Stavudine

Stavudine (d4T, Zerit) is a thymidine nucleoside analogue that is active against HIV-1 and HIV-2. It is approved for the therapy of HIV infection as part of a multidrug regimen and is also used for postexposure prophylaxis.

The adverse effects with which stavudine is most frequently associated are headache, diarrhea, skin rash, nausea, vomiting, insomnia, anorexia, myalgia, and weakness. Peripheral neuropathy consisting of numbness, tingling, or pain in the hands or feet is also common with higher doses of the drug. Significant elevation of hepatic enzymes may be seen in approximately 10 to 15% of patients. Lactic acidosis occurs more frequently with stavudine than with other NRTIs. Viral resistance to stavudine may develop, and cross-resistance to zi-dovudine and didanosine may occur.

Stavudine should be used with caution in patients at risk for hepatic disease and those who have had pancreatitis. Persons with peripheral neuropathy, the elderly, and those with advanced HIV disease are at increased risk for neurotoxicity. Dosage adjustment is required for patients with renal insufficiency.

Stavudine possesses several clinically significant interactions with other drugs. Although hydroxyurea enhances the antiviral activity of stavudine and didano-sine, combination therapy that includes stavudine and didanosine, with or without hydroxyurea, increases the risk of pancreatitis. Combinations of stavudine and di-danosine should not be given to pregnant women because of the increased risk of metabolic acidosis. Zidovudine inhibits the phosphorylation of stavudine; thus, this combination should be avoided.

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