Brand name: Zerit

Generic name: stavudine, or d4T

Class: Nucleotide reverse transcriptase inhibitor(nucleotide, NtRTI, or nuke)

Manufacturer: Bristol-Myers Squibb, www.bms.com, (800) 321-1335

AWP: $493.38 (generic $411.16)/month for 40 mg capsules

Standard Dose: One 40 mg capsule twice a day for people weighing 132 pounds or more, or one 30 mg capsule twice a day for people weighing less; with or without food, with no dietary restrictions. It is FDA approved in children from birth on. Zerit is also available in 15 mg, 20 mg, 30 mg, and 40 mg capsules, and a powder for oral solution; check for food restrictions. Dose reduction needed in people with kidney problems. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Generic is available.

Potential side effects and toxicity: Headache, diarrhea, nausea, rash, and peripheral neuropathy (tingling, burning, numbness or pain in the hands or feet) are the most common side effects. Peripheral neuropathy is more common in people who have more advanced HIV or are taking other medications that can cause peripheral neuropathy. It goes away once stavudine is stopped, but can be painful and permanently debilitating if stavudine is not stopped as soon as neuropathy is noticed. Caregivers of young children should be instructed regarding noticing and reporting peripheral neuropathy. Additive lipoatrophy (facial wasting) and mitochondrial toxicities can occur when combined with Videx EC. Adverse reactions and serious laboratory abnormalities in children were similar in type and frequency to those seen in adults. Pancreatitis (inflammation of the pancreas) can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and blood in the urine. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Stop all HIV medications and see a health care provider right away. Your physician will check for pancreatitis by doing blood tests. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid stavudine. Lipoatrophy, fat loss in the face and limbs (arms and legs) and, to a lesser degree, lipohypertrophy (such as "buffalo hump" and increased abdominal fat) has been associated with stavudine. Stavudine and zidovudine (Retrovir) are the HIV drugs most implicated by studies as causing lipoatrophy. Stavudine also seems to be implicated in blood lipid (fat) increases, particularly triglycerides. See chart for potential drug class side effects.

Potential drug interactions: When used in combination with stavudine, drugs such as dapsone, Foscavir (foscarnet), Fungizone (amphotericin B), and Videx EC may increase the risk of developing peripheral neuropathy. Cytovene (ganciclovir), intravenous Pentam (pentamidine), valganciclovir (Valcyte), and Videx EC may increase the risk of pancreatitis. Should be used with caution by people with pre-existing bone marrow suppression, kidney problems, or peripheral neuropathy. Zidovudine and stavudine should not be used together due to evidence that one limits the other's effectiveness. Because of additive neurotoxicity, stavudine should not be combined with Videx EC, if possible.

More information: Stavudine is rarely used in the U.S., due to its toxicity and the availability of newer HIV medications. Contact your health care provider right away if peripheral neuropathy is suspected, but do not stop taking medication unless directed to do so by your health care provider. Studies show that stavudine crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Stavudine is associated with facial wasting, peripheral neuropathy, and pancreatitis, and many leading HIV advocates are adamant that it should be avoided because of these serious, and relatively common, toxicities. See package insert for more complete information on potential side effects and interactions.

Doctor's Comments

I can't think of any reason to use this toxic drug anymore. Even resource-limited countries, where it has been used widely because of its low cost, are trying to move away from d4T. It can cause neuropathy, lipoatrophy, lactic acidosis, and hepatic steatosis (fatty infiltration of the liver). The originally approved dose (40 mg twice a day) was clearly too high, but while d4T might be safer at lower doses, why bother?

-- Joel Gallant, M.D., M.P.H.

Activist's Comments

A very old drug, not used in the United States anymore, and with a list of toxic side effects a mile long; I would steer clear from this one. Unfortunately, it is still used in developing countries, as generics make it a financially attractive agent for cash-strapped governments trying to provide therapies for their populations.

-- Joey Wynn

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