What is the recommended dosing for Rifampin (rifampicin)?

Rifampin Dosing

Standard Dosing Recommendations

For tuberculosis treatment in adults, rifampin should be administered at 10 mg/kg once daily (maximum 600 mg/day) orally, taken either 1 hour before or 2 hours after a meal with a full glass of water. 1

Adult Dosing by Indication

Tuberculosis:

• Daily regimen: 10 mg/kg once daily, not to exceed 600 mg/day 1
• Twice-weekly regimen: 10 mg/kg per dose (maximum 600 mg) 2
• Three-times-weekly regimen: 10 mg/kg per dose (maximum 600 mg) 2
• Duration: Minimum 6 months for rifampin-based regimens, completing at least 180 daily doses or equivalent intermittent dosing 2

Meningococcal carriers:

• 600 mg twice daily for 2 days 1

Human Granulocytic Anaplasmosis (when doxycycline contraindicated):

• 300 mg twice daily orally for 7-10 days 2

Pediatric Dosing

Tuberculosis:

• 10-20 mg/kg once daily, not to exceed 600 mg/day 1
• The higher end of this range (15-20 mg/kg) is generally preferred to ensure adequate drug exposure 2

Meningococcal carriers:

• Children ≥1 month: 10 mg/kg (maximum 600 mg) every 12 hours for 2 days 1
• Infants <1 month: 5 mg/kg every 12 hours for 2 days 1

Human Granulocytic Anaplasmosis:

• 10 mg/kg twice daily (maximum 300 mg per dose) for 7-10 days 2

Critical Dosing Considerations

Drug Interactions Requiring Dose Adjustment

When rifabutin (not rifampin) is used with antiretrovirals:

• With indinavir, nelfinavir, or amprenavir: Reduce rifabutin dose from 300 mg to 150 mg daily 2
• With efavirenz: Increase rifabutin dose from 300 mg to 450 mg daily 2
• Rifampin itself should generally not be coadministered with protease inhibitors due to severe bidirectional interactions 2

Hepatic Enzyme Induction Effects

• Rifampin is a potent inducer of hepatic cytochrome P450 enzymes (especially CYP3A4) and P-glycoprotein 2, 3
• Full enzyme induction occurs within approximately 1 week of starting treatment 3
• Induction effects dissipate roughly 2 weeks after discontinuation 3
• This necessitates dose adjustments or avoidance of numerous concomitant medications including oral contraceptives, warfarin, immunosuppressants, and many others 2, 4

Pharmacokinetic Properties Affecting Dosing

• Peak serum concentrations of 7-14 mg/mL occur 1.5-3 hours after a 600 mg dose 2
• Approximately 75-80% protein-bound, primarily to albumin 2, 5
• Exhibits dose-dependent pharmacokinetics: doses above 300-450 mg saturate hepatic extraction, resulting in more than proportional increases in serum concentrations 5
• Autoinduction of metabolism occurs with repeated administration, reducing half-life from approximately 2.5 hours initially 5

Special Populations

Renal Impairment

• No dose adjustment required for rifampin in renal insufficiency, as it is primarily hepatically cleared 2
• Can be used safely in end-stage renal disease 2

Hepatic Impairment

• Clearance may be impaired with liver disease, causing increased serum levels 2
• Despite this concern, rifampin should generally be included in tuberculosis regimens due to its critical importance, but with increased frequency of clinical and laboratory monitoring 2

Pregnancy

• Rifampin is considered safe in pregnancy (Category C) 2
• No dose adjustment required 2

Administration Guidelines

Timing and Food Interactions

• Administer 1 hour before or 2 hours after meals with a full glass of water for optimal absorption 1
• Absorption is rapid and practically complete when taken on an empty stomach 5

Extemporaneous Suspension Preparation

For patients unable to swallow capsules:

• Prepare 1% w/v suspension (10 mg/mL) using contents of rifampin capsules mixed with specified syrups 1
• Stable for 4 weeks at room temperature (25±3°C) or refrigerated (2-8°C) 1
• Must shake well prior to administration 1

Common Pitfalls and Contraindications

Never Use as Monotherapy for Non-Mycobacterial Infections

• Rifampin should never be used alone for staphylococcal or other bacterial infections due to rapid development of resistance (approximately 30% rate) 2, 6
• When used for MRSA infections, must always be combined with another active antibiotic 2

Inappropriate Uses

• Not recommended for skin and soft tissue infections (cellulitis) either as monotherapy or adjunctive therapy (IDSA Class A-III recommendation) 4
• Lack of adequately powered clinical data establishing benefit in MRSA skin infections 2, 4

Dosing Variability in Literature

• Published rifampin dosing for MRSA infections varies widely from 600 mg daily (single or divided dose) to 900 mg daily in 2-3 divided doses 2
• This variability reflects lack of definitive optimal dosing studies for non-tuberculosis indications 2
• The ranges suggested in guidelines are based on limited data and expert opinion 2

Monitoring Requirements

• No routine laboratory monitoring required specifically for rifampin 2
• However, monitor for drug interactions that may necessitate measurement of serum concentrations of concomitant medications 2
• Patients should be advised that rifampin colors urine, tears, sweat, and other body fluids orange and may permanently discolor soft contact lenses 2