rifampicin
antitubercular· Brands: Rifadin, Rimactane, RofactIVPO
Mechanism of action
Rifampicin binds to the beta subunit of bacterial DNA-dependent RNA polymerase, inhibiting RNA synthesis. It is bactericidal against both intracellular and extracellular mycobacteria.
Pharmacokinetics
Well absorbed from the gastrointestinal tract, with peak concentrations reached within 2 to 4 hours. It is extensively metabolised in the liver to the active metabolite desacetylrifampicin, and induces hepatic cytochrome P450 enzymes. Biliary excretion is the main route, with enterohepatic circulation and some renal elimination.
Indications & dosing
Tuberculosis (active)
In combination with other antitubercular drugs; children: 10 mg/kg once daily, max 600 mg.
- adult · PO: 600 mg once daily · In combination with other antitubercular drugs; children: 10 mg/kg once daily, max 600 mg.
Tuberculosis (active)
Maximum daily dose 600 mg; use in combination with other antitubercular drugs.
- pediatric · PO: 10 mg/kg once daily · Maximum daily dose 600 mg; use in combination with other antitubercular drugs.
Latent tuberculosis infection
Given for 4 months as monotherapy; also used with isoniazid for 3 months.
- adult · PO: 600 mg once daily · Given for 4 months as monotherapy; also used with isoniazid for 3 months.
Meningococcal disease prophylaxis
Usually given for 2 days; for children, dose is 10 mg/kg twice daily for 2 days.
- adult · PO: 600 mg twice daily · Usually given for 2 days; for children, dose is 10 mg/kg twice daily for 2 days.
Haemophilus influenzae type b prophylaxis
Given for 4 days to eliminate nasopharyngeal carriage in close contacts.
- adult · PO: 600 mg once daily · Given for 4 days to eliminate nasopharyngeal carriage in close contacts.
Leprosy
In combination with dapsone and clofazimine as multidrug therapy.
- adult · PO: 600 mg once monthly · In combination with dapsone and clofazimine as multidrug therapy.
Contraindications & precautions
- Hypersensitivity to rifampicin or other rifamycins
- Jaundice
- Porphyria
- Severe hepatic impairment · Use with caution, monitor liver function.
- Monitor liver function before and during therapy.
- Warn patients that body fluids may become orange-red and that this is harmless.
- Assess for interactions with other drugs, as rifampicin is a potent enzyme inducer.
- Advise on effective contraception, as rifampicin reduces efficacy of oral contraceptives.
- Avoid in porphyria, unless benefit outweighs risk.
- Monitor for signs of hypersensitivity, especially in the first weeks of treatment.
Adverse effects
- Orange-red discoloration of urine, sweat, tears and other body fluids
- Hepatotoxicity, including elevated transaminases and hepatitisserious
- Gastrointestinal disturbances, such as nausea, vomiting and diarrhoea
- Flu-like syndrome (fever, chills, headache)
- Skin rash
- Thrombocytopeniaserious
- Renal failureserious
- Stevens-Johnson syndrome or toxic epidermal necrolysisserious
Interactions
- methadonemajorAvoid concomitant use if possible. If co-prescription is essential, consider increasing the methadone dose guided by clinical response and monitor for withdrawal symptoms. Monitor plasma methadone concentrations if available. If rifampicin is stopped, reduce the methadone dose as appropriate to prevent toxicity.
- ethinylestradiol/levonorgestrelmajorAvoid co-prescription where possible. If rifampicin is essential, advise a non-hormonal contraceptive method or an alternative contraception (e.g., barrier method or copper intrauterine device) for the entire duration of rifampicin therapy and for at least 28 days after stopping. Monitor for breakthrough bleeding and arrange pregnancy testing if appropriate.
- warfarinmajorAvoid co-prescription where possible. If combination is unavoidable, anticipate a two- to threefold increase in the warfarin dose and monitor INR closely, particularly during the first week of rifampicin therapy and again after rifampicin is stopped. Consider alternative antibiotics with less enzyme-inducing potential or consider alternative anticoagulation strategies, such as a direct oral anticoagulant, where appropriate.
- cyclosporinemajorAvoid co-prescription where possible. If concurrent use is necessary, increase the cyclosporine dose and monitor whole-blood trough levels frequently, adjusting the dose as needed. After stopping rifampicin, reduce the cyclosporine dose and monitor closely to avoid toxicity.
- tacrolimusmajorAvoid concomitant use where possible. If co-administration is unavoidable, increase the tacrolimus dose, guided by frequent trough level monitoring, and adjust therapy when rifampicin is stopped. Consider alternative antitubercular drugs such as rifabutin, which is a weaker inducer, if appropriate.
- phenytoinmajorAvoid the combination if possible. If co-administration is necessary, closely monitor phenytoin plasma concentrations and observe for signs of reduced efficacy. Phenytoin dosage may need substantial upward adjustment, often by two- to three-fold, based on therapeutic drug monitoring. After stopping rifampicin, phenytoin levels may rise, requiring dose reduction to avoid toxicity. Consider alternative antiepileptics or anti-tuberculosis drugs when feasible.
Renal & hepatic adjustment
- Hepatic impairment (mild): No specific dose adjustment required, but monitor liver function.
- Hepatic impairment (moderate): Use with caution; reduce dose based on tolerance, monitor liver function closely.
- Hepatic impairment (severe): Avoid in severe hepatic impairment, especially with jaundice. (avoid)
Monitoring, pregnancy & toxicity
- Liver function tests (AST, ALT, bilirubin) · At baseline, then regularly (e.g., monthly) during treatment
- Full blood count · At baseline, then periodically
- Signs of hepatotoxicity (jaundice, dark urine, fatigue) · Throughout treatment
- Drug interactions (CYP450 inducer) · Review concurrent medications
- Pregnancy: Rifampicin is used to treat tuberculosis in pregnancy; specialist supervision recommended. Evidence suggests it is safe, but weigh benefits against risks.
- Toxicity: Hepatotoxicity (jaundice, elevated liver enzymes) · Stop rifampicin; monitor liver function; provide supportive care.
- Toxicity: Gastrointestinal upset (nausea, vomiting, diarrhoea) · Supportive treatment; consider dose reduction or administration with food.
- Toxicity: Flu-like syndrome (fever, chills, myalgia) with intermittent therapy · Switch to daily dosing or stop therapy; symptomatic treatment.
- Toxicity: Orange-red discoloration of urine, sweat, tears · Inform patient that this is harmless.
Clinical notes
Used in combination with other antitubercular drugs to treat tuberculosis, and alone for prophylaxis of meningococcal disease. Monitor liver function, as hepatitis may occur. May cause orange-red discoloration of urine, sweat, and tears. Potent enzyme inducer, so reduces efficacy of many drugs including oral contraceptives, warfarin, and antiretrovirals.
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BNF; local formulary