Group: antimycobacterial agent
Capsule or tablet 150 mg, 300 mg

General information

A semisynthetic derivative of rifamycin, a complex macrocyclic antibiotic that inhibits ribonucleic acid synthesis in a broad range of microbial pathogens. It has bactericidal action and a potent sterilizing effect against tubercle bacilli in both cellular and extracellular locations.

Rifampicin is lipid-soluble. Following oral administration, it is rapidly absorbed and distributed throughout the cellular tissues and body fluids; if the meninges are inflamed, significant amounts enter the cerebrospinal fluid. A single dose of 600 mg produces a peak serum concentration of about 10 micrograms/ml in 2-4 hours, which subsequently decays with a half-life of 2-3 hours. It is extensively recycled in the enterohepatic circulation, and metabolites formed by deacetylation in the liver are eventually excreted in the faeces.

Since resistance readily develops, rifampicin must always be administered in combination with other effective antimycobacterial agents.

Clinical information

Uses

A component of all 6- and 8-month anti-tuberculosis chemotherapeutic regimens currently recommended by WHO (see pages 12 and 13).

Dosage and administration

Rifampicin should preferably be given at least 30 minutes before meals, since absorption is reduced when it is taken with food.

Adults and children: 10 mg/kg (maximum 600 mg) daily or three times weekly.

Contraindications

• Known hypersensitivity to rifamycins.
• Hepatic dysfunction.

Precautions

Serious immunological reactions resulting in renal impairment, haemolysis or thrombocytopenia are on record in patients who resume taking rifampicin after a prolonged lapse of treatment. In this rare situation it should be immediately and definitively withdrawn.

Careful monitoring of liver function is required in the elderly and in patients who are alcohol-dependent or have hepatic disease.

Patients should be warned that treatment may produce reddish coloration of urine, tears, saliva and sputum, and that contact lenses may be irreversibly stained.

Use in pregnancy

Whenever possible, the 6-month regimen based upon isoniazid, rifampicin and pyrazinamide should be used.

Vitamin K should be administered to the infant at birth because of the risk of postnatal haemorrhage.

Adverse effects

Rifampicin is well tolerated by most patients at currently recommended doses, although gastrointestinal intolerance can be unacceptably severe. Other adverse effects (skin rashes, fever, influenza-like syndrome and thrombocytopenia) are more likely to occur with intermittent administration. Temporary oliguria, dyspnoea and haemolytic anaemia have also been reported in patients taking the drug three times weekly. These reactions usually subside if the regimen is changed to one with daily dosage.

Moderate rises in serum concentrations of bilirubin and transaminases, which are common at the outset of treatment, are often transient and without clinical significance. However, dose-related hepatitis can occur, which is potentially fatal. It is consequently important not to exceed the maximum recommended daily dose of 10 mg/kg (600 mg).

Drug interactions

Rifampicin induces hepatic enzymes, and may increase the dosage requirements of drugs metabolized in the liver. These include corticosteroids, steroid contraceptives, oral hypoglycaemic agents, oral anticoagulants, phenytoin, cimetidine, quinidine, ciclosporin and digitalis glycosides. Patients should consequently be advised to use a nonhormonal method of birth control throughout treatment and for at least 1 month subsequently.

Biliary excretion of radiocontrast media and sulfobromophthalein sodium may be reduced and microbiological assays for folic acid and vitamin B₁₂ disturbed.

Overdosage

Gastric lavage may be of value if undertaken within a few hours of ingestion. Very large doses may depress central nervous function. There is no specific antidote and treatment is supportive.

Storage

Capsules and tablets should be kept in tightly closed containers, protected from light.