rifampin
Brand: Rifadin, Rimactane
Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: rifamycin / antimycobacterial
Organ Systems: infectious-disease
Mechanism of Action
Inhibits the beta subunit of bacterial DNA-dependent RNA polymerase, blocking RNA synthesis and gene transcription; bactericidal; also penetrates biofilms and kills intracellular organisms; one of the most potent CYP inducers in pharmacology.
bacterial DNA-dependent RNA polymerase (beta subunit)
Indications
- tuberculosis (always combined — never monotherapy to prevent resistance)
- LTBI (3-4 months with isoniazid or 4 months alone)
- Staphylococcal prosthetic joint/device infection (adjunctive — not monotherapy)
- meningococcal prophylaxis (close contacts)
- Legionella (combination therapy)
Contraindications
- concurrent saquinavir or ritonavir-boosted saquinavir
- hypersensitivity to rifamycins
Adverse Effects
Common
- hepatotoxicity (elevated LFTs)
- orange-red discoloration of body fluids (urine, sweat, tears, saliva — benign, expected)
- nausea
- rash
- flu-like syndrome (intermittent dosing)
Serious
- fulminant hepatitis (rare)
- thrombocytopenia (intermittent high-dose therapy)
- drug interactions via CYP induction (most significant pharmacological property)
Pharmacokinetics (ADME)
| Absorption | Well absorbed orally (~90%); significantly reduced by food; administer on empty stomach |
| Distribution | Protein binding 80%; Vd ~1 L/kg; excellent intracellular penetration; crosses BBB |
| Metabolism | Hepatic hydrolysis and autoinduction of CYP3A4, CYP2C9, CYP2C19, CYP1A2, CYP2B6 — rifampin is THE most potent CYP inducer |
| Excretion | Biliary/fecal (60%) and renal (30%) |
| Half-life | 2–5 hours (shortens with autoinduction over 1–2 weeks) |
| Onset | CYP induction begins within 24 hours; maximum at 5–7 days |
| Peak | 2–4 hours |
| Duration | 24 hours |
| Protein Binding | 80% |
| Vd | ~1 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| warfarin | CYP2C9/CYP3A4 induction reduces warfarin levels by 60–80%; requires dose doubling; major bleeding risk when stopped | major |
| oral contraceptives | CYP3A4 induction reduces estrogen/progestin levels; contraceptive failure | major |
| antiretrovirals (protease inhibitors, integrase inhibitors) | CYP3A4 induction dramatically reduces levels of most antiretrovirals | major |
Nursing Considerations
- Counsel patients that orange-red discoloration of urine, tears, sweat, and saliva is expected and harmless — but may permanently stain soft contact lenses
- Rifampin is the most potent CYP inducer in clinical practice — review ALL medications before initiating; critical interactions include oral contraceptives, warfarin, antiretrovirals, immunosuppressants, antifungals, and antiepileptics
- Administer 1 hour before or 2 hours after meals for maximum absorption; take at the same time each day
- For TB therapy: NEVER prescribe rifampin as monotherapy — resistance develops within days; always use in combination (RIPE regimen: Rifampin + Isoniazid + Pyrazinamide + Ethambutol)
Clinical Pearls
- Rifampin autoinduces its own CYP3A4-mediated metabolism — within the first 1–2 weeks of therapy, its half-life shortens by 40% as autoinduction reaches maximum, requiring reassessment of dosing intervals
- The CYP induction from rifampin persists for 2–4 weeks after stopping — drug interactions with warfarin and other narrow therapeutic index drugs must be actively managed through the washout period
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.