POSITIVELY AWARE MARCH/APRIL 2011
brand name: Ziagen
common name: abacavir sulfate
class: Nucleoside analog reverse transcriptase inhibitor
(nucleoside analog, NRTI, or nuke)
manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872
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). Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Dose does not need to be adjusted for people with kidney impairment.
AWP: $615.38 / month, $161.78 for 240 ml solution (20 mg/ml)
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 now identify patients at high risk for this reaction and virtually eliminate HSR. If treatment is stopped because of this serious reaction, you can never take Ziagen or any other product containing abacavir, such as Epzicom or Trizivir again (called “re-challenging”). Rechallenging 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). About 90% of HSR occurs within the first six weeks of treatment. 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 sudden 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), and that the risk is reversible upon discontinuation. Studies looking into this possible association had mixed results. One explanation for the unexpected link was a finding that people with kidney problems were put on Ziagen in order to avoid medications containing Viread, which have the potential for kidney toxicity. These individuals already have a strong risk for cardiovascular disease. The available data regarding cardiovascular risk with abacavir remain inconclusive. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged liver.
Potential drug interactions
Do not take with Epzicom or Trizivir, since Ziagen is already in these medications. Excessive alcohol increases Ziagen 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. Avoid Ziagen in people with moderate/severe liver disease. 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 (abacavir 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, MD, MPH
Activist’s comments
Once a popular once-daily drug, Ziagen has had a couple of setbacks. A potentially fatal hypersensitivity reaction (usually starting as a severe rash) can now be avoided by a genetic test to rule out people predisposed to it. The second was the finding of several large trials that those on Ziagen had an increased risk of cardiovascular events. Further studies yielded conflicting results, so it’s still unclear whether, or to what degree, Ziagen might cause cardiovascular disease. Consequently, cautious doctors and patients with other risk factors for heart disease (those who smoke, have high blood pressure or a family history of heart disease, etc.) have been avoiding it until further research can answer the question. —Jeff Taylor
