2.77-9.29, <i>P</i> < .001). The highest risk was observed in high-risk patients treated for >14 days, with an event rate of 75.0%. The baseline score model showed moderate performance (area under the curve [AUC] 0.697), whereas the extended model incorporating the score-defined risk group, treatment duration, and clinical covariates improved discrimination (AUC 0.786).</p><p><strong>Conclusion and relevance: </strong>A 4-component baseline hematologic reserve score combined with treatment duration may help identify patients who warrant closer complete blood count monitoring during vancomycin therapy. These findings should be interpreted as laboratory-event risk stratification rather than proof of definite vancomycin-induced toxicity or as a mandatory discontinuation threshold.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261476308"},"PeriodicalIF":2.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologic Strategies for Anemia in Patient Blood Management: A Systematic Review and Practical Clinical Synthesis.","authors":"Antonio Alceu Dos Santos, Carlos Eduardo Panfilio, Alana Jocelina Montenegro de Castro, Selma Soriano, Nelson Americo Hossne Junior, Regiane Chiavelli Lamim, Julia Ayumi Monobe, Maria Stella Figueiredo, Isabel Cristina Céspedes","doi":"10.1177/10600280261471906","DOIUrl":"https://doi.org/10.1177/10600280261471906","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to provide a practical clinical summary for the effective management of anemia using vitamin B12, folic acid, and especially iron combined with erythropoietin (EPO), to facilitate the implementation of the Patient Blood Management (PBM) program in hospitals.</p><p><strong>Data sources: </strong>The review followed the PRISMA 2020 statement, and the protocol was registered in PROSPERO. A systematic literature search was conducted in the Cochrane Library, PubMed, PubMed Central, MEDLINE, EMBASE, EBSCO, and LILACS.</p><p><strong>Study selection and data extraction: </strong>Randomized controlled and observational studies were included, while selected reviews were used for contextual interpretation. Data were synthesized qualitatively within a practical clinical synthesis framework, and certainty of evidence was assessed using the GRADE approach.</p><p><strong>Data synthesis: </strong>A total of 2495 records were identified, 156 articles underwent full-text review, and 43 studies were included. Across studies, therapy with vitamin B12, folic acid, and iron, as well as EPO, was associated with increased hemoglobin levels and reduced allogeneic transfusion requirements. Reported iron regimens included oral elemental iron at 60 to 120 mg/day and intravenous iron at 10 to 20 mg/kg/week, with maximum weekly doses ranging from 600 to 1000 mg, depending on formulation. Reported EPO regimens included 600 IU/kg/week administered intravenously or subcutaneously for moderate-to-severe anemia and 300 IU/kg/day in critical settings. Heterogeneity was observed in dosing strategies, timing, and routes of administration across studies.</p><p><strong>Relevance to patient care and clinical practice: </strong>This review provides an evidence-informed clinical framework to support physicians, pharmacists, and nurses in the pharmacologic management of anemia. Synthesizing commonly reported strategies for intravenous iron and erythropoietin therapy facilitates the implementation of the first pillar of PBM and supports clinical decision-making.</p><p><strong>Conclusions: </strong>Iron and erythropoietin therapy were consistently associated with increased hemoglobin levels and reduced allogeneic transfusion requirements. The dosing regimens identified across studies provide a practical evidence-informed framework for anemia management within PBM programs.Systematic Review Protocol:CRD420261295920 (PROSPERO).</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261471906"},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Levetiracetam Versus Sodium Valproate in Pediatric Epilepsy: A Systematic Review and Meta-analysis.","authors":"Zahabia Adnan, Amna Amir Jalal, Abdullah Hameed, Syed Hassan Ali, Shanza Shakir, Syed Ibad Hussain, Eisha Abid, Ahmed Asad Raza","doi":"10.1177/10600280261471544","DOIUrl":"https://doi.org/10.1177/10600280261471544","url":null,"abstract":"<p><strong>Objective: </strong>To compare the efficacy and safety of levetiracetam versus sodium valproate as antiseizure therapy in children with new-onset epilepsy or established status epilepticus.</p><p><strong>Data sources: </strong>PubMed, Cochrane Library, Embase, and Scopus were searched from inception to March 2026, without language restriction, using combinations of \"epilepsy,\" \"status epilepticus,\" \"pediatric,\" \"levetiracetam,\" and \"sodium valproate,\" with hand-searching of reference lists.</p><p><strong>Study selection and data extraction: </strong>Randomized controlled trials and cohort studies of levetiracetam versus sodium valproate in children (≤18 years) were eligible. Two reviewers independently screened records, extracted data, and appraised quality (Cochrane RoB 2; Newcastle-Ottawa Scale for the cohort study). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects Mantel-Haenszel model, with certainty graded by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.</p><p><strong>Data synthesis: </strong>Eight studies (7 randomized trials and 1 prospective cohort) were included. Levetiracetam and sodium valproate were comparably effective for seizure freedom (RR = 1.01; 95% CI = 0.93-1.10) and for failure to achieve seizure freedom (RR = 1.00; 95% CI = 0.73-1.36). Levetiracetam significantly reduced overall AEs (RR = 0.78; 95% CI = 0.68-0.89) and weight gain (RR = 0.22; 95% CI = 0.10-0.46), both high certainty. Behavioral changes (RR = 2.15; 95% CI = 0.81-5.70) and skin rash (RR = 1.01; 95% CI = 0.50-2.04) did not differ significantly.