Case report: Medical cannabis—warfarin drug-drug interaction

Aim A case of an 85-year-old patient with concurrent use of warfarin and medical cannabis containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is described. Warfarin continues to be a cornerstone of anticoagulation treatment despite the recent addition of FDA-approved anticoagulant agents. It is well known that warfarin has numerous drug interactions; however, much remains unknown about its interaction with THC and CBD. A literature review was conducted to identify documented cases of possible interactions between cannabis and warfarin. The case reports we identified noted that cannabis may potentially increase warfarin’s effect. Therefore, we aimed to determine why an effect was not seen on our patient’s warfarin dose despite daily use of medical cannabis. Case This case report describes an 85-year-old patient who despite starting an oromucosal medical cannabis regimen of THC and CBD (which provided 0.3 mg of THC and 5.3 mg CBD once daily and an additional 0.625 mg of THC and 0.625 mg CBD once daily as needed) had minimal INR fluctuations from October 2018 to September 2019. Conclusion Despite the introduction and use of medical cannabis therapy, with both THC and CBD components, an elderly patient with concurrent warfarin use did not see major INR fluctuations, in contrast to published literature. The potential for warfarin and THC/CBD interactions may be dependent on route of administration and dose of the cannabis product.

Evaluation of Anticoagulation Control among Patients Taking Warfarin in University of Gondar Hospital, Northwest Ethiopia

Introduction. Warfarin is a widely used oral anticoagulant in clinical practice. It has variable intraindividual and interindividual dose response and a narrow therapeutic index. Therefore, it requires frequent and regular international normalized ratio (INR) determination to maintain the INR within the therapeutic range. The study evaluated parameters of anticoagulation control among patients on warfarin. Methods. A cross-sectional study was conducted at University of Gondar hospital. A consecutive sampling method was used to recruit study subjects. The anticoagulation control was evaluated by determining the proportion of desired INRs and the proportion of time spent in the therapeutic range (TTR). Logistic regression analysis was used to identify associated factors with adequate TTR. A P value <0.05 was used to declare significant association. Result. A total of 338 study subjects were included in the study. The mean age of patients was 48.8 (SD = 16.4) years. Atrial fibrillation was the commonest indication for warfarin therapy. One-third (33%) of study subjects achieved the desired INRs of 2.0–3.0, while about one-tenth (13%) of patients attained good INR control (TTR ≥ 65%). Multivariate logistic regression analysis revealed no significant association of sociodemographic and clinical characteristics with good TTR outcome. Conclusion. The level of anticoagulation control with warfarin among study subjects was very low. The authors recommend to implement a validated warfarin-dose titration protocol and to establish anticoagulation clinics to mitigate the low anticoagulation level.

Associated Factors and Safety of the Rapidly Achieving First Therapeutic Target of Warfarin in hospitalized Patients: A Retrospective Cohort Study

Background Warfarin is a commonly used anticoagulant drug in clinical practice. Rapidly achieving the first therapeutic international normalized ratio (INR) of warfarin may reduce the hospital length of stay. However, little research has been carried out to evaluate the influencing factors and the safety of rapidly achieving the first therapeutic INR target of warfarin. Aim To investigate the associated factors and the safety of rapidly achieving the first therapeutic INR target of warfarin. Method A retrospective cohort study was conducted in inpatients who took warfarin from November 2018 to October 2019. Patients’ information was retrieved from medical records. Results 487 patients were included. The mean achieving first therapeutic target time was 6.0 ± 3.2 days (median, 5.0 days). Age > 65 years, body mass index < 24 kg/m2, and initial warfarin dose ≥ 3 mg/d were independent factors associated with the rapidly achieving first INR target of warfarin therapy. The incidence of INR ≥ 4 was higher in patients achieving the first INR target rapidly than those achieving the first INR target slowly, while there were no significant differences in bleeding events between the two groups. Conclusion Hospitalized patients aged > 65 years, with a body mass index < 24 kg/m2, or receiving an initial warfarin dose ≥ 3mg/d were more likely to achieve the first INR target of warfarin rapidly. Closer INR monitoring and appropriate warfarin dose adjustment are recommended to improve the safety for patients achieving the first INR ≥ 1.8 within 6 days after beginning oral warfarin.

A Multicentre Study on Average Warfarin Dose to Maintain Therapeutic International Normalised Ratio with Time in Therapeutic Range of More than 75% in Atrial Fibrillation Patients

Large interindividual variability and over-anticoagulation resulting bleeding complications due to narrow therapeutic index of warfarin has causes its pharmacodynamic activity to be highly variable. Studies shown that ethnicity, age and gender contribute to warfarin response variability. Good coagulation control of time in therapeutic range (TTR) > 75% was chosen to determine the average warfarin dose in atrial fibrillation (AF) among ethnicity, age and gender. Data from Warfarin Medication Therapy Adherence Clinic of selected Pulau Pinang hospitals were used for the analysis of average warfarin dose in AF among ethnicity, age and gender. Patients who fulfilled the inclusion criteria from 2015–2016 were followed up for a year. Five hundred and seventy-six patients were included. Two hundred and ten patients had good coagulation control of TTR > 75% with mean warfarin dose of 3.05 ± 1.25 mg. Only Chinese and Indian have significant difference in average warfarin dose with 2.86 ± 1.10 mg and 4.11 ± 1.40 mg, respectively (p = 0.008). Average warfarin dose was found not significantly different among gender and age. As for TTR achievement, 210 (36.4%) were able to achieve TTR > 75%, 134 patients achieved TTR 60%–75% and 232 patients has TTR < 60%. The median day to achieve three consecutive targeted international normalised ratio (INR) is 186.5 days for atrial fibrillation patient newly started on warfarin therapy in 2015 until 2016. Indian patients required a higher warfarin dose than Chinese patients. This study found that mean warfarin doses were not affected by age and sex.

Machine Learning for Prediction of Stable Warfarin Dose in US Latinos and Latin Americans

Populations used to create warfarin dose prediction algorithms largely lacked participants reporting Hispanic or Latino ethnicity. While previous research suggests nonlinear modeling improves warfarin dose prediction, this research has mainly focused on populations with primarily European ancestry. We compare the accuracy of stable warfarin dose prediction using linear and nonlinear machine learning models in a large cohort enriched for US Latinos and Latin Americans (ULLA). Each model was tested using the same variables as published by the International Warfarin Pharmacogenetics Consortium (IWPC) and using an expanded set of variables including ethnicity and warfarin indication. We utilized a multiple linear regression model and three nonlinear regression models: Bayesian Additive Regression Trees, Multivariate Adaptive Regression Splines, and Support Vector Regression. We compared each model’s ability to predict stable warfarin dose within 20% of actual stable dose, confirming trained models in a 30% testing dataset with 100 rounds of resampling. In all patients (n = 7,030), inclusion of additional predictor variables led to a small but significant improvement in prediction of dose relative to the IWPC algorithm (47.8 versus 46.7% in IWPC, p = 1.43 × 10−15). Nonlinear models using IWPC variables did not significantly improve prediction of dose over the linear IWPC algorithm. In ULLA patients alone (n = 1,734), IWPC performed similarly to all other linear and nonlinear pharmacogenetic algorithms. Our results reinforce the validity of IWPC in a large, ethnically diverse population and suggest that additional variables that capture warfarin dose variability may improve warfarin dose prediction algorithms.