Generic Name

Rifampin

Mechanism

• Rifampin acts as a *bactericidal* agent by inhibiting the β subunit of bacterial RNA polymerase.
• This blockade prevents transcription of all mRNA, stopping replication of *Mycobacterium tuberculosis* (Mtb) and other susceptible organisms.
• Its unique mechanism makes it indispensable in combination therapy for TB to limit resistance development.

Pharmacokinetics

• Absorption: Oral bioavailability ~70%; absorption is enhanced with food.
• Distribution: Large volume of distribution; penetrates well into pulmonary tissues, CSF, bone, and abscesses.
• Metabolism & Elimination:
• Hepatically metabolized by phenol‑ether hydroxylation.
• Strong inducer of CYP3A4 and UDP‑glucuronosyltransferases → ↑ clearance of many drugs.
• Half‑life: 3–5 h (shorter with induction).
• 10–20 % excreted unchanged in urine; the remainder conjugated and biliary‑excreted.

Indications

• Active tuberculosis (TB) – pulmonary and extrapulmonary.
• Latent TB infection (LTBI) as part of multi‑drug regimens.
• Meningococcal disease prophylaxis (in combination with ceftriaxone).
• Other mycobacterial infections: leprosy, babesiosis, melioidosis (in selected settings).

Contraindications

• Severe hepatic impairment (ALT/AST > 3× ULN).
• Hypersensitivity to rifampin or other phenolic antimicrobials.
• Pregnancy: Category B – use only if benefits outweigh risks.
• Lactation: Excreted in milk; reduces maternal drug levels and may alter infant drug exposure.
• Drug interactions:
• *CYP3A4* inducers (e.g., carbamazepine, phenytoin) → ↓ efficacy.
• *CYP2C9* substrates (e.g., warfarin) → ↑ anticoagulation risk.
• *CYP3A4* substrates (e.g., statins, macrolides) → ↓ trough levels.

Dosing

• Pulmonary TB (first 2 months): 600 mg PO once daily (or 600 mg + 300 mg PO/bed twice daily).
• LTBI: 300–450 mg PO once daily for 3–4 months.
• MDR‑TB / surgical prophylaxis: Up to 900 mg PO daily in combination regimens.
• Take with food to maximize absorption; avoid concurrent administration of alcohol or high‑fat diets that delay gastric emptying.
• Orange discoloration of bodily fluids starts within 1–2 days; patient counseling is essential.

Adverse Effects

• Common (≥10 %):
• Orange‑red discoloration of urine, sweat, tears, and sputum.
• GI upset (nausea, anorexia, dyspepsia).
• Flu‑like syndrome (fever, chills, myalgia).
• Serious (≤1 %):
• Hepatotoxicity: AST/ALT ↑, jaundice, hepatic failure.
• Hematologic: agranulocytosis, thrombocytopenia.
• Acute renal failure or interstitial nephritis.
• Severe hypersensitivity reactions (rash, eosinophilia).

Monitoring

• Baseline: LFTs (AST, ALT, bilirubin), CBC, renal function, pregnancy testing when indicated.
• During therapy:
• LFTs at 2‑4 weeks, then monthly.
• CBC monthly for first 3 months or as clinically indicated.
• Co‑administered anticoagulants: INR twice weekly for first 2 weeks, then weekly.
• Therapeutic drug monitoring not routinely required but may be considered in MDR‑TB or when drug–drug interactions are significant.

Clinical Pearls

1. Orange Fluid Stains: Patients often unaware of staining; give them a *color guide* card and advise immediate mouth rinse after dosing.

2. Induction Effect on Drugs: Rifampin can reduce serum concentrations of *warfarin*, *statins*, *macrolides*, *protease inhibitors*, and *anti‑epileptics* by 20–50 %. ↙️ Plan dose adjustments or therapeutic drug monitoring.

3. Take With Food, Not Empty Stomach: While rifampin is absorbed better with meals, high‑fat meals can slightly delay peak serum levels; a moderate meal is optimal.

4. Pregnancy & Lactation: Category B; still counsel about potential discoloration, decreased drug levels in milk, and consider alternative TB regimens if severe maternal liver disease.

5. Combination Therapy is Key: Rifampin monotherapy leads to rapid resistance; always pair with *isoniazid, pyrazinamide,* and *ethambutol* for initial 2 months.

6. Adverse‑Event Grading: Grade‑3 hepatotoxicity warrants dose reduction or discontinuation. In grade‑4 cases, immediate cessation and supportive care are mandatory.

7. Drug‑Drug Interaction Log: Maintain a dedicated rifampin interaction sheet in the patient chart for quick reference (e.g., *CYP3A4* inducers, anticoagulants).

8. Re‑dosing After Holding: If therapy is interrupted >2 weeks, restart at full dose – under‑dosing is not safe due to short half‑life and induction.

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• *This concise drug card captures the most critical pharmacologic attributes of Rifampin and is tailored for rapid reference by medical students and clinicians.*