Rifampininteractions

Pharmacodynamic Interactions Healthy subjects who received rifampin 600 mg once daily concomitantly with saquinavir 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted saquinavir) developed severe hepatocellular toxicity. Therefore, concomitant use of these medications is contraindicated. (See CONTRAINDICATIONS.) When rifampin is given concomitantly with other hepatotoxic medications such as halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampin and halothane should be avoided. Patients receiving both rifampin and isoniazid should be monitored closely for hepatotoxicity. Effect of Rifampin on Other Drugs Induction of Drug Metabolizing Enzymes and Transporters Drug metabolizing enzymes and transporters affected by rifampin include cytochromes P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4, UDP-glucuronyltransferases (UGT), sulfotransferases, carboxylesterases, and transporters including P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Most drugs are substrates for one or more of these enzyme or transporter pathways and these pathways may be induced by rifampin simultaneously. Therefore, rifampin may increase the metabolism and decrease the activity of certain coadministered drugs or increase the activity of a coadministered pro-drug (where metabolic activation is required), and has the potential to perpetuate clinically important drug-drug interactions against many drugs and across many drug classes ( Table 1 ). Table 1 summarizes the effect of rifampin on other drugs or drug classes. Adjust dosages of concomitant drugs based on approved drug labeling and if applicable, therapeutic drug monitoring, unless otherwise specified. Table 1. Drug Interactions With Rifampin That Affect Concomitant Drug Concentrations* Drug or Drug Class and Prevention or Management Clinical Effect Antiretrovirals Prevention or Management Concomitant use is contraindicated (see CONTRAINDICATIONS ) Atazanavir Decrease AUC by 72% Darunavir † Substantial decrease in exposure, which may result in loss of therapeutic effect and development of resistance. Tipranavir Fosamprenavir ‡ Decrease AUC by 82% Saquinavir Decrease AUC by 70% Coadministration may result in severe hepatocellular toxicity. Antiretrovirals Prevention or Management Avoid concomitant use Zidovudine Decrease AUC by 47% Indinavir Decrease AUC by 92% Efavirenz Decrease AUC by 26% Hepatitis C Antiviral Prevention or Management Avoid concomitant use Daclatasvir Decrease AUC by 79% Simeprevir Decrease AUC by 48% Sofosbuvir † Decrease AUC by 72% Coadministration of sofosbuvir with rifampin may decrease sofosbuvir plasma concentrations, leading to reduced therapeutic effect of sofosbuvir. Telaprevir Decrease AUC by 92% Systemic Hormonal Contraceptives Prevention or Management Advise patients to change to non-hormonal methods of birth control during rifampin therapy Estrogens Decrease exposure Progestins Anticonvulsants Phenytoin § Decrease exposure § Antiarrhythmics Disopyramide Decrease exposure Mexiletine Decrease exposure Quinidine Decrease exposure Propafenone Decrease AUC by 50% to 67% Tocainide Decrease exposure Antiestrogens Tamoxifen Decrease AUC by 86% Toremifene Decrease steady state concentrations of toremifene in serum Antithrombotic Agents Clopidogrel Prevention or Management Concomitant use of clopidogrel and rifampin should be discouraged Increase active metabolite exposure and risk of bleeding Ticagrelor Prevention or Management Avoid use Decrease exposure Antipsychotics Haloperidol Decrease plasma concentrations by 70% Lurasidone Prevention or Management: Concomitant use is contraindicated (See CONTRAINDICATIONS ) Decrease exposure Oral Anticoagulants Prevention or Management Perform prothrombin time daily or as frequently as necessary to establish and maintain the required dose of anticoagulant Warfarin Decrease exposure Antifungals Fluconazole Decrease AUC by 23% Itraconazole Prevention or Management Not recommended 2 weeks before and during itraconazole treatment Decrease exposure Ketoconazole Decrease exposure Beta-blockers Metoprolol Decrease exposure Propranolol Decrease exposure Benzodiazepines Diazepam *,¶ Decrease exposure Benzodiazepine-Related Drugs Zopiclone Decrease AUC by 82% Zolpidem Decrease AUC by 73% Calcium Channel Blockers ¶ Diltiazem Decrease exposure Nifedipine # Decrease exposure Verapamil Decrease exposure Corticosteroids Þ Prednisolone