Rifampin

Category: pharmacological

Aliases: Rifampicin, Rifadin

Pharmacological Mechanism

Bactericidal — binds bacterial RNA polymerase β-subunit. Most potent CYP3A4 inducer in clinical use (also CYP2C9, CYP2C19, CYP2B6, UGT, P-gp via PXR activation). Dramatically lowers warfarin, OCs, methadone, statins, transplant immunosuppressants, anti-HIV agents.

Half-Life (t½)

PO: 3.57h, IV: 3.57h

Dosing Guidelines

PO: Typical 600 mg (Range: 300–600 mg)

Target Organ Systems

cardiovascular
digestive
immune-hematologic

Interactions

Warfarin (major): CYP2C9 induction. Hammond 2022 systematic review (PMID:35152432): 17 studies show warfarin AUC reduced 15-74% with rifampin; warfarin dose increases of 3-5× pre-rifampin dose required to maintain INR. Use midpoint induction_factor 2.5×.
Ethinyl Estradiol (contraindicated): CYP3A4 + UGT induction → contraceptive failure. Bolt 1980 (PMID:7189454): rifampin 450-600 mg/d reduced EE AUC from 1747 to 1014 pg/mL·h (42% reduction → ke induction 1.72×); t½ shortened from 6.3 to 2.9 h. Backup contraception required during + 4 weeks after rifampin.
Midazolam (contraindicated): CYP3A4 induction (gut + liver). Backman 1996 (PMID:8549036) n=10 healthy crossover, rifampin 600 mg/d × 5d then 15 mg PO midazolam d6: oral midazolam AUC dropped 96% (10.2→0.42 µg·min/mL). Factor 10.2/0.42 = 24.3. Renders oral midazolam ineffective; combination is label-contraindicated.
Atorvastatin (major): CYP3A4 induction. Backman 2005 (PMID:16084850) n=10 randomized crossover, rifampin 600 mg/d × 5d + atorvastatin 40 mg single d6: AUC of unchanged atorvastatin acid −80% (95% CI 73-84%, P<.001). Factor 1/0.20 = 5.0. Undermines LDL lowering.
Simvastatin (major): CYP3A4 first-pass induction. Kyrklund 2000 (PMID:11180018) n=10 crossover, rifampin 600 mg × 5d + simvastatin 40 mg d6: parent AUC −87%, simva acid −93% (P<.001). Factor 1/0.13 = 7.7 (parent; conservative — acid form 14×). Cholesterol-lowering effectively abolished.
Cyclosporine (major): CYP3A4 induction (gut + liver). Hebert 1992 (PMID:1424418) n=6, oral 10 mg/kg + IV 3 mg/kg ± rifampin: blood CL 0.30→0.42 L/h/kg (1.4×), F 27%→10% (oral combined drop 3.8×). IV-pure factor 1.4. Author at oral 3.8 — most CsA dosing is PO, transplant rejection risk.
Tacrolimus (major): CYP3A4 + P-gp induction (gut + liver). Hebert 1999 (PMID:9987705) n=6, oral 0.1 mg/kg + IV 0.025 mg/kg/4h ± rifampin × 18d: CL 36→52.8 mL/h/kg (1.47×), F 14.4%→7% — oral combined 3.0×. Threatens graft rejection; close TDM mandatory.
Losartan (warn): CYP2C9 + CYP3A4 induction. Williamson 1998 (PMID:9542475) n=10, losartan 50 mg/d + rifampin 300 mg BID × 1 wk: AUC0-24 −35% (349→225 ng·h/mL, P=0.0001). Factor 1/0.65 = 1.55. Active E-3174 also −40% — moderate efficacy reduction.
Verapamil (contraindicated): CYP3A4 gut-wall induction (extreme). Fromm 1996 (PMID:8855178) n=8, verapamil 120 mg BID × 24d + rifampin 600 mg/d d5-16: oral S-verapamil CL 32× higher (P<.001), F 25× lower. IV CL only 1.3× higher — effect is overwhelmingly first-pass. Author at oral 32; AV-conduction effect abolished.
Oxycodone (major): CYP3A4 induction. Nieminen 2009 (PMID:19417618) verbatim: "Rifampin decreased the area under the oxycodone concentration-time curve of intravenous and oral oxycodone by 53% and 86%, respectively (P < 0.001). Oral bioavailability of oxycodone was decreased from 69% to 21%". 12 healthy volunteers, 4-session paired crossover, rifampin 600 mg/d × 7d + oxycodone IV 0.1 mg/kg / PO 15 mg. PO AUC ratio 0.14 → induction_factor 7.14 (IV ratio 0.47 = 2.13). Analgesia lost.
Buprenorphine (major): CYP3A4 induction. McCance-Katz 2011 (PMID:21596492) verbatim: "Rifampin administration produced significant reduction in plasma buprenorphine concentrations (70% reduction in mean area under the curve (AUC); p=<0.001) and onset of opiate withdrawal symptoms in 50% of participants (p=0.02)". Opioid-dependent subjects on stable BUP/NX × 24h sampling, rifampin 600 mg/d × 15d. AUC ratio 0.30 → induction_factor 3.33. Compare rifabutin: AUC ↓35% (no withdrawal).

Pathways It Modulates

Phase-3 transport (activator) — P-gp + OATP + BCRP induction (PXR-mediated)
Warfarin metabolism (activator) — CYP1A2/2C9/3A4 induction

Chemical Identifiers

PubChem CID: 135398735
Formula: C43H58N4O12
Molecular weight: 822.94 g/mol
InChIKey: JQXXHWHPUNPDRT-WLSIYKJHSA-N
SMILES: C[C@H]1/C=C/C=C(\C(=O)NC2=C(C(=C3C(=C2O)C(=C(C4=C3C(=O)[C@](O4)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)C)O)O)/C=N/N5CCN(CC5)C)/C