Although not U.S. Food and Drug Administration (FDA) approved for Hansen's disease, rifampin is recommended for every manifestation of the disease. It is rapidly bactericidal against M. leprae with bacteriologic success within 3 weeks of starting therapy. Even a single high dose was efficacious in a mouse footpad model. The rifamycins bind to the β-subunit of RNA polymerase in prokaryotic cells and block RNA transcription. Bactericidal activity is observed even in slowly dividing cells, such as Mycobacterium species. Patients may take rifampin once/day unsupervised or once/month supervised, depending on the treatment algorithm. It is readily absorbed with an elimination half-life of ~3 hours. It is available as an intravenous infusion but is rarely used in this fashion for Hansen's disease. There is no dosage adjustment necessary for patients with hepatic dysfunction, but the dose should be reduced by 50% when a patient's creatinine clearance is less than 10 ml/minute as calculated by the Cockcroft-Gault equation. Rifampin is a pregnancy category C drug although not considered a teratogen, and the American Academy of Pediatrics considers rifampin compatible with breastfeeding although it is excreted in breast milk.
Rifampin should never be used as monotherapy because of rapid development of resistance. Point mutations in rpoB, which encodes the β-subunit of RNA polymerase, are the likely mechanism of resistance. Therefore, rifampin is a component of multidrug therapy most commonly paired with dapsone, which reduces the rate of clinical failure resulting from resistance to either component.
Adverse effects of rifampin therapy include rash, hepatotoxicity, and malaise. Patients should be warned of orange discoloration of tears, urine, and sweat, which can stain contact lenses and be disconcerting to the patient. Mild thrombocytopenia is also possible, but this adverse effect rarely requires discontinuation of the drug. Rifampin's rapidly bactericidal activity leads to a proinflammatory state induced by subcellular components of dead bacteria. Therefore, it is contraindicated during the active phase of a reversal reaction. The major issue with rifampin therapy is multiple drug interactions that result from induction of the following cytochrome P450 isoforms: 3A4, 1A2, 2C8, 2C9, 2C19, and 2D6. Pharmacists should check for drug interactions before starting therapy. Rifampin increases the metabolism of dapsone, but this interaction is not significant for the treatment of Hansen's disease. In contrast, the drug interaction between rifampin and prednisone is quite significant, and the rifampin dosage should be reduced from 600 mg/day to 600 mg/month with the addition of corticosteroid therapy.
Pharmacotherapy. 2012;32(1):27-37. © 2012 Pharmacotherapy Publications