Ziagen
Common Name: abacavir sulfate
Brand Name: Ziagen
Class: nucleoside analogs (also called nucleoside reverse transcriptase inhibitors, NRTIs, or nukes)
Standard dose: Two 300 mg tablets once a day (or one 300 mg tablet twice a day), with or without food, and no food restrictions; new scored tablets available for children. A strawberry/banana flavored liquid is available (20mg/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.
AWP: $581.10 / month, $152.77 for 240 ml bottle
Manufacturer contact: ViiV Healthcare,
www.treathiv.com, 1 (877) 844–8872
Potential side effects and toxicity: Approximately 5-8% of people taking abacavir experienced hypersensitivity reaction (HSR, an allergic-like reaction). A simple and inexpensive blood test for HLA-B*5701 can identify patients at high risk for this reaction and virtually eliminate HSR. 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. If treatment is stopped because of this serious reaction, you can never take Ziagen, Epzicom, or Trizivir again (called “re-challenging”) because of life-threatening and, in a few instances, 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). 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. See tips. More common side effects may include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, 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 is reversible upon discontinuation. Studies looking into this possible association had mixed results (see interview with Dr. Cal Cohen on page 56). One explanation for the unexpected link was a finding that people with kidney problems were put on Ziagen in order to avoid its primary competitor, Viread, which has the potential for kidney toxicity. These individuals already have a strong risk for cardiovascular disease. The available data regarding cardiovascular risk with abacavir remains 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, fatty liver. Symptoms include persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged, fatty liver.
Potential drug interactions: Excessive alcohol increases Ziagen levels and may increase side effects. 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 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. Check with your doctor if you have any side effects after taking this medicine—don’t just stop! Dose adjustment needed in people with moderate liver disease. Avoid Ziagen in people with severe liver disease. 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. It had also achieved favorable use due to studies showing rates of lipoatrophy that were similar to tenofovir, and lower than either AZT or d4T. However, there are a few factors which have to be considered for this drug. One is that abacavir must not be given to an individual who has a positive HLA-B*5701 test, as this test predicts who is likely to experience a “hypersensitivity reaction.” Moreover, restarting abacavir in someone who had the HSR reaction can be fatal, leading to the importance of understanding this syndrome when considering this drug. If an individual has significant liver problems, abacavir is not recommended for use. The most recent studies of Epzicom demonstrate a greater risk of virologic failure versus what is seen with the use of Truvada in those individuals starting treatment with viral loads of greater than 100,000 copies/ml. In addition, there were more side effects reported with this drug versus Truvada in that ACTG study. Recent guideline panels have uniformly commented on the data seen in several, though not all, large studies about an increased risk of cardiovascular disease (heart attacks or an MI) when using an abacavir-containing regimen versus what is seen with most of drugs in this class. Finally, there are data raising a question about the interaction of abacavir and ribavirin, a drug that is currently essential for the treatment of hep C and this has led to some reluctance to use abacavir-containing regimens in someone being treated for hep C. Thus, these concerns—reduced virologic activity as well as additional toxicity issues—have collectively led this agent to be considered primarily for patients in whom Truvada is not considered a better choice. —Cal Cohen, MD
Activist
This once-a-day drug has a couple of strikes against it. The potentially fatal hypersensitivity reaction can now be avoided with a genetic test to screen out those predisposed to have it. However, patients should be vigilant about any possible reactions (like rash) when starting this drug and let their doctor know immediately. The second strike is a little murkier—the potential for higher rates of cardiac disease that have emerged in several large trials. Subsequent research shows conflicting evidence on this, so the jury is still out on whether this drug contributes to heart disease risk or not. Nonetheless, those who already have heart disease, or are at greater risk (those who smoke, have a family history of heart disease, high blood pressure, etc.) might look into other options, if they have them, until a clearer picture emerges on possible cardiac risks of this drug. —Jeff Taylor
