Brand name: Ziagen

Generic name: abacavir sulfate (abacavir), or ABC

Class: Nucleotide reverse transcriptase inhibitor(nucleotide, NtRTI, or nuke)

Manufacturer: ViiV Healthcare, www.viivhealthcare.com, (877) 844-8872

AWP: $670.37/month, $161.78 for 240 mL solution (20 mg/mL)

Standard Dose: Two 300 mg tablets once a day (or one 300 mg tablet twice a day), with or without food, with no dietary restrictions; scored tablets available for children. A strawberry/banana flavored liquid is available (20 mg/mL). Ziagen (abacavir) can be used in children as young as 3 months old. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose does not need to be adjusted for people with kidney impairment.

Potential side effects and toxicity: Approximately 5-8% of people who took abacavir experienced hypersensitivity reaction (HSR, an allergic-like reaction). A simple and inexpensive blood test for HLA-B*5701 (a genetic marker) can identify patients at risk for this reaction and virtually eliminate HSR. If the HLA-*B5701 test is positive, this means that you will likely have the HSR if you start taking abacavir, and an allergy to it should be entered in your medical record even if you have never taken abacavir in the past. If you start abacavir without having the HLA-B*5701 test done, you should be monitored closely the first 6 weeks or so (HSR occurs usually within the first 6 weeks). If you develop the HSR reaction, treatment with abacavir will be stopped and you can never take abacavir or any other product containing abacavir, such as Epzicom or Trizivir, again (called "re-challenging"). Re-challenging can cause a rare life-threatening reaction. (This does not apply to missed doses when there's no HSR, but watch for symptoms if you've stopped the drug for at least a few days). Symptoms of HSR usually worsen, very slowly, with every dose. People who think they are experiencing HSR must be evaluated by an experienced HIV provider right away before they stop taking abacavir. Symptoms resolve quickly (24-48 hours) after permanent discontinuation. Symptoms usually, but not always, include some combination of fever; muscle ache; malaise (general ill feeling); severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, and sore throat); and possible rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. HSR might be confused with flu during flu season, but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine -- don't just stop! See "More information." More common side effects may include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, trouble sleeping, unusual dreams, and anorexia (loss of appetite). Some observational studies seemed to indicate that abacavir may increase the risk of cardiovascular events, including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, and drug use). One possible explanation was found -- people with kidney problems were put on abacavir in order to avoid Viread (tenofovir), which has potential for kidney toxicity and those people already had a strong risk for heart problems. The FDA conducted an analysis of 26 randomized clinical trials that evaluated abacavir. This analysis did not show an increased risk of heart attacks associated with the use of abacavir. Last year, DHHS HIV treatment guidelines added the statement, "to date, no consensus has been reached either on the association of [abacavir] use with MI [myocardial infarction, or heart attack] risk or a possible mechanism for the association." People who have high risk for heart disease are monitored more closely and the decision to stop or never start a regimen containing abacavir is up to you and your provider. See chart for potential drug class side effects.

Potential drug interactions: Do not take with Epzicom or Trizivir, since abacavir is already in these medications. Excessive alcohol increases abacavir levels and may increase side effects.

More information: The manufacturer recommends that people with symptoms of acute respiratory disease consider HSR even if another diagnosis such as pneumonia, bronchitis, or flu is possible. Do not use a skin patch test to confirm HSR. Dose adjustment is needed in people with mild liver disease and the oral solution will need to be used in these patients. There are no data in people with moderate/severe liver disease and therefore it should not be used in those individuals. See package insert for more complete information on potential side effects and interactions.

Doctor's Comments

Ziagen is a well-tolerated drug that is typically combined with 3TC (see Epzicom), or less commonly with 3TC and AZT (see Trizivir). While it has few side effects, it can cause a potentially dangerous hypersensitivity reaction (HSR) in some people. Fortunately, we now have a blood test, HLA B*5701, that accurately predicts who will develop this reaction and who won't. The test should always be ordered before starting abacavir, and people with a positive test should never take abacavir in any of its forms (Ziagen, Epzicom, or Trizivir). There is controversial evidence linking abacavir with an increased risk of heart attack. This evidence comes from several large observational studies, but the association hasn't been seen in several other large studies, and no one knows what the mechanism of the association would be. Experts disagree on whether abacavir increases cardiac risk or not, but most agree that until we know for sure, it's best to avoid the drug in people with coronary heart disease or multiple risk factors for heart disease. The comparison of Ziagen and Viread for initial therapy is discussed under Epzicom and Truvada.

-- Joel Gallant, M.D., M.P.H.

Activist's Comments

Starting out as a popular once-daily drug, Ziagen has also fallen out of favor. Like so many pop singers and boy bands in the music industry, this drug came out with much fanfare, and ended up in the doghouse. A potentially fatal hypersensitivity reaction was reported, as well as several clinical trials identifying abacavir as possibly increasing the risk of cardiac events for some people. With all of these limitations and potentially dangerous possibilities, this drug is usually passed over for far less worrisome options.

-- Joey Wynn

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