Drug Interaction Between Favipiravir and Warfarin: A Case Series.

Introduction: Initiating favipiravir in COVID-19 patients with long-term warfarin use can lead to increased INR. However, data on the onset and duration of the increasing INR are limited. Method: We reviewed patient charts to include COVID-19 adult patients who received favipiravir for at least 5 days and used warfarin at the same dose for at least 12 weeks. Data on demographics, comorbidities, other medical characteristics, international normalized ratio (INR), and signs of bleeding were collected. Result: Eight patients, with a mean age of 70.88 ± 8.49 years old, received the standard dose of favipiravir. The mean maximum INR (4.30 ± 1.26) was statistically different from the baseline INR (P = .00029) and the change was observed within 4.38 ± 1.99 days after initiating favipiravir. Warfarin was then discontinued without favipiravir discontinuation in most patients, allowing the INR to gradually decrease within 2 to 3 days. Conclusion: Concurrent use of favipiravir and warfarin led to INR prolongation within approximately 4 days. The effect of such interaction can be acute as the prolongation occurred within 1 day in 1 of the patients.

Development and validation of a bleeding risk prediction score for patients with mitral valve stenosis and atrial fibrillation or mechanical heart valves receiving long-term warfarin therapy.

AIMS: This study aimed to develop and validate a new bleeding risk score to predict warfarin-associated major bleeding for patients with mitral valve stenosis with atrial fibrillation (MSAF) or mechanical heart valves (MHV). METHODS: A multicentre, retrospective cohort study was conducted at 3 hospitals in Thailand. Adult patients with MSAF or MHV receiving warfarin for ≥3 months during 2011-2015 were identified. Data collection and case validation were performed electronically and manually. Potential variables were screened using the least absolute shrinkage and selection operator. Multivariate logistic regression analysis using stepwise backward selection was used to construct a risk score. Predictive discrimination of the score was evaluated using the C-statistic. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: There were 1287 patients (3903.41 patient-year of follow-up), with 192 experiencing bleeding (4.92 event/100 patient-year) in the derivation cohort. A new bleeding risk score termed, the HEARTS-60 + 3 score (hypertension/history of bleeding; external factors, e.g., alcohol/drugs [aspirin or nonsteroidal anti-inflammatory drugs]; anaemia/hypoalbuminaemia; renal/hepatic insufficiency; time in therapeutic range of <60%; stroke; age ≥60 y; target international normalized ratio of 3.0 [2.5-3.5]), was developed and showed good predictive performance (C-statistic [95% confidence interval] of 0.88 [0.85-0.91]). In the external validation cohort of 832 patients (2018.45 patient-year with a bleeding rate of 4.31 event/100 patient-year), the HEARTS-60 + 3 score showed a good predictive performance with a C-statistic (95% confidence interval) of 0.84 (0.81-0.89). CONCLUSION: The HEARTS-60 + 3 score shows a potential as a bleeding risk prediction score in MSAF or MHV patients.

QTc prolongation in patients with COVID-19: a retrospective chart review.

Drug-induced corrected QT (QTc) prolongation can cause Torsade de Pointes (TdP) which leads to severe arrhythmia or sudden cardiac death. However, information on the prevalence of QTc prolongation in coronavirus disease 2019 (COVID-19) patients and risk factors is limited. A retrospective chart review was conducted in COVID-19 patients admitted to Chonburi Hospital from April to October 2020. The outcomes were the incidence of QTc prolongation and prevalence of risk factor QTc prolongation. We included 29 COVID-19 patients. After treatments were initiated, QTc prolongation occurred in 17 patients (58.62%). QT prolongation could be found as early as two days after the treatment initiation (median = 6 days interquartile range [IQR], 4-7). The median QTc interval in those 17 patients increased from 410 (IQR, 399.5-425.0) ms to 460 (453.50-466.50) ms, with the maximum QTc interval of 488 ms. They were treated with multiple drugs that were reported as a cause of QTc prolongation. 64.71% (n = 11) of them were treated with chloroquine. The median TdP risk score in patients with and without QTc prolongation was 3 (IQR, 2-3) and 2 (IQR, 1-2), respectively. The percentage of patients with comorbidities including atrial fibrillation, bradycardia, concomitant use of diuretics, diabetes, electrolyte imbalance was higher in patients with QTc prolongation. COVID-19 patients were treated with multiple drugs that were reported as a cause of QTc prolongation. COVID-19 patients with QTc prolongation had more comorbidities that are risk factors for QTc prolongation.

Incidence, risk factors, and outcomes of warfarin-associated major bleeding in Thai population.

PURPOSE: This study aimed to describe incidence, risk factors, and outcomes of warfarin-associated major bleeding (WAMB) in Thai patients. METHOD: A nested case-control study was conducted in a cohort of adult patients receiving ≥6 months of warfarin therapy who were prospectively followed up at a tertiary care hospital in Thailand during January 2011 to December 2014. Logistic regression was used to identify risk factors associated with WAMB. The area under the receiver operating characteristic (AUROC) curve was used to assess the performance of the HAS-BLED score to predict WAMB in patients with non-valvular atrial fibrillation (NVAF). RESULTS: Among 1604 patients (2972 patient-year of follow-up), there were 93 major bleeding that occurred in 76 patients. The incidence of WAMB was 3.13 events per 100 patient-year. Time in therapeutic range (TTR) of <60% (RR: 3.62, 95% CI: 1.94-6.73, P < 0.001), mechanical valve replacement at mitral position (RR 3.43, 95% CI: 1.92-6.16, P < 0.001) cancer (RR: 2.84, 95% CI: 1.11-7.29, P = 0.029), and age ≥ 65 years (RR: 2.37, 95% CI: 1.20-4.67, P = 0.012) were independent risk factors for WAMB. There were 17 fatalities and 12 cases of disabilities from WAMB. Mean cost of WAMB was 45 341.54 THB/event. An exploratory analysis suggested that HASBLED score demonstrated an excellent discriminatory capacity to predict WAMB among NVAF patients (AUROC of 0.91, 95% CI: 0.85-0.97, P < 0.001). CONCLUSION: WAMB in Thai population is common and associated with high rate of morbidity and mortality. Improvement in anticoagulation control is clearly needed.