RIMACTANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RIMACTANE (RIMACTANE).
Inhibits DNA-dependent RNA polymerase in susceptible bacteria, blocking RNA transcription.
| Metabolism | Primarily hepatic, via deacetylation; also undergoes hydrolysis. Main metabolite: 25-O-desacetylrifampicin. Autoinduction of CYP3A4 and other enzymes. |
| Excretion | Primarily hepatic metabolism to deacetylated metabolite; ~60-65% of dose excreted in feces (biliary), ~15-30% in urine (unchanged and metabolites). Up to 10% via lacrimal, sweat, saliva, and other routes. |
| Half-life | Terminal elimination half-life is 3-5 hours in adults with normal hepatic function; prolonged to 5-10 hours in hepatic impairment or obstructive jaundice. Autoinduction of metabolism reduces half-life by 20-40% after repeated dosing. |
| Protein binding | ~89-91% bound, primarily to albumin. Highly protein-bound, but saturable at high concentrations. |
| Volume of Distribution | Vd ~1.6 L/kg (range 0.9-2.0 L/kg). Extensive distribution into tissues, including lung, liver, and macrophages; penetrates cells (intracellular concentrations exceed serum). |
| Bioavailability | Oral: ~90-95% (absorbed well, but extensive first-pass metabolism reduces systemic bioavailability to ~70-80% with fasting administration; food reduces absorption by 30-50%). Intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours for peak serum concentrations; bacteriostatic action begins within 1-2 hours. Intravenous: peak concentrations immediately, onset within minutes. |
| Duration of Action | Bacteriostatic effect persists for 12-24 hours post-dose; clinical response typically seen within 2-4 weeks of continuous therapy in tuberculosis. Combination therapy required to prevent resistance. |
| Molecular Weight | 822.94 |
| Action Class | RNA polymerase inhibitors- Rifamycins |
| Brand Substitutes | RIFAMPILA 300MG CAPSULE, Macox 300mg Capsule, Osorifa 300mg Capsule, Rifaplus 300mg Capsule, Monocin 450mg Tablet, RF 450mg Tablet, Kemorifa 450mg Tablet, Ramactane 450mg Tablet, Ticin 450mg Tablet |
Rifampin 600 mg orally once daily; intravenous as alternative if oral not possible.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for GFR >10 mL/min; reduce dose by 50% if GFR <10 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% or monitor levels; Child-Pugh C: avoid use or use with extreme caution. |
| Pediatric use | 10-20 mg/kg orally once daily; maximum 600 mg/day. |
| Geriatric use | No specific adjustment; monitor for hepatotoxicity and drug interactions due to age-related changes in liver function and polypharmacy. |
| 1st trimester | Avoid; rifampin is teratogenic in animal studies and associated with limb reductions and other malformations in humans. Use only if no alternative. |
| 2nd trimester | Use with caution; may increase risk of maternal hepatic toxicity and hemorrhage in neonate due to vitamin K deficiency. Monitor PT/INR. |
| 3rd trimester | Use with caution; may cause hemorrhagic disease of the newborn due to vitamin K deficiency. Administer vitamin K to neonate. |
Clinical note
Comprehensive clinical and safety monograph for RIMACTANE (RIMACTANE).
| Placental transfer | Extensive placental transfer; rifampin crosses the placenta achieving fetal serum concentrations approximately 33% of maternal levels. Accumulates in fetal tissues. |
| Breastfeeding | Rifampin is excreted into breast milk in small amounts (maternal dose ~2-4% weight-adjusted). No adverse effects reported in full-term infants. Monitor infant for jaundice, drowsiness, or poor feeding; consider alternative if premature or ill neonate. |
■ FDA Black Box Warning
Severe and potentially fatal hepatotoxicity, including associated with jaundice and death, can occur. Use with caution in patients with pre-existing liver disease or who are heavy alcohol users. Monitor liver function tests frequently.
| Serious Effects |
Hypersensitivity to rifampin or any componentPatients with acute gout (increased uric acid)Concurrent use of ritonavir-boosted protease inhibitors (e.g., saquinavir/ritonavir) for HIV
| Precautions | Hepatotoxicity, especially when used with isoniazid; thrombotic thrombocytopenic purpura (rare); hemolytic anemia; acute renal failure; discontinue if signs of hypersensitivity; may cause reddish discoloration of urine, sweat, sputum, tears, and contact lenses; monitor liver function and CBC. |
| Food/Dietary | Take rifampin on an empty stomach; food decreases absorption. Avoid alcohol due to increased hepatotoxicity risk. |
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| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | RIMACTANE (rifampin) is classified as FDA Pregnancy Category C. Animal studies have shown teratogenic effects (cleft palate, spina bifida) at doses 2-10 times the human dose. Human data are limited; however, rifampin crosses the placenta and has been associated with an increased risk of congenital malformations when used in the first trimester. In the second and third trimesters, rifampin use may be associated with an increased risk of neonatal hemorrhage due to vitamin K deficiency, as well as potential hepatotoxicity in the neonate. The benefit of treating active tuberculosis usually outweighs the risks. |
| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) monthly due to risk of hepatotoxicity. Monitor complete blood count (CBC) for thrombocytopenia and leukopenia. Assess prothrombin time/INR weekly in pregnant women due to risk of hemorrhagic disease of the newborn. Consider vitamin K supplementation (10 mg/day) to the mother in the last month of pregnancy to prevent neonatal hemorrhage. Monitor fetal growth and development via ultrasound if used long-term. |
| Fertility Effects | Rifampin has been reported to cause menstrual irregularities and may decrease the efficacy of hormonal contraceptives due to enzyme induction, potentially affecting fertility. No direct effects on male or female fertility have been conclusively demonstrated in humans, but animal studies showed impaired fertility at high doses. |
| Clinical Pearls | Rimactane (rifampin) is a potent inducer of CYP450 enzymes, reducing efficacy of oral contraceptives, warfarin, and many antiretrovirals. Monitor liver function and signs of hepatotoxicity. Administer on an empty stomach for optimal absorption. Discoloration of urine, sweat, and tears occurs invariably and is benign. |
| Patient Advice | Take this medication on an empty stomach, 1 hour before or 2 hours after meals. · Your urine, sweat, and tears may turn red-orange; this is harmless. · Do not skip doses; complete full course to prevent resistance. · Inform all healthcare providers you are taking rifampin due to drug interactions. · Use backup contraception as rifampin reduces effectiveness of birth control pills. |