Rifamycins (Rifampin, Rifabutin)

Summary

Rifamycins, which include the drugs rifampin and rifabutin, are a class of antibiotics that are most commonly used to treat mycobacterial infections like tuberculosis. Rifamycins work by inhibiting RNA polymerase, stopping transcription and production of bacterial RNA. Clinically, these drugs are used to treat active TB and are also used to prophylax or prevent infections by Neisseria meningitidis and Haemophilus influenzae in close contacts of infected patients. Notably, rifamycins can cause a harmless red-orange discoloration of bodily fluids. Rifampin but not rifabutin induces CYP enzymes, making it prone to cause drug interactions, especially with HIV medications and warfarin. Another side effect common to all rifamycins is hepatotoxicity.

Key Points

• Rifamycins
  • Drug Names
    • Rifampin
    • Rifabutin
  • Mechanism
    • Inhibits DNA-dependent RNA polymerase
    • Penetrates tissue to reach granulomas
  • Clinical Use
    • Mycobacteria
      • M. tuberculosis (TB)
        • Part of RIPE regimen
      • M. leprae
        • Delays resistance to dapsone when used for leprosy
      • M. avium complex
    • N. meningitidis
      • Used for prophylaxis of close contacts
    • H. influenzae type b
      • Used for prophylaxis of close contacts
  • Adverse Effects
    • Harmless red-orange discoloration of body fluids
      • Can cause orange urine, sweat, saliva, tears
    • Induces CYP450 enzymes (Rifampin)
      • Can cause drug interactions (e.g. warfarin, theophylline, protease inhibitors in HIV)
      • Rifabutin is preferred in HIV patients or patients taking warfarin with TB coinfection
    • Hepatotoxicity
      • Elevations of AST and ALT levels are often seen
    • Nephrotoxicity
      • May cause acute interstitial nephritis
  • Mechanism of Resistance
    • Mutations in RNA polymerase reduce drug binding
      • Monotherapy in TB rapidly leads to resistance