Trizivir

Nucleoside Reverse Transcriptase Inhibitor

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/abacavir, 150 mg Epivir/3TC/lamivudine, and 300 mg Retrovir/zidovudine/AZT), twice 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: $1,492.49 / month

Manufacturer contact: GlaxoSmithKline,
www.treathiv.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 Trizivir are the same as those of the drugs it contains -- Epivir, Retrovir (zidovudine, AZT), and Ziagen. See those pages for more information. 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. 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, 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 Ziagen. 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. Check with your doctor if you have any side effects after taking this medicine -- don't just stop! 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 Trizivir -- Epivir, Retrovir (zidovudine, AZT), and Ziagen, for more information. Do not take Retrovir (zidovudine, AZT), 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, Mycobutin (rifabutin), 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, when there are concerns about certain toxicities or drug interactions. Procrit or Epogen warning: if hemoglobin target is above manufacturer's recommendation (12 g/dL), the risk for serious and life-threatening cardiovascular complications significantly increases. For patients on Retrovir, which is one of the drugs in Trizivir, measure hemoglobin once a week after starting the anemia drugs until hemoglobin has stabilized. Notify health care provider if experiencing pain and/or swelling in the legs, worsening in shortness of breath, increases in blood pressure, dizziness or loss of consciousness, extreme tiredness, or blood clots in hemodialysis vascular access ports. 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. It soon became apparent that another drug had to be added to this combination to improve efficacy. In our clinic, Trizivir as stand-alone therapy continues in the few patients who have taken it for a long period of time, have a healthy immune system, controlled viral load, and refuse to change the regimen. It is important to remember which antiretroviral components make up Trizivir. In kidney or liver failure, the components may have to be dose adjusted. This will necessitate giving each antiretroviral component separately in the appropriate dose. -- Frank M. Graziano, M.D., Ph.D.

Activist

The maverick of triple-combination therapy, Trizivir was the first drug to combine three drugs (AZT, 3TC, and abacavir) into a single, once-a-day pill. All three components target the reverse transcription stage of the HIV lifecycle, and studies have shown that if used alone, drug resistance can develop rather quickly in some people. And because the whole is only as good as the sum of its parts, due consideration must be given to AZT toxicities and potential Ziagen adverse events. Frankly, Trizivir just isn't as long-lasting, as strong, or as effective as Atripla. Trizivir by itself "is generally not recommended and should only be used when a preferred or an alternative NNRTI-based or PI-based regimen is less desirable because of concerns about toxicities, drug interactions, or regimen complexity." (DHHS Guidelines, November 3, 2008). It bears repeating the lesson learned from Combivir: Know what you're taking! -- Morris Jackson

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