March/April 2009
Common Name: stavudine or d4T
Brand Name: Zerit
Class: nucleoside analog (also called nucleoside reverse transcriptase inhibitor, NRTI, or nuke)
Standard dose: One 40 mg capsule twice a day for people weighing 132 pounds (60 kg) or more, or one 30 mg capsule twice a day for people weighing less; no food restrictions (may be taken with or without food). 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 may be reduced in people with kidney problems. Generic now available. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $456.89 (generic $410.70) / month for 40 mg
Manufacturer contact: Bristol-Myers Squibb,
www.bmsvirology.com, 1 (800) 272-4878
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
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. Additive lipoatrophy (facial wasting) and mitochondrial toxicities can occur when combined with Videx. Caregivers of young children should be instructed regarding noticing and reporting peripheral neuropathy. 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 fatal toxicity with all NRTIs: pancreatitis (inflammation of the pancreas), hepatomegaly with steatosis (enlarged, fatty liver), and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis has been seen in patients taking NRTIs, but is more common and more severe in women, people who are obese, and people who have been taking NRTIs for a long time; it is more common in people with liver disease, but can occur in people without a history of liver damage. Pregnant women should particularly avoid the combination of Zerit and Videx due to the risk of lactic acidosis. People with lactic acidosis may experience persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged, fatty liver. People with a history of peripheral neuropathy, pancreatitis or heavy alcohol use should avoid Zerit. Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting and blood in the urine. Stop taking Zerit immediately if experiencing symptoms of pancreatitis and seek medical attention right away. Your physician will check for pancreatitis by checking for increased levels of amylase and lipase in the blood. Risks for pancreatitis include: higher than recommended doses of NRTIs, advanced HIV, and alcohol use. 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 (the thymidine analogs) 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 now not commonly 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 and many leading HIV advocates are adamant that it should be avoided for this reason. 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 infection in 1994. This drug has had a very long run in the treatment of those infected with HIV. It was and still is a very effective antiretroviral, but after years of use, the adverse events associated with the drug (outlined above) virtually stopped the prescription of d4T as part of HAART therapy. There are still some patients in our clinic (doing well and with no adverse events) who refuse to stop d4T. There are some studies that show low-dose d4T is still effective with fewer adverse events. This data has not persuaded many health care providers treating HIV to use the drug. Zerit has always been a twice-a-day drug. In 2002, the FDA approved an extended-release formulation of Zerit for once-daily dosing. Zerit XR was used in several important clinical trials, but BMS never brought the drug to market. This company "silence" speaks volumes. In developing countries, d4T is a very important antiretroviral. It is used as first-line therapy in the fixed dose combination called Triomune (lamivudine, stavudine, nevirapine) dosed twice daily. This drug has made a huge impact on the HIV epidemic in Africa, but the many adverse effects associated with long-term use of d4T are now becoming apparent. Often this is the only antiretroviral that is available to those infected with HIV and having AIDS in Africa. Interestingly, in Uganda, the major clinic treating HIV/AIDS (The Joint Clinical Research Centre) and the Ministry of Health are attempting to reduce the use of d4T as part of HAART regimens. The alternative is the fixed dose combination Combivir (see Combivir). -- Frank M. Graziano, M.D., Ph.D.
Activist
Zerit is proof positive that hindsight is indeed 20/20. Once thought to be less toxic than its close rival AZT, Zerit was the great hope for replacing AZT. But over the years data began to show that Zerit was the culprit for the lion's share of nucleoside-associated lipoatrophy (loss of body fat particularly in the face, limbs, and ass) and peripheral neuropathy. Zerit has also been associated with hyperlipidemia (increased levels of LDL, the "bad" cholesterol). Consequently, Zerit has fallen out of grace and favor -- in the U.S. Unfortunately, because it is now available as a cheaper, generic drug, it is being widely used in developing countries highly impacted by HIV/AIDS. I, for one, think that's reprehensible. Believe me, having survived highly dosed AZT monotherapy, I understand that desperation for taking whatever drug may be available, but we know better now, and to pass Zerit along without any improvement in its side effect profile is unconscionable. -- Morris Jackson