Rifampin - Drug Monograph

Introduction

Rifampin (also known as rifampicin) is a semisynthetic bactericidal antibiotic derived from Amycolatopsis rifamycinica. It belongs to the rifamycin class of antibiotics and serves as a cornerstone medication in the treatment of mycobacterial infections, particularly tuberculosis. First introduced in the 1960s, rifampin remains an essential component of modern anti-tuberculosis regimens and has additional applications in treating other bacterial infections.

Mechanism of Action

Rifampin exerts its bactericidal effect by inhibiting DNA-dependent RNA polymerase in susceptible bacteria. Specifically, it binds to the beta subunit of bacterial RNA polymerase, thereby blocking the initiation of RNA transcription. This inhibition prevents bacterial protein synthesis, leading to bacterial cell death. Rifampin is particularly effective against actively dividing microorganisms and demonstrates concentration-dependent killing activity.

Indications

• Pulmonary tuberculosis (as part of combination therapy)
• Asymptomatic Neisseria meningitidis carriers
• Mycobacterium leprae infections (as part of multidrug therapy)

• Non-tuberculous mycobacterial infections
• Prophylaxis for Haemophilus influenzae type b exposure
• Staphylococcal infections (particularly with prosthetic devices)
• Brucellosis (in combination with doxycycline)

Dosage and Administration

• Tuberculosis treatment: 600 mg orally once daily (10 mg/kg, maximum 600 mg)
• Meningococcal prophylaxis: 600 mg orally twice daily for 2 days
• Leprosy: 600 mg orally once monthly (as part of multidrug therapy)

• Hepatic impairment: Reduce dose; monitor closely
• Renal impairment: No adjustment typically needed
• Pediatric dosing: 10-20 mg/kg/day (maximum 600 mg/day)
• Elderly: Use with caution; consider potential comorbidities

• Administer on empty stomach (1 hour before or 2 hours after meals)
• Capsules should be swallowed whole
• Orange-red discoloration of bodily fluids is expected

Pharmacokinetics

Contraindications

• Hypersensitivity to rifampin or other rifamycins
• Concomitant use with saquinavir/ritonavir
• History of severe hepatitis associated with rifampin therapy

Warnings and Precautions

• Hepatotoxicity: Severe and sometimes fatal hepatitis may occur
• Monitor liver function tests regularly

• May cause hematologic abnormalities including thrombocytopenia
• Discoloration of body fluids (urine, sweat, tears) may permanently stain contact lenses
• Use with caution in patients with history of alcoholism or liver disease
• May produce immunosuppression with long-term use
• Can cause vitamin K-dependent coagulation disorders

Drug Interactions

Rifampin is a potent inducer of cytochrome P450 enzymes (CYP3A4, CYP2C9, CYP2C19), leading to numerous clinically significant interactions:

• Anticoagulants: Decreased warfarin effect
• Anticonvulsants: Reduced levels of phenytoin, valproic acid
• Antifungals: Reduced azole antifungal concentrations
• Antiretroviral agents: Significant reduction in protease inhibitor and NNRTI levels
• Cardiovascular drugs: Reduced efficacy of beta-blockers, calcium channel blockers
• Hormonal contraceptives: Decreased effectiveness; recommend alternative contraception
• Immunosuppressants: Reduced cyclosporine, tacrolimus levels
• Oral hypoglycemics: Reduced sulfonylurea efficacy

Adverse Effects

• Gastrointestinal: Nausea, vomiting, diarrhea
• Dermatologic: Rash, pruritus
• Body fluid discoloration: Orange-red urine, sweat, tears
• Hepatitis: Elevated transaminases

• Hepatotoxicity: Fulminant hepatic failure
• Hematologic: Thrombocytopenia, hemolytic anemia
• Renal: Acute interstitial nephritis
• Hypersensitivity reactions: Stevens-Johnson syndrome, anaphylaxis
• Flu-like syndrome: Fever, chills, headache
• Adrenal insufficiency

Monitoring Parameters

• Complete blood count with platelets
• Liver function tests (ALT, AST, bilirubin, alkaline phosphatase)
• Renal function tests
• Hepatitis serology if indicated

• Monthly LFTs for first 3 months, then as clinically indicated
• CBC every 2-4 weeks initially
• Signs/symptoms of hepatotoxicity
• Therapeutic response monitoring
• Adherence assessment

• Visual acuity if long-term therapy
• Vitamin K status with prolonged use
• Drug interaction monitoring with concomitant medications

Patient Education

• Take on empty stomach for optimal absorption
• Expect orange-red discoloration of urine, sweat, and tears
• Do not wear soft contact lenses during therapy
• Report any signs of hepatitis (jaundice, dark urine, fatigue)
• Inform all healthcare providers about rifampin therapy
• Use alternative contraception if using hormonal methods
• Complete full course of therapy even if feeling better
• Store medication properly and check expiration dates
• Report any unusual bleeding or bruising
• Avoid alcohol consumption during therapy

References

1. American Thoracic Society, CDC, and Infectious Diseases Society of America. Treatment of Tuberculosis. MMWR Recomm Rep. 2003;52(RR-11):1-77. 2. Rifampin [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2021. 3. Nahid P, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7):e147-e195. 4. McIlleron H, et al. Complications of antiretroviral therapy in patients with tuberculosis: drug interactions, toxicity, and immune reconstitution inflammatory syndrome. J Infect Dis. 2007;196 Suppl 1:S63-S75. 5. Grosset J, et al. Rifampin: the miracle of a poorly absorbed drug. Int J Tuberc Lung Dis. 2018;22(11):1237-1244. 6. Lexicomp Online. Rifampin drug information. Wolters Kluwer Clinical Drug Information, Inc.; 2023.