RIFADIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RIFADIN (RIFADIN).
Inhibits DNA-dependent RNA polymerase in bacterial cells, blocking RNA transcription.
| Metabolism | Primarily hepatic via deacetylation; main metabolite is 25-O-deacetylrifampin. Enterohepatic recirculation occurs. Induces CYP3A4, CYP2C9, and CYP2C19. |
| Excretion | Renal: ~30% unchanged; fecal/biliary: ~60-65% as metabolites (deacetylated form) and unchanged drug; enterohepatic circulation occurs. |
| Half-life | Terminal elimination half-life: 3-5 hours initially, increases to 2-5 hours after repeated dosing due to autoinduction of metabolizing enzymes; in hepatic impairment: up to 5-10 hours. |
| Protein binding | ~80% bound, primarily to albumin. |
| Volume of Distribution | 1.6 L/kg (range 1-2 L/kg); distributes widely into tissues, including lungs, liver, and macrophages; penetrates CSF only when meninges are inflamed. |
| Bioavailability | Oral: 90-95% (well absorbed); food reduces absorption by ~30%. |
| Onset of Action | Oral: 1-2 hours; IV: within 30-60 minutes (time to therapeutic serum concentrations). |
| Duration of Action | Oral: 12-24 hours (bactericidal effect persists despite falling serum levels due to post-antibiotic effect); IV: similar to oral; hepatic impairment may prolong. |
| Molecular Weight | 822.94 |
600 mg orally or intravenously once daily, or 10 mg/kg/day (max 600 mg) for tuberculosis; for meningococcal prophylaxis, 600 mg orally twice daily for 2 days.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR >30 mL/min; for GFR 10-30 mL/min, reduce dose by 50%; for GFR <10 mL/min, use with caution and reduce dose to 50% of normal if necessary. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or reduce to 25% of normal dose with close monitoring. |
| Pediatric use | 10-20 mg/kg/day orally or intravenously once daily (max 600 mg/day) for tuberculosis; for meningococcal prophylaxis, 10 mg/kg/dose (max 600 mg) twice daily for 2 days. |
| Geriatric use | No specific dose adjustment; use with caution due to age-related decline in hepatic function; monitor for hepatotoxicity and drug interactions. |
| 1st trimester | Generally considered safe; no evidence of teratogenicity in humans, but use only if clearly needed. Rifampin crosses placenta and may cause hemorrhagic disease in neonates if used near term. |
| 2nd trimester | Safe for use when indicated; monitor for maternal hepatotoxicity. |
| 3rd trimester | Safe for use when indicated; may increase risk of postpartum hemorrhage in mother and neonatal hemorrhagic disease due to vitamin K antagonism; administer vitamin K to neonate. |
Clinical note
Comprehensive clinical and safety monograph for RIFADIN (RIFADIN).
| Placental transfer | Crosses placenta readily; cord blood concentrations reach up to 33% of maternal serum levels. |
| Breastfeeding | Rifampin is excreted into breast milk in small amounts (<0.05% of maternal dose). American Academy of Pediatrics considers compatible with breastfeeding. Monitor infant for jaundice, drowsiness, or feeding problems. |
■ FDA Black Box Warning
Severe and fatal hepatotoxicity, including hepatitis and jaundice, has been reported. Hepatic function monitoring is required. Re-administration after liver injury is contraindicated.
| Serious Effects |
Hypersensitivity to rifamycinsAcute liver disease (including jaundice)Concurrent use with atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir (due to CYP3A4 induction causing subtherapeutic levels)Concurrent use with voriconazole (rifampin reduces voriconazole levels)
| Precautions | Hepatotoxicity (monitor LFTs); hepatorenal syndrome; thrombocytopenia (idiosyncratic); hypersensitivity reactions; interference with oral contraceptives and many other drugs; orange-red discoloration of body fluids; immune-mediated reactions with intermittent therapy. |
| Food/Dietary | Food reduces the absorption of rifampin; take on an empty stomach with a full glass of water. Avoid alcohol due to hepatotoxicity risk. |
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| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | First trimester: Limited human data, but animal studies show fetal harm (craniofacial defects, spina bifida). Avoid unless benefit outweighs risk. Second/third trimester: No known structural teratogenicity; risk of hemorrhagic disease in neonate due to vitamin K antagonism. Use with vitamin K supplementation. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, bilirubin) and complete blood count monthly. Assess for signs of hepatotoxicity or thrombocytopenia. In pregnancy, monitor INR if on anticoagulation; administer vitamin K 10 mg IM to neonate at birth. |
| Fertility Effects | No evidence of impaired fertility based on human and animal data; may reduce efficacy of hormonal contraceptives. |
| Clinical Pearls | Rifadin (rifampin) is a potent inducer of CYP450 and P-glycoprotein, accelerating metabolism of numerous drugs including oral contraceptives, warfarin, and antiretrovirals. Monitor liver function and watch for hepatotoxicity, especially when combined with isoniazid. Red-orange discoloration of urine, sweat, tears, and contact lenses is benign but must be communicated to patients. Use with caution in hepatic impairment; dose adjustment may be needed. Administer on an empty stomach for optimal absorption. |
| Patient Advice | Take rifampin on an empty stomach at least 1 hour before or 2 hours after a meal. · This medication may cause a harmless reddish-orange color in your urine, sweat, tears, and other body fluids; soft contact lenses may be permanently stained. · Avoid alcoholic beverages during treatment due to increased risk of liver toxicity. · Inform your healthcare provider about all medications you take, especially blood thinners, birth control pills, and HIV medications, as doses may need adjustment. · Complete the full course of therapy even if you feel better, and do not skip doses to prevent resistance. |