Side Effects of Rifampicin
Rifampicin has numerous side effects affecting multiple body systems, with gastrointestinal disturbances, hepatotoxicity, and orange discoloration of body fluids being the most common adverse reactions. 1, 2
Common Side Effects
- Gastrointestinal effects: Heartburn, epigastric distress, anorexia, nausea, vomiting, flatulence, cramps, diarrhea, and pseudomembranous colitis have been reported 1
- Orange discoloration of body fluids: Rifampicin causes universal orange discoloration of urine, tears, sweat, sputum and other body fluids; this can permanently stain soft contact lenses and clothing 3, 1
- Hepatotoxicity: Transient abnormalities in liver function tests, hepatitis, and cholestasis can occur; monitoring of liver enzymes is recommended 1, 2
- Cutaneous reactions: Mild reactions including flushing and itching with or without rash are common and typically self-limiting 1
Serious Side Effects
- Hematologic effects: Thrombocytopenia (especially with high-dose intermittent therapy), leukopenia, hemolytic anemia, decreased hemoglobin, bleeding, and vitamin K-dependent coagulation disorders can occur 1
- Renal effects: Elevations in BUN and serum uric acid are common; rarely, hemolysis, hemoglobinuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure may occur, particularly when therapy is resumed after interruption 1, 4, 5
- Central nervous system effects: Headache, fever, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, behavioral changes, muscular weakness, pains in extremities, and generalized numbness have been observed 1
- Hypersensitivity reactions: These include pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and Drug Reaction with Eosinophilia and Systemic Symptoms syndrome 1
- "Flu-like syndrome": Fever, chills, headache, dizziness, and bone pain may occur, especially with intermittent dosing regimens or when daily administration is resumed after a drug-free interval 1, 6
Drug Interactions
- Enzyme induction: Rifampicin is a potent inducer of hepatic microsomal enzymes, particularly CYP3A4, and can significantly reduce the effectiveness of many medications 7
- Common drug interactions: Rifampicin accelerates the metabolism of:
- Hormonal contraceptives (reduced effectiveness) 1, 2
- Methadone (may cause withdrawal symptoms) 7, 2
- Warfarin and other coumadin derivatives 2, 7
- Glucocorticoids 7
- Oral hypoglycemic agents 7
- Digitalis glycosides 7
- Anticonvulsants 7
- HIV protease inhibitors (contraindicated combination) 2, 7
- Cyclosporin (may cause transplant rejection) 7
Monitoring Recommendations
- Liver function: Regular monitoring of liver enzymes, especially in patients with underlying liver disease, elderly patients, or those consuming alcohol 2
- Complete blood count: Monitor for thrombocytopenia, leukopenia, and anemia 2
- Renal function: Monitor kidney function, particularly when used intermittently or when restarting after interruption 1
- Patient education: Inform patients about orange discoloration of body fluids and potential for permanent staining of contact lenses 1
Risk Factors for Increased Toxicity
- Intermittent dosing: Higher incidence of adverse reactions, including "flu syndrome," hematologic reactions, and renal failure 2, 8
- Resumption after interruption: Increased risk of immunoallergic reactions when therapy is resumed following interruption 8, 6
- Underlying liver disease: Increased risk of hepatotoxicity 2
- Alcohol consumption: May increase risk of hepatotoxicity 2
- Age: Elderly patients may require dose adjustment due to increased risk of adverse effects 2
Patients should be advised to immediately report symptoms such as unusual fatigue, anorexia, nausea, vomiting, dark urine, or jaundice, which may indicate liver toxicity, and to seek immediate medical attention if experiencing shortness of breath, unusual bleeding, or severe skin reactions 2.