rifampin and Atrial-Fibrillation

Rifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug's potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events. We report a bleeding episode after termination of the co-administration of rifampicin and warfarin and detail the challenges related to international normalized ratio (INR) monitoring.. A 59-year-old Brazilian woman chronically treated with warfarin for atrial fibrillation (therapeutic INR range: 2.0-3.0) was referred to a multidisciplinary anticoagulation clinic at a university hospital. She showed anticoagulation resistance at the beginning of rifampicin therapy, as demonstrated by repeated subtherapeutic INR values. Three months of sequential increases in the warfarin dosage were necessary to reach a therapeutic INR, and frequent visits to the anticoagulation clinic were needed to educate the patient about her pharmacotherapy and to perform the warfarin dosage adjustments. The warfarin dosage also had to be doubled at the beginning of rifampicin therapy. However, four weeks after rifampicin discontinuation, an excessively high INR was observed (7.22), with three-day macroscopic hematuria and the need for an immediate reduction in the warfarin dosage. A therapeutic and stable INR was eventually attained at 50% of the warfarin dosage used by the patient during tuberculosis therapy.. The present case exemplifies the influence of rifampicin therapy on warfarin dosage requirements and the increased risk of bleeding after rifampicin discontinuation. Additionally, this case highlights the need for warfarin weekly monitoring after stopping rifampicin until the maintenance dose of warfarin has decreased to the amount administered before rifampicin use. In particular, patients with cardiovascular diseases and active tuberculosis represent a group with a substantial risk of drug-drug interactions. Learning how to predict and monitor drug-drug interactions may help reduce the incidence of clinically significant adverse drug events.

Topics: Antibiotics, Antitubercular; Anticoagulants; Atrial Fibrillation; Drug Interactions; Female; Hematuria; Humans; Middle Aged; Rifampin; Tuberculosis, Pulmonary; Warfarin

Anti-tuberculosis treatment can cause significant drug-drug interaction and interfere with effective anticoagulation. However, there is a lack of evidence and conflicting data on the optimal oral anticoagulation in patients treated for tuberculosis. We investigated the safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients on anti-tuberculosis treatment. Patients on concomitant oral anticoagulation and anti-tuberculosis treatment including rifampin were identified from the Korean nationwide healthcare database. Subjects were censored at discontinuation of either anticoagulation or rifampin. The outcomes of interest were major bleeding, death, and ischemic stroke. A total 2090 patients (1153 on warfarin, 937 on NOAC) were included. NOAC users, compared to warfarin users, were older, had a lower prevalence of hypertension, heart failure, ischemic stroke, and aspirin use and a higher prevalence of cancer, with no significant differences in CHA

Topics: Administration, Oral; Anticoagulants; Antitubercular Agents; Atrial Fibrillation; Hemorrhage; Humans; Ischemic Stroke; Rifampin; Stroke; Treatment Outcome; Warfarin

Evidence and guidelines for Non-vitamin K antagonist oral anticoagulants (NOACs) use when prescribing concurrent rifampin for tuberculosis treatment in patients with non-valvular atrial fibrillation (NVAF) are limited.. Using the Korean National Health Insurance Service database from January 2009 to December 2018, we performed a population-based retrospective cohort study to assess the net adverse clinical events (NACE), a composite of ischemic stroke or systemic embolism and major bleeding, of NOACs compared with warfarin among NVAF patients taking concurrent rifampin administration for tuberculosis treatment. After a propensity matching score (PSM) analysis, Cox proportional hazards regression was performed in matched cohorts to investigate the clinical outcomes.. Of the 735 consecutive patients selected, 465 (63.3%) received warfarin and 270 (36.7%) received NOACs. Among 254 pairs of patients after PSM, the crude incidence rate of NACE was 25.6 in NOAC group and 32.8 per 100 person-years in warfarin group. There was no significant difference between NOAC and warfarin use in NACE (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.48-1.14; P = 0.172). Major bleeding was the main driver of NACE, and NOAC use was associated with a statistically significantly lower risk of major bleeding than that with warfarin use (HR, 0.63; 95% CI, 0.40-1.00; P = 0.0499).. In our population-based study, there was no statically significant difference in the occurrence of NACE between NOAC and warfarin use. NOAC use may be associated with a lower risk of major bleeding than that with warfarin use.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Retrospective Studies; Rifampin; Rivaroxaban; Stroke; Tuberculosis; Warfarin

Direct oral anticoagulants, such as apixaban and rivaroxaban, are important for the treatment and prophylaxis of venous thromboembolism and to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Because apixaban and rivaroxaban are predominantly eliminated by cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp), concomitant use of combined P-gp and strong CYP3A4 inhibitors and inducers should be avoided. Physiologically-based pharmacokinetic models for apixaban and rivaroxaban were developed to estimate the net effect of CYP3A induction, P-gp inhibition, and P-gp induction by rifampicin. The disposition of rivaroxaban is more complex compared with apixaban because both hepatic and renal P-gp is considered to contribute to rivaroxaban elimination. Furthermore, organic anion transporter-3, a renal uptake transporter, may also contribute the elimination of rivaroxaban from systemic circulation. The models were verified with observed clinical drug-drug interactions with CYP3A and P-gp inhibitors. With the developed models, the predicted area under the concentration time curve and maximum concentration ratios were 0.43 and 0.48, respectively, for apixaban, and 0.50-0.52 and 0.72-0.73, respectively, for rivaroxaban when coadministered with 600 mg multiple doses of rifampicin and that were very close to observed data. The impact of each of the elimination pathways was assessed for rivaroxaban, and inhibition of CYP3A led to a larger impact over intestinal and hepatic P-gp. Inhibition of renal organic anion transporter-3 or P-gp led to an overall modest interaction. The developed apixaban and rivaroxaban models can be further applied to the investigation of interactions with other P-gp and/or CYP3A4 inhibitors and inducers.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Biological Transport; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Embolism; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Rifampin; Rivaroxaban; Stroke; Venous Thromboembolism

Topics: Aged; Antibiotics, Antitubercular; Anticoagulants; Atrial Fibrillation; Ciprofloxacin; Coronary Artery Bypass; Drug Incompatibility; Female; Humans; Morpholines; Rifampin; Rivaroxaban; Thiophenes