One 40 mg capsule twice daily

Brand name: Zerit

Common name: stavudine, d4T

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. An approved extended-release (XR) formulation has yet to be manufactured. Take missed dose as soon as possible, but do not double up on your next dose.

AWP: $366 / month for 40 mg

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

AIDS Treatment Information Service: 1 (800) HIV–0440 (448–0440)

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 when combined with Videx or Hivid. 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. 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. Lipodystophy (“buffalo hump”), fat loss (lipoatrophy) in the face and limbs (arms and legs), and central fat accumulation has been associated with Zerit. Zerit and 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 and Vitrasert (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, renal insufficiency or peripheral neuropathy. 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 zalcitabine (Hivid) or ddI.

Tips: Late last year, Zerit was moved from the list of “preferred” drugs to “alternate” drugs, according to U.S. HIV treatment guildlines, “due to increasing reports of stavudine-associated toxicities.” 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. Many leading HIV advocates are adamant that Zerit is associated with facial wasting and should be avoided.

Doctor
Zerit is given twice daily. A once-daily formulation has been approved by the FDA but not released by its manufacturer. Like Videx, its most serious side effects are peripheral neuropathy and pancreatitis. Zerit has been implicated as one of the major causes of lipodystrophy, characterized by loss of facial fat, thinning of the arms and legs due to fat loss, and accumulation of fat on the back of the neck and abdomen. The exact mechanism of this syndrome, however, has not been fully worked out. Stopping Zerit (or any other drug contributing to lipodystrophy) will not reverse the abnormal distribution of fat, but may stop it from progressing.
Activist
My first antiretroviral regimen in 1998 included d4T and ddI—a combination that would be avoided today because of the compounded risk of neuropathy and pancreatitis when the two are used together. In fact, the federal treatment guidelines no longer recommend d4T as a “preferred” drug for people taking their first antiretroviral regimen. It has been implicated for some time—early and loudly in the community—in the development of lipoatrophy (and underlying mitochondrial damage inside cells), and clinical trials eventually verified both. Studies show it’s as effective as other NRTIs, but the price tag is higher—more lipoatrophy, more neuropathy, and greater lipid increases. If you have to take d4T, keep a close eye on your lab values (liver, pancreas) and the mirror—if you notice changes, especially in your face, do…not…ignore…them. Heading off facial wasting and neuropathy is better than any treatments you’ll find for them, at least for now.

Nukes | Retrovir / AZT / zidovudine | Videx, Videx EC / ddI / didanosine |
| Hivid / ddC / zalcitabine | Zerit / d4T / stavudine | Epivir / 3TC / lamivudine |
| Ziagen / abacavir sulfate | Combivir (Retrovir, Epivir) |
| Trizivir (Retrovir, Epivir, Ziagen) | Emtriva / emtricitabine / FTC |
| Viread / tenofovir disoproxil fumarate | Epzicom (Epivir, Ziagen) |
| Truvada (Viread, Emtriva) |

Non-Nukes | Rescriptor / delavirdine | Viramune / nevirapine |
| Sustiva / efavirenz |

HIV Protease Inhibitors | Invirase / saquinavir hard-gel | Crixivan / indinavir | Norvir / ritonavir | Viracept / nelfinavir | Fortovase / saquinavir soft-gel |
| Agenerase / amprenavir | Kaletra (lopinavir/ritonavir) |
| Reyataz / atazanavir | Lexiva / fos-amprenavir | tipranavir |

Fusion Inhibitor | Fuzeon / T-20 / enfuvirtide |

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