Drug Detail

Rifampicin

Last Updated June 10, 2016

Trade Names

Drug Classification

Broad spectrum semisynthetic rifamycin antimycobacterial

Formulations

  • Rifampicin: 150 mg, 600 mg capsules; 450 mg, 600 mg tablets; 300 mg/vial powder for reconstitution and further dilution for intravenous injection;
  • Rifampicin/isoniazid: 150/75 mg tablets, 300/150 mg tablets, 60/60 mg tablets;
  • Rifampicin/isoniazid/pyrazinamide/ethambutol: 150/75/400/275 mg tablets.

Indications and Pharmacology

Indication: treatment of primary tuberculosis in combination with other antituberculosis drugs; also nontuberculous mycobacteria, leprosy, brucellosis, resistant staphylococcal infections.

Mechanism of action: inhibition of DNA-dependent RNA polymerase.

Pharmacokinetics: bioavailability diminished by food. Well absorbed from gastrointestinal tract and widely distributed throughout body; half-life 2-5 hours, prolonged in liver disease. Rapid hepatic metabolism to active deacetylated metabolite.

Dosage

Adult Dose for Tuberculosis: 8-12 mg/kg/day in single oral dose or fixed-dose combination regimen or intravenous infusion over 3 hours, maximum 600 mg/day.

Adult Dose for Brucellosis: 600-900 mg/day for 6 weeks in combination with doxycycline 200 mg/day.

Taking on an empty stomach recommended to maximize absorption, but gastrointestinal tolerance may be improved by taking with food.

Use in Renal or Hepatic Insufficiency: 

  • Renal insufficiency: no more than 10 mg/kg/day.
  • Hepatic insufficiency: no more than 8 mg/kg/day.

Use in Pregnancy and Breastfeeding: Pregnancy Category C. Teratogenic effects reported in animals, no adverse effects seen in human foetuses; infants should receive vitamin K at birth due to risk of postnatal haemorrhage.

Low levels excreted in breast milk unlikely to harm nursing infant.

Use in Children: 10-20 mg/kg/day in single dose or fixed-dose combination regimen, maximum 600 mg/day.

For tuberculosis meningitis and miliary tuberculosis: up to 20 mg/kg/day; use caution with high doses in areas with high prevalence of infectious hepatitis.

Warnings

Contraindicated for patients with porphyria; patients with history of hypersensitivity to rifampin, any of the components, or to any rifamycin*; and patients receiving atazanavir, darunavir, saquinavir, fosamprenavir, or tipranavir.*

Use caution in patients with hypersensitivity to rifabutin or any other rifamycins.

May cause liver dysfunction; use with caution in patients with hepatic dysfunction, alcoholism, or acute hepatitis. Hepatotoxicity risk increased by alcohol use or concomitant isoniazid, pyrazinamide, or other potentially hepatotoxic drugs.

Decreased efficacy of oral contraceptives due to enhanced metabolism; replace with injectable progestogen-only contraceptive.

Bodily fluids (eg, urine, tears, sweat) may be coloured red/orange; may cause permanent staining of soft contact lenses.

Drug–Drug Interactions

Activation of pregnane X receptor (PXR) leads to enhanced metabolism of several medications.

Rifampicin induces cytochrome P450 enzyme function and may reduce concentrations and efficacy of many drugs metabolised in liver or intestine, including protease inhibitors, nonnucleoside reverse transcriptase inhibitors, glucocorticosteroids, phenytoin, carbamazepine, theophylline, warfarin, sulphonylurea-type oral antidiabetic drugs, oral contraceptives, progestin implants, cyclosporin, quinine, quinidine, digoxin, beta-blockers, verapamil, methadone, midazolam, itraconazole, ketoconazole.

Increased risk of severe hepatocellular toxicity with concomitant ritonavir-boosted saquinavir.*

Substantially decreased plasma concentration of antivirals: atazanavir, darunavirsaquinavir.

Decreased efficacy of oral contraceptives due to enhanced metabolism; replace with injectable progestogen-only contraceptive.

Considerations for Special Populations

Contraindicated for patients with porphyria.

Use with caution in patients with hepatic dysfunction, alcoholism, or acute hepatitis.

Patients with viral infections: rifampicin affects plasma concentrations and efficacy of several antiviral medications (see above).

See above for pregnancy and lactation.

Adverse Effects

Hepatotoxicity (elevated serum transaminase levels, overt hepatitis, jaundice), gastrointestinal effects (nausea, vomiting, anorexia, mild discomfort, diarrhoea), hypersensitivity reactions, haematologic effects (eosinophilia, thrombocytopenia, leucopenia), central nervous system effects (drowsiness, headache, confusion, muscular weakness), adrenal insufficiency due to increased glucocorticosteroid metabolism.

*Recommendation from US prescribing information