Brand name: Ziagen

Common name: abacavir sulfate

Class: nucleoside analog (also called nucleoside reverse transcriptase inhibitor, NRTI, or nuke)

Standard dose: One 300 mg tablet twice a day, with or without food. Strawberry/banana flavored liquid. Take missed dose as soon as possible, but do not double dose.

Wholesale cost: $4,615/yr., $384/month

Patient assistance number: 1 (800) 513–3028,
www.gsk.com

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

Potential side effects:

Hypersensitivity (allergic reaction) can be fatal. People experiencing hypersensitivity must stop taking Ziagen and cannot take it again (called “rechallenging”), because of life-threatening, and in at least three cases, fatal reaction. Hypersensitivity usually occurs within six weeks of starting therapy, gets progressively worse and resolves quickly after permanent discontinuation. Approximately 5% of people taking Ziagen experienced hypersensitivity during clinical trials. The primary symptom is low-grade fever with multi-organ symptoms: muscle ache, nausea, vomiting or other gastrointestinal upset (including abdominal pain), malaise (run-down feeling, as with the blahs, fatigue or a flu), respiratory symptoms (cough, difficulty breathing and sore throat) and possibly mild rash. Hypersensitivity might be confused with flu during flu season. The manufacturer recommends that people with symptoms of acute respiratory disease consider hypersensitivity even if other diagnosis such as pneumonia, bronchitis or flu is possible. If hypersensitivity is suspected, stop therapy and contact your doctor immediately. There should be no problem with this if you miss your doses for a few days and did not have an allergic reaction. Black box warning strengthened last year when hypersensitivity wasn’t recognized and people went back on Ziagen, becoming seriously ill.

Other potential side effects include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, anorexia (loss of appetite), high blood sugar and high triglyceride levels (fat in the blood). Rare but potentially fatal toxicity with all NRTIs: pancreatitis (signs include nausea, vomiting, and abdominal pain that often spreads to the chest and back); lactic acidosis (seen mostly in women, especially obese women; greater risk for people with underlying liver disease; signs include deep muscle fatigue, especially in legs, and difficulty breathing); and enlarged, fatty liver (called hepatomegaly with steatosis; check for tenderness below ribs on right side).

Potential drug interactions:

Alcohol increases Ziagen levels and might increase its side effects. The interaction between Ziagen and ethanol was studied in 24 HIV-positive men. No clinically significant interaction was observed. Females have not been studied.

Tips:

Ziagen has the potential to cross the blood-brain barrier, which may prevent or treat neurological damage (such as dementia).

Manufacturer

Ziagen (abacavir sulfate) is a one-tablet, twice daily nucleoside analogue reverse transcriptase inhibitor that is used in combination with other antiretrovirals. Results of one study suggest similar antiviral effects-at 48 weeks-of Ziagen + Combivir and Crixivan + Combivir on the proportion of patients with viral loads below 400 copies/ml. The most serious adverse event is a hypersensitivity reaction in approximately 5 percent of patients, generally characterized by signs and symptoms which include fever, skin rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, cough, shortness of breath, or sore throat. Patients experiencing these symptoms must contact a physician immediately and suspend taking Ziagen. Ziagen and Trizivir should not be started again after a hypersensitivity reaction because you may experience life-threatening symptoms that may include lowering of your blood pressure or death.

—GlaxoSmithKline

Doctor

FDA approved 12/17/98 to treat HIV-1 in adults and children. Abacavir is a prodrug that is pharmacologically active only after conversion to carbovir triphosphate. Abacavir differs from other NRTIs in that it is a carbocyclic nucleoside rather than a dideoxynucleoside. Cross-resistance between abacavir and other NRTIs has been reported. Abacavir increases plasma concentrations of amprenavir (dosage adjustment not required). At 48 weeks, ABC/3TC and amprenavir (twice daily), showed to be potent and well-tolerated in therapy-naïve subjects. Abacavir is generally well tolerated. Potentially life threatening hypersensitivity reactions (usually within the first 6 weeks of treatment) have been reported in 5% of clinical trial patients in combination with lamivudine and zidovudine. Resolves within 2 days after discontinuation. Do not rechallenge. Lactic acidosis, hepatomegaly with steatosis and pancreatitis have also been reported.

—Carlos H. Zambrano, M.D.

Activist

Ziagen (abacavir) is one of the newest nucleosides approved. Head-to-head studies have not been done with other nukes. The DHHS guidelines do not recommend Ziagen as a first line therapy but the drug may be easier to take and less toxic than older drugs and be just as effective.

A serious life-threatening problem with abacavir is seen in approximately 5% of patients. It can cause a hypersensitivity reaction that can be life threatening. If the reaction occurs upon initial use, the drug should be discontinued. Restarting the drug can cause fatal symptoms of hypersensitivity. There was great hope in abacavir for the heavily treated patient. Activists initiated a boycott of Glaxo’s Zantac to pressure them to provide Ziagen early in expanded access. The boycott forced an access program only to find the drug was not as good as activists had hoped.

—Matt Sharp