Rifampicin

Action

Inhibits RNA synthesis by blocking RNA transcription in susceptible organisms (mycobacteria and some gram-positive and gram-negative bacteria)

Availability

Capsules: 150 mg, 300 mg

Powder for injection: 600 mg/vial

Indications and dosages

➣ Tuberculosis

Adults: 10 mg/kg/day (up to 600 mg/day) P.O. or I.V. infusion as a single dose

Children: 10 to 20 mg/kg/day (up to 600 mg/day) P.O. or I.V. infusion as a single dose

➣ Asymptomatic Neisseria meningitidis carriers

Adults: 600 mg P.O. or I.V. infusion b.i.d. for 2 days

Children ages 1 month and older: 10 mg/kg/day P.O. or I.V. infusion (up to 600 mg/day) q 12 hours for 2 days

Infants younger than 1 month old: 5 mg/kg P.O. or I.V. infusion q 12 hours for 2 days

Off-label uses

• Mycobacterium avium intracellulare complex infection

• Brucellosis

• Haemophilus influenzae type B

• Severe staphylococcal bone and joint infections

• Prosthetic valve endocarditis caused by coagulase-negative staphylococci

• Leprosy

• Prophylaxis in high-risk close contact of patients with N. meningitidis infections

Contraindications

• Hypersensitivity to drug or other rifamycin derivatives

Precautions

Use cautiously in:

• porphyria

• history of hepatic disease

• concurrent use of other hepatotoxic drugs

• pregnant or breastfeeding patients.

Administration

• Add 10 ml of sterile water to vial to yield a 60-mg/ml solution for I.V. infusion.

• Further dilute in 100 ml of dextrose 5% in water (D₅W) and infuse over 30 minutes, or add to 500 ml of D₅W and infuse over 3 hours.

• Give oral doses with a full glass of water 1 hour before or 2 hours after a meal.

• For an adult who can't swallow capsules or for a young child, mix capsule contents with syrup, shake well, and administer.

• If patient can't receive dextrose, use normal saline solution to dilute. Don't use other I.V. solutions.

Adverse reactions

CNS: ataxia, confusion, drowsiness, fatigue, headache, asthenia, psychosis, generalized numbness

EENT: conjunctivitis; discolored tears, saliva, and sputum

GI: nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, epigastric distress, flatulence, discolored feces, anorexia, sore mouth and tongue, pseudomembranous colitis

GU: discolored urine

Hematologic: eosinophilia, transient leukopenia, hemolytic anemia, hemolysis, disseminated intravascular coagulation (DIC), thrombocytopenia

Hepatic: jaundice

Metabolic: hyperuricemia

Musculoskeletal: myalgia, joint pain

Respiratory: dyspnea, wheezing

Skin: flushing, rash, pruritus, discolored sweat, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome

Other: flulike symptoms, hypersensitivity reactions including vasculitis

Interactions

Drug-drug. Barbiturates, beta-adrenergic blockers, cardiac glycosides, clarithromycin, clofibrate, cyclosporine, dapsone, diazepam, doxycycline, fluoroquinolones (such as ciprofloxacin), haloperidol, levothyroxine, methadone, progestins, quinine, tacrolimus, theophylline, tricyclic antidepressants, zidovudine: increased metabolism of these drugs Chloramphenicol, corticosteroids, disopyramide, efavirenz, estrogens, fluconazole, hormonal contraceptives, itra-conazole, ketoconazole, nevirapine, quinidine, opioid analgesics, oral hypoglycemics, phenytoin, quinidine, ritonavir, theophylline, tocainide, verapamil, warfarin: decreased efficacy of these drugs Delavirdine, indinavir, nelfinavir, saquinavir: decreased blood levels of these drugs

Hepatotoxic drugs (including isoniazid, ketoconazole, pyrazinamide): increased risk of hepatotoxicity

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen, uric acid: increased levels

Dexamethasone suppression test: interference with results

Direct Coombs' test: false-positive result

Folate, vitamin B₁₂ assay: interference with standard assays

Hemoglobin: decreased value

Liver function tests: abnormal values (transient)

Sulfobromophthalein uptake and excretion test: delayed hepatic uptake and excretion

Drug-behaviors. Alcohol use: increased risk of hepatotoxicity

Patient monitoring

• Monitor kidney and liver function tests, CBC, and uric acid level.

☞ Watch for signs and symptoms of bleeding tendency, especially DIC.

• Assess for signs and symptoms of hepatic impairment.

• Monitor bowel movements for diarrhea, which may signal pseudomembranous colitis.

Patient teaching

• Advise patient to take oral dose 1 hour before or 2 hours after meals. If drug causes significant GI upset, instruct him to take it with meals. To further minimize GI upset, teach him to eat small, frequent servings of food and drink plenty of fluids.

☞ Instruct patient to immediately report easy bruising or bleeding, fever, malaise, appetite loss, nausea, vomiting, or yellowing of skin or eyes.

• Tell patient drug may color his tears, urine, and other body fluids reddish or brownish orange. Instruct him not to wear contact lenses during therapy, because drug may stain them permanently.

• Instruct patient not to drink alcohol.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.