Warfarin–rifampin interaction has been reported since the 1970s. Due to rifampin’s strong induction of CYP2C9, most cases could not attain the target international normalized ratio (INR) despite warfarin dose escalation. Genetic polymorphisms determine up to 50% of warfarin dose variability. A 38-year-old woman was started on warfarin and rifampin for cerebral venous sinus thrombosis and pulmonary tuberculosis. Over six weeks, the daily warfarin dose was increased from 3 to 10 mg to attain three consecutive in-clinic therapeutic INRs. She completed three complications-free months of warfarin treatment with time in therapeutic range (TTR) of 46%. We performed retrospective genetic testing to determine the patient’s CYP2C9, CYP4F2, and VKORC1 genotypes and whether they had affected the interaction outcome. The analysis revealed that the subject carries CYP2C9*3*3 and VKORC1-1639 (GA) mutations, classifying her as a slow metabolizer and, hence, highly warfarin-sensitive. This was reflected on how the case responded to a relatively lower dose than previously reported cases that did not achieve the target on warfarin daily doses up to 35 mg. This is the first report addressing the genotype effect on this interaction. Patients with genetic variants requiring low warfarin doses are more likely to respond at a feasible dose while on rifampin. Future studies to evaluate warfarin–rifampin-gene interaction are warranted.

Warfarin is extensively metabolized by cytochrome P450 2C9 (CYP2C9). Concomitant use with the potent CYP2C9 inducer, rifampin, requires close monitoring and dosage adjustments. Although, in theory, warfarin dose increase should overcome this interaction, most reported cases over the last 50 years have not responded even to high warfarin doses, but some have responded to modest doses. To investigate the genetic polymorphisms' impact on this unexplained interpatient variability, we performed genotyping of CYP2C9, VKORC1, and CYP4F2 for warfarin and rifampin concomitant receivers from 2016 to 2022 at Hamad Medical Corporation, Doha, Qatar. We identified and included 36 patients: 22 responders and 14 nonresponders. Warfarin‐responders were significantly more likely to have one or more warfarin‐sensitizing CYP2C9/VKORC1 alleles than nonresponders (odds ratio = 23.2, 95% confidence interval = 3.2–195.6; P = 0.0001). The mean genetic‐based pre‐interaction calculated dose was significantly lower for responders than for nonresponders (P < 0.001); and was negatively correlated with warfarin sensitivity index (WSI) (r = −0.58; P = 0.0002). The median percentage time in therapeutic range and mean WSI were significantly higher in the warfarin‐sensitizing CYP2C9/VKORC1 alleles carriers than noncarriers (P = 0.017 and 0.0004, respectively). Whereas the warfarin‐sensitizing CYP2C9/VKORC1 genotypes were associated with modest on‐rifampin warfarin dose requirements, the noncarriers would have required more than double these doses to respond. Warfarin‐sensitizing CYP2C9/VKORC1 genotypes and low genetic‐based warfarin calculated doses were associated with higher warfarin sensitivity and better anticoagulation quality in patients receiving rifampin concomitantly.

Achieving vancomycin therapeutic levels is essential for antibacterial success and resistance prevention. Multiple studies have shown that most of the children fail to reach therapeutic trough levels (10–20 µg/mL). This study aims to determine the frequency of achieving therapeutic vancomycin initial trough levels in children, evaluate the effect of age on that achievement and the mean initial trough levels, and the frequency of supratherapeutic levels. Children aged 1 month to 12 years who received three or more vancomycin doses 15 mg/kg every 6 h while admitted at our hospital from February 2016 to January 2017, and had a level before the fourth dose were included. Cases with high baseline serum creatinine, acute kidney injury, and congenital heart disease were excluded. Out of 75 included cases, one third, 28/75 (37.3%), achieved goal. The lowest frequency was 6/28 (21.4%) of the 2–5 years group, which were statistically less likely to achieve, and had significantly lower mean initial trough than the 1–23 months group (P = 0.026 and 0.013, respectively). Mean initial trough levels were 10.1, 7.3, and 8.2 µg/mL in the 1–23 months, 2–5 years, and 6–12 years groups, respectively (P = 0.014). No supratherapeutic levels were observed. Vancomycin dose of 60 mg/kg/day is insufficient to attain target levels for most of the children. Children aged 2–5 years are the least likely to achieve and have the lowest mean levels. More intensified doses are warranted to be studied prospectively to identify the most effective empiric dose for children.

Lamotrigine has been repeatedly reported to cause hematologic toxicities, which may be associated with high initial doses or excessive escalation. A 29‐year‐old lady experienced profound neutropenia after two weeks of lamotrigine high initial dose, started within two days of phenytoin. The too‐early dose intensification may have produced lamotrigine‐induced blood dyscrasia.

Introduction: Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m²). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. Methods: We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. Results: Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17–1.92), (OR 1.55, 95% CI 1.29–1.86), (OR 2.92, 95% CI 1.87–4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93–1.52). Discussion: In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m²) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

Introduction: Despite recent advances in clinical therapeutics in patients with venous thromboembolism, uncertainty remains regarding the optimal anticoagulation strategy in patients with intermediate‐ to high‐risk pulmonary embolism. We aimed to evaluate the direct oral anticoagulants’ effectiveness and safety compared to warfarin in patients with intermediate‐ and high‐risk pulmonary embolism.Methods: In this meta‐analysis, we systematically searched databases PubMed, EMBASE, Web of Science, and the Cochrane Library from their inception to April 30, 2024, for eligible studies that satisfy inclusion criteria. We included both randomized clinical trials and observational studies reporting on patients diagnosed with intermediate‐risk or high‐risk pulmonary embolism who were prescribed warfarin or direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban). Two independent reviewers extracted relevant data from included studies based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guideline. Pooled odds ratios were derived from the included studies using the random‐effects model. The primary outcomes were the rate of venous thromboembolism recurrence and all‐cause mortality. Secondary outcomes were major and minor bleeding.Results: Six studies, five observational and one randomized (n = 553 patients, out of which 45.7% received advanced therapy), were included in our meta‐analysis. Direct oral anticoagulants were associated with comparable recurrence and mortality rates versus warfarin (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.15–3.43) and (OR 0.57, 95% CI 0.16–2.01), respectively. There was no significant difference in the safety outcomes (major and minor bleeding events), with a trend towards a decreased risk among direct oral anticoagulant treated cohorts (OR 0.3, 95% CI 0.08–1.1) and (OR 0.64, 95% CI 0.24–1.7), respectively.Conclusion: In patients with intermediate‐ to high‐risk pulmonary embolism, with or without advanced therapy use, stabilized on direct oral anticoagulants, efficacy and safety outcomes were comparable to those on warfarin, with a trend towards less risk of major and minor bleeding events.Trial registration: International PROSPERO database number: CRD42024499532