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. Take missed dose as soon as possible, but do not double up on your next dose.
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 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 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 is 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 nukes for a long time; and 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, and 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 exeriencing symptoms of pancreatitis and seek immediate medical attention. 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 zidovudine 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. Zidovudine 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:
Contact your healthcare provider immediately if peripheral neuropathy is suspected, but do not stop taking medication unless directed to do so by your healthcare 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
It's strange to think that when Zerit first came out, it was viewed as the less toxic alternative to its chief competitor, AZT. How things have changed! Now we know it's the nuke most likely to cause mitochondrial toxicity, which includes lactic acidosis, hepatic steatosis (fatty liver), and the dreaded lipoatrophy. It's also the most common cause of peripheral neuropathy -- nerve damage in the feet and legs that causes pain and numbness. d4T is still widely used in developing countries because it's cheap and generic, but people there are now experiencing all the same toxicities that people here experienced before we had better alternatives. There are few reasons to use this drug anymore. -- Joel Gallant, M.D.
Activist
Zerit has had a long and troubled history. In its early years, it was viewed with great hope as the long awaited superior replacement for AZT, ddI and ddC. Clinical studies though dragged on longer than expected when it was found that the dose originally studied was too high and had to be adjusted for patient weight. Once this hurdle was overcome and dosing properly understood, Zerit became the favorite of the nucleoside class. It had none of the initial nausea and headaches of AZT and didn't seem to produce much of the pancreatitis and neuropathy caused by ddI. It had a low pill burden and was easy to take. Later, research led to the conclusion that lipodystrophy (fat accumulation) may mostly be caused by protease inhibitors, but lipoatrophy (loss of limb and facial fat) was caused by the nucleoside drugs, and in particular by Zerit. The mechanism was a form of mitochondrial toxicity (mitochondria are energy sources of cells). Scientists learned that mitochondrial toxicity, which could cause lipoatrophy, nerve damage, pancreatitis and even death, was related primarily to drugs that were either thymidine nucleoside analogues like AZT and Zerit, and the "dd" (didioxy…") drugs like ddI and ddC, and Zerit. Thus, Zerit had both the elements responsible for this class of toxicity. Arguments continue to this day about which of the nucleosides cause the greatest degree of these problems and there is conflicting data. Almost overnight, it went from being a key element in nearly all clinical studies to a drug that simply was not used at all. -- Martin Delaney
