March/April 2009
Combo Drug
Common Name: abacavir sulfate and lamivudine
Brand Name: Epzicom
Class: fixed dose combination -- nucleoside analogs (also called nucleoside reverse transcriptase inhibitors, NRTIs or nukes)
Standard dose: One tablet (600 mg Ziagen/abacavir sulfate and 300 mg Epivir /3TC/ lamivudine), once a day, no food restrictions (may be taken with or without food). Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $996.03 / month
Manufacturer contact: GlaxoSmithKline,
www.epzicom.com, 1 (888) 825-5249
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: The most common side effects of Epzicom are the same as the drugs contained in Epzicom -- Epivir and Ziagen. See those pages for more information. Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on abacavir (Ziagen); see Ziagen. If treatment is stopped because of this serious reaction, you can never take Ziagen, Trizivir, or Epzicom 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, severe nausea, vomiting or abdominal pain, severe tiredness, respiratory symptoms (cough, difficulty breathing and sore throat), and possibly mild rash. These symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should always keep the warning card with you. Hypersensitivity might be confused with flu during flu season, but remember that HSR worsens with every dose. A blood test for HLA-B*5701 can identify people at high risk for this reaction. See tips. There have been studies showing that medications containing abacavir increase the risk of cardiovascular events, including heart attacks and strokes. This applies to people with greater risk factors, (such as smoking, diabetes, and high blood pressure), and is reversible upon discontinuation.
Potential drug interactions: See also the drugs contained in Epzicom, Epivir and Ziagen, for more information. Do not take Combivir, Epivir, Trizivir, Ziagen, Emtriva, Truvada, or Atripla while taking Epzicom, since all or part of these medications are already in Epzicom or have equivalent medications.
Tips: Remember, Epzicom is two drugs in one pill, so see the pages for those drugs, Epivir and Ziagen. Ziagen by itself is FDA approved for either once a day or twice a day dosing. The once-daily formula in Epzicom was found to have the same amount of Ziagen in the blood over 24 hours (bioequivalency) as Ziagen twice a day. As of last year, U.S. HIV treatment guidelines recommend Truvada as the only preferred medication for the NRTI component of a treatment regimen. Epzicom was briefly on the preferred list when a simple and inexpensive test helped to greatly decrease the potential for HSR. But Epzicom was on a roller coaster, and it came back down when studies found that Ziagen was associated with increased cardiovascular disease in people already at high risk for it. Last year, the guidelines added the statement, "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." Truvada, however, is associated with kidney toxicity, although that hasn't been a big problem to date. The Ziagen in Epzicom unfortunately has a hypersensitivity reaction (HSR) in about 8% of people taking it. Inexpensive screening, however, can now virtually eliminate HSR! 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 the potential for this reaction. If HSR is suspected or cannot be ruled out, abacavir products should be discontinued. New drug label change last year states that persons who had a previous suspected HSR may try abacavir again but only if they test negative on the HLA test. The test should never be used to diagnose HSR. The incidence of HSR was the same between Epzicom and Ziagen twice daily (8% vs. 9%), but the incidence of severe reactions was higher with Epzicom (5% vs. 2%). Remember that the HSR cited may have been suspected, not definitely diagnosed. Check with your doctor if you have any side effects after taking this medicine -- don't just stop! Please see package insert for more complete potential side effects and interactions.
Doctor
Epzicom (fixed dose 3TC/abacavir) was approved for once-daily dosing in the treatment of HIV in 2004. This fixed dose combination is well tolerated, has no food restrictions, and plays a significant role in HAART simplification. One must remember that Epzicom contains abacavir and this combination should not be given to an individual who has had an abacavir hypersensitivity reaction (HSR -- see Ziagen). An HLA-B*5701 gene test should be done prior to use of Epzicom in an individual who has never had the drug. If an individual has significant kidney and/or liver problems, fixed dose Epzicom is contraindicated. The reason -- 3TC must be dose adjusted for kidney failure (abacavir is not) and abacavir must be dose adjusted for significant liver failure (3TC is not). To continue therapy with the components of Epzicom in this situation, the drugs should be given separately and dose adjusted as appropriate. You should be aware that there is data that demonstrates Epzicom performed poorly when compared to Truvada (ACTG 5202 study) in individuals with viral loads of greater than 100,000 copies/ml. At the 2008 ICAAC conference, Epzicom was found to perform better than Truvada in those with viral loads less than 100,000 copies/ml (HEAT study). Personally, I find the data confusing and will continue to use Epzicom in my patients until more substantial information is obtained. -- Frank M. Graziano, M.D., Ph.D.
Activist
Because of the inherent risks associated with its Ziagen component (see Ziagen/abacavir), Epzicom was downgraded from a "preferred" to an "alternative" dual-NRTI in the November 2008 update of the DHHS Guidelines. There really isn't much else to say except talk with your medical provider to see if this is a good drug for you, especially if you develop a rash or think you may be at increased risk for a heart attack (again, see Ziagen/abacavir). -- Morris Jackson