Combivir

Combo Drug

Common Name: zidovudine (AZT) and lamivudine (3TC)

Brand Name: Combivir

Class: fixed dose combination -- nucleoside analogs (also called nucleoside reverse transcriptase inhibitors, NRTIs or nukes)

Standard dose: One tablet (150 mg Epivir/3TC/lamivudine, 300 mg Retrovir/AZT/zidovudine), twice a day (12 hours apart), 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: $937.66 / month

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

Potential side effects and toxicity: Also see drug pages for Epivir (lamivudine, 3TC) and Retrovir (zidovudine, AZT) for more details. Myopathy (muscle damage), flare-up of hepatitis B upon stopping (due to the withdrawal of Epivir, which is contained in Combivir) and hematologic (blood-related) toxicity including anemia and neutropenia. May be taken with food to decrease potential nausea associated with AZT. 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.

Potential drug interactions: See the drugs contained in Combivir -- Epivir (lamivudine, 3TC), and Retrovir (zidovudine, AZT). Do not take zidovudine (Retrovir), Epivir, Epivir-HBV, Epzicom, Trizivir, Emtriva, Truvada, stavudine (Zerit), or Atripla while taking Combivir, since all or part of these medications are already in Combivir or have equivalent medications.

Tips: Combivir is the combination of lamivudine, 3TC (Epivir) and zidovudine, AZT (Retrovir) into one pill; see the pages of those individual drugs for more information. Combivir has been shown in multiple clinical trials to be a potent regimen with either a protease inhibitor or an NNRTI. The zidovudine (AZT) in Combivir can cause fatigue and anemia. One head-to-head study against Truvada found greater toxicity with Combivir, due to anemia (see Retrovir). The warning on the anemia drugs Procrit and Epogen has not been linked to patients with HIV, although clinical data do not rule out a possible increased risk for cardiovascular events. The zidovudine/AZT in Combivir is associated with lipoatrophy (fat loss of the arms, legs, face, and/or buttocks -- sometimes called "AZT butt"). The lipoatrophy could be irreversible or take a long time to rebuild. Please see package insert for more complete potential side effects and interactions.

Doctor

Combivir (combination AZT/3TC) was the first fixed dose combination antiretroviral therapy approved (1997) for HIV infection. By simplifying taking two tablets twice a day into just one tablet twice a day, it became one of the first demonstrations of the importance and enthusiasm for "fixed combinations." As a result, it became widely used in combination with other antivirals at the time. However, there were several limitations that also became apparent over time. One was that it could not be successfully used when taken once daily, due to the short amount of time enough AZT would stay in the cells -- not enough when it was dosed just once daily. Second was that AZT was increasingly associated with both initial and longer term side effects that were not shared by other treatment options. For example, fat loss, or "lipoatrophy" is more common when taking AZT when compared to what was seen when taking either abacavir or tenofovir, though AZT was at least better than d4T (Zerit) on this side effect. In addition, some data suggest that the lipoatrophy associated with three or more years of taking AZT is difficult to reverse even after switching to other safer antivirals. Thus, the popularity of this combination has declined and it is considered an "alternative" by the DHHS guidelines panel. However, it continues to be listed as "preferred" for women who are pregnant, given the extensive data for this drug in that setting, despite its association with nausea and anemia, both undesirable side effects for anyone, including pregnant women. -- Cal Cohen, M.D.

Activist

The original fixed dose combination that started the craze for combining drugs. Effective and still widely used, it's still the sum of its parts, so suffers from the anemia, fatigue, and lipoatrophy caused by its AZT component. These days there are better options for those who don't want to take their meds twice a day, so it's no longer a preferred medication in the Guidelines. But the positive central nervous system (CNS) penetration profile makes it valuable for those experiencing cognitive difficulties. It's also the recommended backbone in regimens for pregnant women. -- Jeff Taylor