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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RIFADIN (RIFADIN).
| Breastfeeding | Rifampin is excreted in breast milk; M/P ratio ~0.2. Infant exposure ~1-2% of maternal dose. Considered compatible with breastfeeding; monitor infant for jaundice or GI upset. |
| 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 |
■ 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 rifamycins; active liver disease; history of rifampin-induced liver injury; concomitant use with saquinavir/ritonavir (boosts toxicity).
| 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. |
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| 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. |