March/April 2009
Common Name: abacavir sulfate (ABC)
Brand Name: Ziagen
Class: nucleoside analog (also called nucleoside reverse transcriptase inhibitor, NRTI, or nuke)
Standard dose: Two 300 mg tablets once a day (or one 300 mg tablet twice a day), no food restrictions (may be taken with or without food); new scored tablets available for children. A strawberry/banana flavored liquid is available. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $571.05 / month, $150.13 for liquid
Manufacturer contact: GlaxoSmithKline,
www.treathiv.com, 1 (888) 825-5249
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: Approximately 8% of people taking abacavir experienced hypersensitivity reaction (HSR, an allergic-like reaction). People who think they are experiencing HSR must be evaluated by an experienced HIV provider as soon as possible before they stop taking abacavir. Be very careful, especially in the first two months of treatment. Symptoms worsen with every dose, but very slowly. If treatment is stopped because of this serious reaction, you can never take abacavir, Epzicom, or Trizivir again (called "re-challenging") because of life-threatening and potentially fatal 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). This reaction usually occurs during the second week of treatment, but may take as long as six weeks to appear, and can occur anytime during treatment. It gets progressively worse and resolves quickly (24-48 hours) after permanent discontinuation. Symptoms usually, but not always, include some combination of sudden fever, muscle ache, severe nausea, vomiting or abdominal pain, severe tiredness, respiratory symptoms (cough, difficulty breathing, and sore throat) and, possibly, mild rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. Always keep the warning card with you. HSR might be confused with flu during flu season, but remember that it worsens with every dose. Check with your doctor if you have any side effects after taking this medicine -- don't just stop! A blood test for HLA-B*5701 can identify patients at high risk for this reaction. New label change states that persons who had a previous suspected HSR may try abacavir again, but only if they test negative on the HLA test. More common side effects may include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, and anorexia (loss of appetite). Studies show that abacavir increases the risk of cardiovascular events, including heart attacks and strokes. This applies to people with greater risk factors (such as smoking), and is reversible upon discontinuation.
Rare but potentially fatal toxicity with all NRTIs: 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 severe in women, people who are obese, and people who have been taking NRTIs for a long time; it is more common in people with liver disease, but can occur in people without a history of liver damage. Symptoms include persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged, fatty liver. Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and blood in the urine. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Stop all HIV medications and see a health care provider right away.
Potential drug interactions: Excessive alcohol increases abacavir levels and may increase side effects. Dose adjustment needed in people with moderate liver disease. Avoid Ziagen in people with severe liver disease. Do not take with Epzicom or Trizivir, since Ziagen is already in these medications.
Tips: The U.S. HIV treatment guidelines now state, "Pending additional data, [Epzicom] should be used with caution in individuals who have plasma HIV RNA [viral load] greater than 100,000 copies/mL, as well as in persons at higher risk for cardiovascular disease." The manufacturer also recommends that people with symptoms of acute respiratory disease consider HSR even if another diagnosis such as pneumonia, bronchitis, or flu is possible. An analysis of 8,000 patients found a reduced risk of HSR in blacks and in men. Please see package insert for more complete potential side effects and interactions.
Doctor
Ziagen (abacavir), first developed as a twice-daily drug, was later approved as a once-daily agent (2004) and in the fixed dose combinations Trizivir (3TC/AZT/abacavir in 2000) and Epzicom (3TC/abacavir in 2004). Abacavir rapidly became an easy to take and popular component of HAART therapy. At first the hypersensitivity reaction (HSR -- potentially fatal), seen in a relatively small number of individuals (~8%), gave pause to those of us prescribing the drug. I can remember the HSR conversation with patients and the wide-eyed look when I said it could be "potentially fatal." The finding that those who have a specific gene (HLA-B*5701) are most susceptible to having the HSR made use of the drug safer. This meant all patients needed a gene test before prescribing abacavir which added cost and time to the antiretroviral decision. My experience with the HSR and HLA-B*5701 gene has been colored somewhat by a patient treated with Ziagen in our clinic. This individual was re-challenged with abacavir after a question of an abacavir HSR but negative HLA-B*5701 gene test. The patient had a severe HSR within an hour of the first re-challenge dose. Subsequent abacavir skin patch testing was found to be negative. While I strongly believe that the gene test has significantly reduced the incidence of HSR with abacavir, I suggest a small number of individuals are still at risk for HSR through a mechanism not associated with the HLA-B*5701 gene. I would advise continued vigilance during the first weeks of abacavir dosing and never restart abacavir after an HSR. A major issue clouding abacavir use is the reported increased risk of myocardial infarction (MI, or heart attack) with current exposure to the drug. This finding was a total surprise to us. Until we get more definitive clinical trial data, I primarily avoid use of the drug in those with documented increased MI risk factors. Personally, I continue to find abacavir alone or in fixed dose combination a valuable part of HAART therapy. -- Frank M. Graziano, M.D., Ph.D.
Activist
As always, really talk with your doctor to be sure you understand any possible side effects before starting a medication. This is especially true with drugs containing abacavir (Ziagen, Epzicom, and Trizivir). If considering starting an abacavir-containing drug, have a HLA-B*5701 test done to screen for abacavir hypersensitivity reaction (HSR). HSR is an allergic reaction to abacavir that usually occurs within the first six weeks of therapy and typically only affects less than 10% of people taking it, but it can be severe and sometimes fatal. Those who test positive for HLA-B*5701 should not take this drug. Another cautionary note: studies also show increased risk for a cardiac event (heart attack) in people taking an abacavir-containing drug, particularly for those with five or more cardiovascular risk factors (smoking, male, obese, high cholesterol, Black/Latino, etc.). Recently FDA-approved for child dosing according to body weight. (Interestingly, the U.S. patent for abacavir expires in December 2009.) -- Morris Jackson