Indinavir is a specific inhibitor of the HIV-1 protease, an enzyme essential for the production of mature, infectious virions. It is currently used for the treatment of individuals with HIV-1 infection and is recommended for use in combination with a reverse transcriptase inhibitor to delay emergence of resistance. The drug must be consumed on an empty stomach for maximal absorption. Oral bioavailability is excellent.
Resistance: Resistance to indinavir is mediated by the expression of multiple and variable protease amino acid substitutions. At least two-thirds of indinavir-resistant strains are cross- resistant to saquinavir and ritonavir; however, saquinavir-resistant isolates tend to retain susceptibility to indinavir.
Adverse Effects: The most common adverse effects reported thus far are indirect hyperbilirubinemia and nephrolithiasis. Thrombocytopenia, nausea, diarrhea, and irritability have also been reported in some patients. Indinavir and ritonavir are inhibitors of as well as substrates for cytochrome P450 CPY3A4. Serum levels of indinavir will increase in the presence of antifungal azoles (themselves CYP3A4 inhibitors) and decrease in the presence of rifabutin and rifampin (CYP3A4 inducers). Increased levels of rifabutin (also a CYP3A4 substrate) that result from use of indinavir require a reduction in the rifabutin dosage by 50%. Increased levels of antihistamines, cisapride, and benzodiazepines may also occur with potential toxicity from these drugs. More precise delineation of drug interactions is underway.
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