abacavir sulfate (ABC)
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). A strawberry/banana flavored liquid is available. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $519.92 / month
Manufacturer contact: GlaxoSmithKline,
www.treathiv.com, 1 (888) 825–5249
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) during clinical trials. 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, they 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, but 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. See Epzicom tips. 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. More common side effects include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, and anorexia (loss of appetite). Rare but potentially fatal toxicity with all NRTIs is hepatomegaly (enlarged liver) with steatosis 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 nukes for a long time; and 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, and difficulty breathing or shortness of breath; and enlarged, fatty liver (called hepatomegaly with steatosis).
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: This is a potent NRTI, but due to the potential hypersensitivity reaction (HSR) U.S. HIV treatment guidelines do not recommend Ziagen as first-line treatment. Inexpensive screening, however, can now virtually eliminate the risk of HSR! Healthcare providers should visit www.hlab5701survey.com to learn more and get free tests. Don’t be afraid of genetic testing—it’s only looking for one tiny part of your genes. Regardless of the results, it is important to monitor for the potential for this reaction. If HSR is suspected or cannot be ruled out, abacavir products should be discontinued. The test should never be used to diagnose HSR. It is important to remember that HSR occurs in 5–8% of people and is not fatal unless ignored, and to communicate any and all symptoms to your healthcare provider. Do not stop Ziagen until you have discussed this with your healthcare provider. You don’t want to burn through a potent and tolerable HIV drug. The manufacturer recommends that people with symptoms of acute respiratory disease consider HSR even if other 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.
Abacavir has always been a great nuke—potent, easy, and well tolerated—but it’s also been a pain in the ass. A small fraction of people who took it developed the abacavir hypersensitivity reaction (HSR), a flu-like reaction that got steadily worse and that could even be fatal in people who developed HSR, stopped the drug, and then took it again. When I prescribed the drug, I had to spend about five minutes talking to patients about HSR, and then another 10 minutes on the phone the next day, trying to convince them to take it after they read about the “RISK OF DEATH!” in the card they got from the pharmacist. Things are much better now: You can virtually eliminate the risk of HSR by ordering a HLA-B*5701 blood test first. If it’s positive, don’t take abacavir (in any of its many forms.) If it’s negative, you should still be aware of HSR, but it’s unlikely to happen. Ziagen doesn’t have any known long-term toxicity. The unanswered question is how it compares to Viread. Several head-to-head trials comparing Truvada and Epzicom are in progress.—Joel Gallant, M.D.
Ziagen came through development with high hopes as a more potent and generally less toxic addition to the nucleoside class. Its otherwise good reputation was tarnished though by an occasional problem called hypersensitivity reaction, which is another way of saying a severe allergic reaction. In the worst cases, the reaction could be fatal, and it wasn’t always easy to distinguish the onset of the problem from a simple rash. In the case of Ziagen, rechallenging people was the surest route to a severe or fatal reaction. Over time, most physicians have learned how to recognize and deal with this reaction before it becomes serious. More importantly, there is now a genetic test that a person can take which predicts who will and who will not have the reaction. Even at worst, without pre-testing, the problem is likely to occur in less than 3% of the population. The unfortunate thing is that this largely managed problem hangs like a cloud over the drug and still discourages some doctors and patients from considering it. The truth is that when properly used, Ziagen is a better and safer choice than any of the older nucleoside analogue drugs and offers robust competition to Viread as the top of the field.—Martin Delaney