Rifabutin

MODE OF ACTION OF RIFABUTIN:

Rifabutin acts via the inhibition of DNA-dependent RNA polymerase in gram-positive and some gram-negative bacteria, leading to a suppression of RNA synthesis and cell death.

Drug Label Information | Brands:

Brands of Rifabutin  in Kenya:

Mycobutin®, Pfizer

INDICATIONS:

Rifabutin is indicated for:

– the prophylaxis of M. avium intracellulare complex (MAC) infections in patients with HIV disease with CD4 counts lower than 75 cells/mcl.

– the treatment of non-tuberculous mycobacterial disease (such as that caused by MAC and M. xenopi).

– pulmonary tuberculosis.

DOSAGE AND ADMINISTRATION:

Rifabutin can be administered as a single, daily, oral dose at any time independently of meals.

Posology

Adults

– prophylaxis of M. avium intracellulare complex (MAC) infections in patients with HIV disease with CD4 counts lower than 75 cells/mcl:

300 mg as a single agent.

– treatment of non-tuberculous mycobaterial disease:

450 – 600 mg in combination regimens for up to 6 months after negative cultures are obtained.

When Rifabutin is given in association with clarithromycin (or other macrolides) and/or fluconazole (or related compounds) the Rifabutin dosage may need to be reduced to 300 mg .

– treatment of pulmonary tuberculosis:

150 – 450 mg in combination regimens for at least 6 months.

In accordance with the commonly accepted criteria for the treatment of mycobacterial infections, Rifabutin should always be given in combination with other anti-mycobacterial drugs not belonging to the family of rifamycins.

Paediatric population

There are inadequate data to support the use of Rifabutin in children at the present time.

Elderly

No specific recommendations for dosage alterations in the elderly are suggested.

CONTRAINDICATIONS:

Rifabutin is contraindicated in patients who have had clinically significant hypersensitivity to rifabutin or to any other rifamycins.

ADVERSE DRUG REACTIONS:

Blood and lymphatic system disorders

White blood cell disorders (including agranulocytosis, lymphopenia, granulocytopenia, neutropenia, white blood cell count decreased, neutrophil count decreased), platelet count decreased.

Immune system disorders

Hypersensitivity, bronchospasm, rash, and eosinophilia.

Gastrointestinal disorders

Clostridium difficile colitis/ Clostridium difficile associated diarrhea.

Pyrexia, rash and other hypersensitivity reactions such as eosinophilia and bronchospasm might occur, as has been seen with other antibacterials.

A limited number of skin discoloration have been reported.

Rifamycin hypersensitivity reactions

Hypersensitivity to rifamycins have been reported including flu-like symptoms, bronchospasm, hypotension, urticaria, angioedema, conjunctivitis, thrombocytopenia or neutropenia.

DRUG INTERACTIONS:

Effect of Rifabutin on the Pharmacokinetics of Other Drugs

Rifabutin induces CYP3A enzymes and therefore may reduce the plasma concentrations of drugs metabolized by those enzymes. This effect may reduce the efficacy of standard doses of such drugs, which include itraconazole, clarithromycin, and saquinavir.

Effect of Other Drugs on Rifabutin Pharmacokinetics

Some drugs that inhibit CYP3A may significantly increase the plasma concentration of rifabutin. Therefore, carefully monitor for rifabutin associated adverse events in those patients also receiving CYP3A inhibitors, which include fluconazole and clarithromycin. In some cases, the dosage of rifabutin may need to be reduced when it is coadministered with CYP3A inhibitors.