Epzicom

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/ABC and 300 mg Epivir /lamivudine/3TC), once a day, with or without food, and no food restrictions. 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: $1,013.56 / month

Manufacturer contact: ViiV Healthcare, 1 (877) 844-8872

Potential side effects and toxicity: The most common side effects of Epzicom are the same as the drugs it contains -- see Epivir and Ziagen. Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on Ziagen (abacavir); see Ziagen. A simple and inexpensive blood test for HLA-B*5701 can identify people 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. 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; 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. Hypersensitivity might be confused with flu during flu season, but remember that HSR worsens with every dose. 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.

Potential drug interactions: See also the drugs contained in Epzicom, Epivir and Ziagen, for more information. Do not take Combivir, Epivir, Epivir-HBV, 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, Epivir-HBV and Ziagen. Currently, U.S. HIV treatment guidelines recommend Truvada over Epzicom as a preferred agent for the NRTI component of a treatment regimen. Epzicom is listed as an alternative NRTI backbone due to the aforementioned potential cardiac risks. See Ziagen for more details. Also, with publication last year of preliminary results from a study of 2,000 participants, ACTG 5202, Epzicom has lost its battle -- for now -- against its main competitor, Truvada. The study team reported that while both medications reduced viral load, for those people who started treatment with more than 100,000 viral load, Epzicom was "significantly less effective at controlling HIV" in the regimens tested. Moreover, time to a serious adverse event was sooner in the people taking Epzicom. These efficacy and safety findings were not confirmed in a manufacturer-sponsored study, HEAT, another large study (700 participants) comparing Epzicom and Truvada. Still, in HIV therapy, there's always use for an alternative choice of drugs and the DHHS guidelines 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. However, [Epzicom] remains a good alternative dual-NRTI option for some treatment-naive patients." Remember, too, that Truvada has its own side effect and drug interaction issues, although it's famed for its tolerability. Ziagen by itself is FDA approved for either once-daily or twice-daily dosing. The once-daily formula in Epzicom was found to leave the same amount of Ziagen in the blood over 24 hours (bioequivalency) as Ziagen twice a day. The test should never be used to diagnose HSR. Do not use a skin patch test to confirm HSR. 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. Check with your doctor if you have any side effects after taking this medicine -- don't just stop! The incidence of HSR was the same between Epzicom once-daily 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. 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 usually well tolerated, and has no food restrictions. While there was initial enthusiasm and study of this drug, both for initiating treatment and for simplification for patients already on suppressive treatment, there are a few factors that have limited its use and contribute to why this combination is no longer considered "preferred" by the 2009 DHHS guidelines. It is also critical to recall that since Epzicom contains abacavir, this combination must not be given to an individual who has had an abacavir hypersensitivity reaction (HSR -- see Ziagen). An HLA-B*5701 genetic test should be done prior to use of Epzicom in an individual who has never had the drug abacavir as this test does an excellent job of predicting likelihood of the HSR reaction. If an individual has significant kidney and/or liver problems, fixed dose Epzicom is not recommended for use. The most recent studies of Epzicom demonstrated 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. Recently, guideline panels have commented on data seen in several, but not all, studies about an increased risk of cardiovascular disease -- specifically heart attacks, when using an abacavir-containing regimen as compared to what is seen when patients are on most other nucleosides. 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. Collectively, these concerns -- reduced virologic activity, additional toxicity issues, and drug interactions -- have led this agent to be considered primarily for patients in whom Truvada is not considered reasonable for whatever reason. -- Cal Cohen, M.D.

Activist

This convenient once-a-day pill was once considered a major improvement over Combivir. The abacavir in Epzicom, with its potential for hypersensitivity, and now, possible cardiac risks (see Ziagen), makes Epzicom less popular than it once was now that there are other options available. -- Jeff Taylor