General Information

Combivir is a combination of 2 nucleoside analogue reverse transcriptase inhibitors, lamivudine and zidovudine.

Combivir is specifically indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Combivir is supplied as tablets for oral administration. 

• Adults and Adolescents weighing greater than or equal to 30 kg: 1 tablet orally twice daily.
• Pediatrics weighing greater than or equal to 30 kg: 1 tablet orally twice daily.

Because Combivir is a fixed-dose tablet and cannot be dose adjusted, Combivir is not recommended in patients requiring dosage adjustment or with hepatic impairment or experiencing dose-limiting adverse reactions.

Mechanism of Action

Lamivudine: Lamivudine is a synthetic nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue.

Zidovudine: Zidovudine is a synthetic nucleoside analogue. Intracellularly, zidovudine is phosphorylated to its active 5-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue.

Side Effects

Adverse effects associated with the use of Combivir may include, but are not limited to, the following:

headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough

The Combivir drug label comes with the following Black Box Warning: Hematologic toxicity, including neutropenia and anemia, has been associated with the use of zidovudine, a component of Combivir. Symptomatic myopathy associated with prolonged use of zidovudine. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues including lamivudine and zidovudine (components of Combivir). Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine, a component of Combivir. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment.

Clinical Trials Data

One Combivir tablet given twice daily is an alternative regimen to EPIVIR tablets 150 mg twice daily plus RETROVIR 600 mg per day in divided doses.

Adults:

The NUCB3007 (CAESAR) trial was conducted using EPIVIR 150-mg tablets (150 mg twice daily) and RETROVIR 100-mg capsules (2 x 100 mg 3 times daily). CAESAR was a multi-center, double-blind, placebo-controlled trial comparing continued current therapy (zidovudine alone [62% of subjects] or zidovudine with didanosine or zalcitabine [38% of subjects]) to the addition of EPIVIR or EPIVIR plus an investigational non-nucleoside reverse transcriptase inhibitor, randomized 1:2:1. A total of 1,816 HIV-1-infected adults with 25 to 250 (median 122) CD4 cells per mm3 at baseline were enrolled: median age was 36 years, 87% were male, 84% were nucleoside-experienced, and 16% were therapy-naive. The median duration on trial was 12 months. The endpoint was HIV-1 progression or death. Current therapy (n=460): 90 (19.6%). EPIVIR plus Current Therapy (n = 896): 86 (9.6%). EPIVIR plus a NNRTIa plus Current Therapy (n = 460): 41 (8.9%).