Rifabutin

Rifabutin (also known as mycobutin) is effective for the treatment of tuberculosis (TB). It is most commonly used as a replacement for rifampicin, one of the strongest first-line drugs. Rifabutin has been demonstrated to be as effective as rifampicin for TB treatment. A major drawback of rifabutin is its high cost, although in 2009 the U.S. pharmaceutical company Pfizer did agree to lower the cost significantly in developing markets. Rifabutin is the only rifamycin that does not appear to have a significant impact on the p450 exzyme, which is involved in the metabolisation of some antiretrovirals. It is therefore receommended for use with antiretrovirals but it has not been well studied and the dosages for adults and children are not well understood. Dosage ------ _Adults:_ 300 mg orally once a day. If nausea or vomiting becomes a problem, 150 mg orally every 12 hours is an alternative. _Adults with liver damage (creatinine clearance < 30 ml/min):_ 150 mg orally once a day (regular dose should be reduced by 50%). _Children:_ 5 mg/kg/day orally has been used in a limited number of cases. More testing is needed to determine correct dosing. _Notes on dosing:_ - Rifabutin is most often used as an alternative to rifampicin. Therapy normally lasts 18 to 24 months. - Dose adjustments may be necessary when taken with protease inhibitors or non-nucleoside reverse transcriptase inhibitor. The dose should be increased to 450 mg or 600 mg when given with efavirenz. How it works ------------ Rifabutin works by blocking the RNA-polymerase of the bacteria that cause TB infection. RNA polymerase is an enzyme that uses copies of DNA to create RNA transcripts, which are then turned into proteins. By blocking RNA polymerase, Rifabutin prevents bacteria from synthesizing vital proteins. Side effects ------------ Potential side effects of rifabutin include diarrhea, nausea/vomiting, changes in taste, and rash. Rifabutin may cause urine, sweat, or saliva to turn a brown-orange color, which is a harmless but potentially alarming side effect. In rare cases, Rifabutin has been associated with the blood disorder neutropenia. Like all antibiotics, it may cause a severe intestinal condition (Clostridium difficile-associated diarrhea) to develop during treatment, or in the months after treatment has stopped. Clinical studies and approval ----------------------------- Rifabutin was discovered by scientists at the drug company Achifar in 1975, and was approved by the FDA in 1992. It is now recommended by the WHO as a first-line treatment for TB. It was added to the Essential Medicines List by the WHO in 2009. Multiple studies have shown that rifabutin and rifampicin are similarly effective for the treatment of active TB, with some evidence that rifabutin may cause the conversion of sputum from positive to negative to occur more quickly than rifampicin.[^Grassi] More studies, particularly those that include HIV/TB co-infected patients and elderly patients, are needed to determine when and how rifabutin should be administered. A major benefit of rifabutin is that it has fewer drug-drug interactions than rifampicin. Rifampicin interacts with certain antiretroviral medications such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors. In HIV positive patients taking these drugs, rifabutin is usually a safer medication to use. However, rifabutin therapy has important drawbacks that should be considered before prescribing the medication. Firstly, some antiretroviral drugs can affect rifabutin concentrations in the body. For patients taking antiretroviral therapy, healthcare providers must follow a set of somewhat complex guidelines for the proper administration of rifabutin. Secondly, the changes in rifabutin dosage can be problematic in patients that stop taking the antiretroviral medications that interact with rifabutin. This is because the rifabutin dose may lose its effectiveness in these patients.[^CDC] Advocacy issues --------------- - Until recently, rifabutin was too expensive for use in many countries. In 2009, the U.S. pharmaceutical company Pfizer agreed to a deal, brokered by the Clinton HIV/AIDS initiative, to lower the price of rifabutin by 60 percent of the price in Western countries at the time. The price was made available throughout developing markets in Africa, Asia, Eastern Europe, the Middle East, and the Caribbean. The drug is no longer protected by patent, and is sold by at least two other generic manufacturers, Lupin of India and Med Shine Pharma of China. - Further research is needed to establish the safety and efficacy for elderly and pediatric patients. [^Grassi]: C Grassi et al. Use of Rifabutin in the Treatment of Pulmonary Tuberculosis. Clinical Infectious Diseases. 1996; 22 (Suppl 1). [^CDC]: Centers for Disease Control and Prevention. [Managing Drugs Interactions in the Treatment of HIV-related Tuberculosis](http://www.cdc.gov/tb/publications/guidelines/tb_hiv_drugs/rifabutin_therapy.htm "CDC"). July 2010.