Dosing TB drugs in Patients Receiving Dual PIs?

Kathleen E. Squires, MD

Disclosures

April 05, 2000

Question

What is the correct dosage of rifabutin to use daily or biweekly as part of the 2 months' prophylaxis for a positive PPD, when the combination ritonavir/indinavir is used as part of the treatment for HIV?

Diana Franchini, MD

Response from Kathleen E. Squires, MD

As you are aware, there is the potential for significant pharmacologic interactions between the protease inhibitors and the rifamycins due to their effect on the cytochrome P-450 isoenzymes (CYP450). Protease inhibitors are substrates that can either inhibit or induce these isoenzymes (or sometimes exhibit both properties simultaneously). The rifamycins induce CYP450 and therefore can decrease blood levels of the protease inhibitors if administered concomitantly. In turn, concomitant administration of protease inhibitors may affect the blood levels of the rifamycins. Considerable caution must be used when attempting to administer these agents together.

Updated recommendations have just been published that provide guidance in this area.[1] These guidelines revise previous recommendations for the appropriate use of rifampin and rifabutin in the treatment or prophylaxis of tuberculosis in patients receiving protease inhibitor-containing regimens.

Although the use of pyrazinamide and a rifamycin in 2-month regimens for prophylaxis is acknowledged, a 9-month course of isoniazid is endorsed as the preferred option in patients who are receiving protease inhibitors, because of the lack of interaction of this agent with the protease inhibitors. If you choose to use rifabutin as part of a short-course regimen, the recommended dose is 150 mg 2 or 3 times per week when administered in conjunction with a dual protease inhibitor combination containing ritonavir at doses of 100 mg to 600 mg bid. The patient will need to be monitored closely for the known toxicities associated with these agents as well as for unusual or synergistic side effects.

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