Decrease exposure Cardiac Glycosides Digoxin Prevention or Management Measure serum digoxin concentrations before initiating rifampin. Continue monitoring and increase digoxin dose by approximately 20% to 40% as necessary. Decrease exposure Digitoxin Decrease exposure Fluoroquinolones Pefloxacin ß Decrease exposure Moxifloxacin *,§ Decrease exposure Oral Hypoglycemic Agents (e.g., sulfonylureas) Glyburide Decrease exposure Rifampin may worsen glucose control of glyburide. Glipizide Decrease exposure Immunosuppressive Agents Cyclosporine Decrease exposure Tacrolimus Prevention or Management Monitoring of whole blood concentrations and appropriate dosage adjustments of tacrolimus are recommended when rifampin and tacrolimus are used concomitantly. Decrease AUC by 56% Narcotic Analgesics Oxycodone Decrease AUC by 86% Morphine Decrease exposure Selective 5-HT3 Receptor Antagonists Ondansetron Decrease exposure Statins Metabolized by CYP3A4 Simvastatin Decrease exposure Thiazolidinediones Rosiglitazone Decrease AUC by 66% Tricyclic Antidepressants Nortriptyline à Decrease exposure Other Drugs Enalapril Decrease active metabolite exposure Chloramphenicol è Decrease exposure Clarithromycin Decrease exposure Dapsone Rifampin has been shown to increase the clearance of dapsone and, accordingly, decrease dapsone exposure. Rifampin has also been shown to increase the production of the hydroxylamine metabolite of dapsone which could increase the risk of methemoglobinemia. Doxycycline ò Decrease exposure Irinotecan Ø Prevention or Management Avoid the use of rifampin, a strong CYP3A4 inducer, if possible. Substitute non-enzyme inducing therapies at least 2 weeks prior to initiation of irinotecan therapy Decrease irinotecan and active metabolite exposure Levothyroxine Decrease exposure Losartan Parent Decrease AUC by 30% Active metabolite (E3174) Decrease AUC by 40% Methadone In patients well-stabilized on methadone, concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms. Praziquantel Prevention or Management Concomitant use is contraindicated (see CONTRAINDICATIONS ) Decrease plasma praziquantel concentrations to undetectable levels. Quinine Prevention or Management Avoid concomitant use Decrease AUC by 75% to 85% Telithromycin Decrease AUC by 86% Theophylline Decrease exposure by 20% to 40% * Administered with rifampin 600 mg daily, unless otherwise specified † Rifampin dosage used concomitantly with the drug(s) is not specified in the proposed package insert. ‡ Administered with rifampin 300 mg daily § Administered with rifampin 450 mg daily ¶ Administered with rifampin 1200 mg daily # Rifampin 1200 mg administered as a single oral dose 8 hours before administering a single oral dose of nifedipine 10 mg Þ Numerous cases in the literature describe a decrease in glucocorticoid effect when used concomitantly with rifampin. The literature contains reports of acute adrenal crisis or adrenal insufficiency induced by the combination of rifampin-isoniazid-ethambutol or rifampin-isoniazid in patients with Addison’s disease. ß Administered with rifampin 900 mg daily à A tuberculosis treatment regimen including rifampin (600 mg/day), isoniazid (300 mg/day), pyrazinamide (500 mg 3 x per day), and the pyridoxine (25 mg) was associated with higher than expected doses of nortriptyline were required to obtain a therapeutic drug level. Following the discontinuation of rifampin, the patient became drowsy and the serum nortriptyline levels rose precipitously (3-fold) into the toxic range. è Concomitant use with rifampin in 2 children ò Administered with rifampin (10 mg/kg daily) Ø Administered with an antibiotic regimen including rifampin (450 mg/day), isoniazid (300 mg/day), and streptomycin (0.5 g/day) IM AUC = area under the time-concentration curve Effect of Other Drugs on Rifampin Concomitant antacid administration may reduce the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of antacids. Concomitant use with probenecid and cotrimoxazole increases the concentration of rifampin which may increase the risk of rifampin toxicities. Monitor for adverse reactions associated with rifampin during coadministration. Other Interactions Atovaquone Concomitant use of rifampin with atovaquone decrease concentrations of atovaquone and increase concentrations of rifampin which may increase the risk of rifampin toxicities. Coadministration of rifampin with atovaquone is not recommended.