What are the potential side effects of Rifampin (rifampicin)?

Rifampin Side Effects

Rifampin can cause significant side effects including hepatotoxicity, drug interactions, thrombocytopenia, and "flu-like syndrome," with hepatotoxicity being the most serious concern requiring monitoring of liver function during treatment. 1, 2

Common Side Effects

• Gastrointestinal effects:

  • Abdominal distress
  • Nausea
  • Vomiting
  • Diarrhea
  • Anorexia 1

• Orange-red discoloration:

  • Urine
  • Sweat
  • Tears
  • Saliva
  • Feces
  • Can permanently stain soft contact lenses 1, 2

• Hepatic effects:

  • Transient elevation of liver enzymes
  • True hepatitis (more common when combined with isoniazid) 1, 2

Serious Side Effects

Hepatotoxicity

• Hepatitis occurs in approximately 1-2% of patients 3
• Risk factors include:
  • Pre-existing liver disease
  • Concurrent use with isoniazid (increases risk to 3-4%) 1
  • Alcohol consumption
  • Age (higher risk in older patients) 1
• Usually appears within first 2 weeks of treatment 1
• May present as cholestatic or hepatocellular damage 2

Immunologic/Hematologic Reactions

• More common with intermittent dosing than daily regimens 1
• Include:
  • Thrombocytopenia (particularly with high-dose or intermittent therapy)
  • Hemolytic anemia
  • Thrombotic microangiopathy (including thrombotic thrombocytopenic purpura)
  • Acute renal failure
  • Shock 2

"Flu-like Syndrome"

• Fever, chills, headache, and malaise
• More common with:
  • Intermittent dosing regimens
  • Doses >600mg given once or twice weekly
  • Irregular medication intake 1, 2

Other Serious Reactions

• Cutaneous reactions (rash, pruritus)
• Hypersensitivity reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Pulmonary toxicity (interstitial lung disease, pneumonitis)
• Acute renal failure 2

Drug Interactions

Rifampin is a potent inducer of hepatic enzymes, particularly CYP3A4, and affects drug transporters like P-glycoprotein. This leads to numerous clinically significant drug interactions 4:

• Decreased effectiveness of:
  • Oral contraceptives (women should be advised to use alternative contraception) 1
  • Anticoagulants (warfarin)
  • Methadone (can precipitate withdrawal in patients on maintenance therapy)
  • Corticosteroids
  • Antiepileptics (phenytoin, carbamazepine)
  • Cardiovascular medications (digoxin, verapamil, calcium channel blockers)
  • HIV protease inhibitors (contraindicated)
  • Immunosuppressants (cyclosporin, tacrolimus)
  • Sulfonylureas
  • Theophylline 1, 4

Monitoring Recommendations

1. Baseline assessment:

   • Liver function tests (ALT, AST, bilirubin)
   • Complete blood count
   • Renal function tests 1

2. During treatment:

   • Monitor for symptoms of hepatitis (anorexia, nausea, vomiting, jaundice, dark urine)
   • Periodic liver function tests, especially in patients with risk factors
   • Discontinue immediately if signs of hepatotoxicity develop 1, 2

3. Special precautions:

   • Use with caution in patients with pre-existing liver disease
   • Avoid in patients with jaundice
   • Avoid concurrent use with other hepatotoxic drugs 1

Important Considerations

• Full enzyme induction occurs within about 1 week of starting rifampin and takes approximately 2 weeks to dissipate after discontinuation 4
• Patients should be instructed to take rifampin either 1 hour before or 2 hours after meals with a full glass of water 2
• Patients should be warned about bodily fluid discoloration to prevent unnecessary concern 2
• Hepatotoxicity risk is higher when rifampin is combined with pyrazinamide for treatment of latent tuberculosis infection 1

Remember that rifampin is a cornerstone drug for tuberculosis treatment, and despite these potential side effects, the benefit usually outweighs the risks when properly monitored in appropriate clinical situations.