rifampin
Rifadin, Rimactane

Available forms
Available by prescription only
Capsules: 150 mg, 300 mg
Injection: 600 mg/vial

Indications and dosages
 Primary treatment in pulmonary tuberculosis. Adults: 600 mg P.O. or I.V. daily as a single dose. Give P.O. dose 1 hour before or 2 hours after meals.
Children: 10 to 20 mg/kg P.O. or I.V. daily as a single dose. Give P.O. dose 1 hour before or 2 hours after meals. Maximum, 600 mg daily. Concurrent administration of other effective antitubercular drugs is recommended. Treatment usually lasts 6 to 9 months.
 Asymptomatic meningococcal carriers. Adults: 600 mg P.O. b.i.d. for 2 days.
Infants and children older than age 1 month: 10 mg/kg P.O. b.i.d. for 2 days.
Neonates younger than age 1 month: 5 mg/kg P.O. b.i.d. for 2 days.
≡ Dosage adjustment. Reduce dosage in patients with hepatic dysfunction.
 Prevention of infection with Haemophilus influenzae type B. Adults and children: 20 mg/kg (up to 600 mg) once daily for 4 consecutive days.
 Leprosy ◇. Adults: 600 mg P.O. once monthly, usually with other drugs.

Pharmacodynamics
Antibiotic action: Rifampin impairs RNA synthesis by inhibiting DNA-dependent RNA polymerase. Rifampin may be bacteriostatic or bactericidal, depending on organism susceptibility and drug level at infection site.
 Rifampin acts against Mycobacterium bovis, M. kansasii, M. marinum, and M. tuberculosis, some strains of M. avium, M. avium-intracellulare and M. fortuitum, and many gram-positive and some gram-negative bacteria. Resistance to rifampin by M. tuberculosis can develop rapidly; rifampin is usually given with other antituberculosis drugs to prevent or delay resistance.

Pharmacokinetics
Absorption: Absorbed completely from the GI tract after oral administration. Food delays absorption.
Distribution: Distributed widely into body tissues and fluids, including ascitic, pleural, seminal, and cerebrospinal fluids, tears, and saliva; and into liver, prostate, lungs, and bone. Drug crosses the placental barrier, and is 84% to 91% protein-bound.
Metabolism: Metabolized extensively in the liver by deacetylation. It undergoes enterohepatic circulation.
Excretion: Undergoes enterohepatic circulation, and drug and metabolite are excreted primarily in bile; drug, but not metabolite, is reabsorbed. From 6% to 30% of rifampin and metabolite appear unchanged in urine in 24 hours; about 60% is excreted in feces. Some drug appears in breast milk. Plasma half-life in adults is 1 1/2 to 5 hours; serum levels rise in obstructive jaundice. Dosage adjustment isn’t needed for patients with renal failure. Rifampin isn’t removed by either hemodialysis or peritoneal dialysis.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with hepatic disease.

Interactions
Drug-drug. Anticoagulants, barbiturates, beta blockers, cardiac glycoside derivatives, chloramphenicol, clofibrate, corticosteroids, cyclosporine, dapsone, disopyramide, estrogens, methadone, hormonal contraceptives, oral sulfonylureas, phenytoin, quinidine, tocainide, verapamil: Decreases effectiveness of these drugs. Monitor patient closely, and adjust dosage if needed.
Hormonal contraceptives: Rifampin inactivates such drugs and may alter menstrual patterns. Advise hormonal contraceptive users to substitute other contraceptive methods.
Isoniazid: Increases hazard of isoniazid hepatotoxicity. Monitor patient closely.
Para-aminosalicylate: May decrease oral absorption of rifampin, lowering serum levels. Administer drugs 8 to 12 hours apart.
Drug-lifestyle. Alcohol use: May increase risk of hepatotoxicity. Discourage alcohol use.

Adverse reactions
CNS: headache, fatigue, drowsiness, behavioral changes, dizziness, ataxia, mental confusion, generalized numbness.
EENT: visual disturbances, exudative conjunctivitis.
GI: epigastric distress, anorexia, nausea, vomiting, abdominal pain, diarrhea, flatulence, sore mouth and tongue, pseudomembranous colitis, pancreatitis.
GU: hemoglobinuria, hematuria, menstrual disturbances, acute renal failure.
Hematologic: eosinophilia, thrombocytopenia, transient leukopenia, hemolytic anemia.
Hepatic: hepatotoxicity, transient abnormalities in liver function test results.
Metabolic: hyperuricemia.
Musculoskeletal: osteomalacia.
Respiratory: shortness of breath, wheezing.
Skin: pruritus, urticaria, rash.
Other: flulike syndrome, discoloration of body fluids, shock, porphyria exacerbation.

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, bilirubin, and uric acid levels.
• May increase eosinophil count. May decrease hemoglobin and platelet and WBC counts.

Overdose and treatment
Signs and symptoms of overdose include lethargy, nausea, and vomiting; hepatotoxicity from massive overdose includes hepatomegaly, jaundice, elevated liver function studies and bilirubin levels, and loss of consciousness. Skin, urine, sweat, saliva, tears, and feces may have red-orange discoloration.
 Treat with gastric lavage followed by activated charcoal; if needed, force diuresis. Perform bile drainage if hepatic dysfunction persists beyond 24 to 48 hours.

Special considerations
 ALERT Don’t confuse rifampin with rifabutin or rifapentine.
• Obtain specimens for culture and sensitivity testing before giving first dose, but don’t delay therapy; repeat tests periodically to detect drug resistance.
• Give drug 1 hour before or 2 hours after meals for maximum absorption; capsule contents may be mixed with food or fluid to enhance swallowing.
• Reconstituted solution is stable for 24 hours at room temperature. Use infusion solutions of 100 to 500 ml within 4 hours.
• Increased liver enzyme activity inactivates certain drugs, especially warfarin, corticosteroids, and oral hypoglycemics, requiring dosage adjustments.
• Observe patient for adverse reactions, and monitor hematologic studies, renal and liver function studies, and serum electrolyte levels to minimize toxicity. Watch for evidence of hepatic impairment, such as anorexia, fatigue, malaise, jaundice, dark urine, and liver tenderness.
• Rifampin alters standard serum folate and vitamin B₁₂ assays.
• Rifampin may cause temporary retention of sulfobromophthalein in the liver excretion test; it also may interfere with contrast material in gallbladder studies and urinalysis based on spectrophotometry.
Breast-feeding patients
• Drug may appear in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety in children younger than age 5 hasn’t been established.
Geriatric patients
• Usual dose in geriatric and debilitated patients is 10 mg/kg once daily (not to exceed 600 mg/day). Monitor renal function closely because elderly patients may be more susceptible to toxic effects.

Patient education
• Explain disease process and rationale for long-term therapy.
• Teach signs and symptoms of hypersensitivity and other adverse reactions, and emphasize need to report them if they occur; urge patient to report any unusual reactions.
• Urge patient to comply with prescribed regimen, not to miss doses, and not to discontinue drug without medical approval. Explain importance of follow-up appointments.
• Encourage patient to report promptly any flulike signs or symptoms, weakness, sore throat, loss of appetite, unusual bruising, rash, itching, tea-colored urine, clay-colored stools, or yellow discoloration of eyes or skin.
• Explain that drug turns all body fluids red-orange; advise patient of possible permanent stains on clothes and soft contact lenses.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use