</p><p><strong>Relevance to patient care and clinical practice: </strong>This is among the first meta-analyses to pool pediatric data for these agents across both new-onset epilepsy and status epilepticus and to grade outcome certainty. The findings support levetiracetam as a preferred initial monotherapy when weight, tolerability, reproductive safety, or interaction risk is a priority, with behavioral monitoring during use.</p><p><strong>Conclusions: </strong>Levetiracetam and sodium valproate offer similar seizure control in pediatric epilepsy and status epilepticus, but levetiracetam has a more favorable safety profile, particularly for adverse effects and weight gain. High-quality pediatric trials with longer follow-up are needed to confirm the long-term efficacy.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261471544"},"PeriodicalIF":2.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doravirine/Islatravir: A 2-Drug Regimen for the Treatment of HIV-1 Infection.","authors":"Elias B Chahine, David E Koren, Rafik Samuel, Harrison Van der Kloot, Elizabeth M Sherman","doi":"10.1177/10600280261472079","DOIUrl":"https://doi.org/10.1177/10600280261472079","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to review the efficacy and safety of doravirine/islatravir for the treatment of HIV-1 infection.</p><p><strong>Data sources: </strong>A literature search was conducted in PubMed and Google Scholar (January 2016-June 2026) using the search terms <i>doravirine</i> or <i>MK-1439</i> and <i>islatravir</i> or <i>MK-8591</i>. Other resources included abstracts presented at recent conferences and the prescribing information.</p><p><strong>Study selection and data extraction: </strong>All English-language studies assessing the efficacy and safety of doravirine/islatravir for the treatment of HIV-1 infection were included.</p><p><strong>Data synthesis: </strong>Doravirine is an established second-generation nonnucleoside reverse transcriptase inhibitor. Islatravir is a new nucleoside reverse transcriptase inhibitor that uniquely interferes with translocation and is highly active against HIV-1. Doravirine/islatravir once daily was shown to be safe and effective in three phase 3 clinical trials, using a lower dose of islatravir (0.25 mg), after a higher dose (0.75 mg) was shown in earlier trials to reduce total lymphocyte and CD4+ T-cell counts. The FDA approved this combination for the treatment of HIV-1 infection in adults who are virologically suppressed on stable antiretroviral therapy with no history of virologic treatment failure and no known resistance to doravirine.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Doravirine/islatravir is the first integrase strand transfer inhibitor-free 2-drug regimen indicated for the treatment of HIV-1 infection. The combination could be useful for patients who want to simplify their regimen and those who cannot receive an integrase inhibitor.</p><p><strong>Conclusions: </strong>Doravirine/islatravir is safe and effective as a 2-drug regimen for the treatment of HIV-1 infection.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261472079"},"PeriodicalIF":2.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obecabtagene Autoleucel in Relapsed/Refractory B-ALL: A Critical Review of Clinical Efficacy and Safety.","authors":"Emily Hu, Sarah Johnson, Timber Abinsay, Michael Angelo Confiado, Grace Cobb, Kelli Corona, Lauren Carpenter, Jessica Huston","doi":"10.1177/10600280261470829","DOIUrl":"https://doi.org/10.1177/10600280261470829","url":null,"abstract":"<p><strong>Objective: </strong>This article reviews the published data encompassing the development, pharmacology, efficacy, and safety of obecabtagene autoleucel, summarizing data from pivotal clinical studies and clinical relevance in the treatment of relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL).</p><p><strong>Data sources: </strong>A literature review was conducted in PubMed and Clinicaltrials.gov from inception through May 2026, using terms \"AUCATZYL®,\" \"obecabtagene autoleucel,\" \"obe-cel,\" \"AUTO1,\" and \"CAR-T cell therapy.\"</p><p><strong>Study selection and data extraction: </strong>Clinical data and studies were limited to those published in the English language which discussed the safety and efficacy of obecabtagene autoleucel.</p><p><strong>Data synthesis: </strong>Obecabtagene autoleucel (obe-cel) is an autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy using a novel CAT19 single-chain variable fragment designed with an intermediate affinity and fast binding off-rate mechanism. In the pivotal FELIX study, an overall remission rate of 77% was achieved in the primary adult cohort (IIa), with a median event-free survival rate of 11.9 months across all cohorts. Safety data indicate a manageable toxicity profile, and economic models suggest significant cost savings regarding adverse event management.Relevance to Patient Care and Clinical Practice in Comparison to Existing Agents:Obe-cel provides a new treatment option for adults with R/R B-ALL, a population that historically faces poor prognosis and high recurrence rates.</p><p><strong>Conclusion: </strong>While logistical complexities and high acquisition costs remain an access barrier to CAR-T cell therapies, obe-cel's molecular design and safety profile represent a significant advancement in the care of patients with R/R B-ALL.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":" ","pages":"10600280261470829"},"PeriodicalIF":2.5,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}