Trizivir
Combo Drug
Common Name: abacavir sulfate, zidovudine, and lamivudine
Brand Name: Trizivir
Class: fixed dose combination—nucleoside analogs (also called nucleoside reverse transcriptase inhibitors, NRTIs, or nukes)
Standard dose: One tablet (300 mg Ziagen/ABC/abacavir, 150 mg Epivir/3TC/lamivudine, and 300 mg Retrovir/zidovudine/AZT), twice 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: $1,518.76 / month
Manufacturer contact: ViiV Healthcare, 1 (877) 844-8872
Potential side effects and toxicity: The most common side effects of Trizivir are the same as those of the drugs it contains—see Epivir, Retrovir, and Ziagen. Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on 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. Symptoms worsen, very slowly, with every dose. If treatment is stopped because of this serious reaction, 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, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, and sore throat); and possibly 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. See Ziagen and tips below. 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.
Other side effects associated with Trizivir may include headache, nausea, upset stomach, and fatigue. May be taken with food to decrease potential nausea associated with Retrovir.
Potential drug interactions: See also the drugs contained in Trizivir—Epivir, Retrovir (zidovudine, AZT), and Ziagen, for more information. Do not take Retrovir (zidovudine), Epivir, Epivir-HBV, Ziagen, Epzicom, Emtriva, Truvada, or Atripla while taking Trizivir, since all or part of these medications are already in Trizivir or have equivalent medications. If you are taking one of the following medications, consult your doctor or pharmacist before starting Trizivir: Zerit, ribavirin, interferon, rifampin, probenecid, methadone, Cytovene (ganciclovir), Valcyte (valganciclovir), Biaxin (clarithromycin), Daraprim (pyrimethamine), flucytosine, Fungizone (amphotericin B), doxorubicin, and hydroxyurea.
Tips: See the drugs contained in Trizivir: Epivir, Retrovir (zidovudine, AZT), and Ziagen. Trizivir is the only triple combination NRTI that has been studied in a randomized, controlled study, but this has shown it to be inferior to the standard treatment of two NRTIs plus an NNRTI. U.S. treatment guidelines recommend that Trizivir should only be used if other options are not possible due to toxicities or drug interactions associated with other HIV regimens. The zidovudine/AZT in Trizivir is associated with lipoatrophy (fat loss from the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or take a long time to rebuild. The HLA 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! Please see package insert for more complete potential side effects and interactions.
Doctor
Trizivir (AZT/3TC/abacavir) was approved for twice-daily dosing in the treatment of HIV infection in 2000. This was the first fixed dose triple combination antiretroviral to be produced. Initially, Trizivir (alone) was a popular choice because it greatly simplified therapy for HIV. However, it lost favor due to a few concerns. One was that an important randomized trial found that Trizivir was not as virologically active as another three-drug combination containing Combivir and Sustiva. In addition, it has all of the safety concerns associated with the use of AZT and Ziagen which are detailed in those sections. Therefore, these issues, combined with the current availability of several once daily options, have led to Trizivir being listed as “generally not recommended” for initial regimens by the DHHS guidelines committee. —Cal Cohen, MD
Activist
The original three-in-one combo (albeit twice a day), Trizivir enjoyed a brief heyday as the ultimate convenience regimen before studies showed that it just wasn’t as effective or durable as other PI or non-nuke combos, and it has quickly fallen from favor. The AZT and abacavir components come with their own problems as well. It has been quickly eclipsed by Atripla for those who want a convenient one pill, once a day regimen. —Jeff Taylor
