rifampin and Stroke

Besides its well known antibiotic activity rifampicin exerts multiple brain protective functions in acute cerebral ischemia and chronic neurodegeneration. The present mini-review gives an update of the unique activity of rifampicin in different diseases including Parkinson's disease, meningitis, stroke, Alzheimer's disease and optic nerve injury.

Topics: Alzheimer Disease; Animals; Antibiotics, Antitubercular; Brain; Humans; Meningitis; Neuroprotective Agents; Optic Nerve Injuries; Parkinson Disease; Receptors, Glucocorticoid; Rifampin; Stroke

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

Acute porphyria, though rare, has well-known neurological sequelae. Vasospasm rarely complicates exacerbations of acute intermittent porphyria, but has not been previously reported in hereditary coproporphyria. We describe a porphyric crisis in a woman with previously undiagnosed hereditary coproporphyria (triggered by rifampicin), leading to vasospasm and stroke.

Topics: Adult; Brain; Coproporphyria, Hereditary; Female; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Radiography; Rifampin; Stroke; Vasospasm, Intracranial