Zerit

Common Name: stavudine or d4T

Brand Name: Zerit

Class: nucleoside analogs (also called nucleoside reverse transcriptase inhibitors, NRTIs or nukes)

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, and no food restrictions. 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. Generic now available. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $456.16 (generic $411.16) / month for 40 mg capsules

Manufacturer contact: Bristol-Myers Squibb,
www.bmsvirology.com, 1 (800) 272-4878

Potential side effects and toxicity: Peripheral neuropathy (tingling, burning, numbness or pain in the hands or feet) may go away once Zerit is stopped, but can be painful and permanently debilitating if not treated in time. 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. Adverse reactions and serious laboratory abnormalities in children were similar in type and frequency to those seen in adults. Other side effects may include headache, chills/fever, malaise (general ill feeling), insomnia, anxiety, depression, rash, upset stomach (nausea and vomiting), diarrhea, and abdominal pain. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged, fatty liver. 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 Zerit. Lipoatrophy, fat loss in the face and limbs (arms and legs) and, to a lesser degree, lipohypertrophy (such as "buffalo hump" and increase in abdominal girth) has been associated with Zerit. Zerit and Retrovir (zidovudine, AZT) are the HIV drugs most implicated by studies as causing lipoatrophy. Zerit also seems to be implicated in blood lipid (fat) increases, particularly triglycerides.

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

Tips: Zerit is rarely used in the U.S., due to its toxicity and the availability of newer 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 Zerit 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. Zerit 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. Please see package insert for more complete potential side effects and interactions.

Doctor

Zerit (stavudine, known to most as d4T) was the fourth antiretroviral developed and was approved for use in HIV treatment in 1994. This drug was a very effective antiretroviral, but after years of use, the adverse events associated with the drug virtually stopped the prescription of d4T as part of HAART therapy. These side effects are mainly the cause for the worst rate of fat loss called "lipatrophy," most often noted in the face, arms, and legs. There is ongoing concern about the use of this agent in international resource-poor settings due to the low cost availability of this drug. Nevertheless, the side effect profile has led to a widespread avoidance of this drug when affordable alternatives exist. -- Cal Cohen, M.D.

Activist

Once a backbone of many successful regimens, the crippling neuropathy, followed by lipoatrophy (fat loss -- especially in the face and buttocks) have knocked this drug off the preferred list for good reasons. It is truly shameful that this drug continues to be one of the most widely used drugs in resource-poor settings outside of the U.S. -- exporting preventable drug toxicities to the poor, when better drugs are available but cost more. -- Jeff Taylor