General Information

Epivir (lamivudine) is an antiretroviral (anti-HIV) agent, which belongs to a class of drugs called nucleoside analogue reverse transcriptase inhibitors.

Epivir is specifically indicated for use in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients 3 months of age and older.

Epivir is supplied as tablets and as an oral solution for oral administration. The recommended dosing regimen is as follows:

Adult Patients

The recommended dosage of Epivir in HIV-1–infected adults is 300 mg daily, administered as either 150 mg taken orally twice daily or 300 mg taken orally once daily with or without food. If lamivudine is administered to a patient infected with HIV-1 and HBV, the dosage indicated for HIV-1 therapy should be used as part of an appropriate combination regimen.

Pediatric Patients

• Tablets: Epivir scored tablet is the preferred formulation for HIV-1–infected pediatric patients who weigh at least 14 kg and for whom a solid dosage form is appropriate. Before prescribing Epivir scored tablets, pediatric patients should be assessed for the ability to swallow tablets. Epivir can be administered either once or twice daily. The recommended oral dosage of Epivir tablets for HIV-1–infected pediatric patients is calculated on body weight (kg) and should not exceed 300 mg daily. See drug prescription label for weight-based dosing. 
• Oral Solution: The recommended dosage of Epivir oral solution in HIV-1–infected pediatric patients aged 3 months and older is 5 mg per kg taken orally twice daily or 10 mg per kg taken orally once daily (up to a maximum of 300 mg daily), administered in combination with other antiretroviral agents. Consider HIV-1 viral load and CD4+ cell count/percentage when selecting the dosing interval for patients initiating treatment with oral solution.

Mechanism of Action

Epivir (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 HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue.

Side Effects

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

Adults:

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

Pediatrics

• fever
• cough

The Epivir drug label comes with the following Black Box Warning: 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 Epivir. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. Patients with HIV-1 infection should receive only dosage forms of Epivir appropriate for treatment of HIV-1.

Clinical Trial Results

Adults

NUCB3007 (CAESAR) was a multicenter, double-blind, placebo-controlled trial whereby eligible patients receiving zidovudine monotherapy or zidovudine plus zalcitabine or didanosine combination therapy were assigned 52 weeks of treatment with the addition of placebo, lamivudine (150 mg twice a day), or lamivudine (150 mg twice a day) plus loviride (100 mg three times a day). Patients were unaware of type of treatment allocated. The primary endpoint was progression to a new protocol-defined AIDS event or death. The trial randomized a total of 1,816 HIV-1–infected adults with 25 to 250 CD4+ cells per mm3 (median = 122 cells per mm3 ). The median duration on trial was 12 months. The primary endpoint was HIV-1 progression or death. Current Therapy: 90 (19.6%); Epivir plus Current Therapy: 86 (9.6%); Epivir plus an NNRTI plus Current Therapy: 41 (8.9%). In the final analysis of 1,840 patients, progression had occurred in 95 (20%) of 471 placebo-treated patients, 86 (9%) of 907 lamivudine-treated patients, and 42 (9%) of 462 patients who received lamivudine plus loviride.

Pediatrics:

ACTG300 was a multicenter, randomized, double-blind trial that provided for comparison of Epivir plus Retrovir (zidovudine) with didanosine monotherapy. A total of 471 symptomatic, HIV-1–infected therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects were enrolled in these 2 treatment arms. The median age was 2.7 years (range: 6 weeks to 14 years). Results showed a statistically significant difference in time to disease progression in favor of lamivudine in combination with ZDV as compared to ddI alone for children less than 3 years old but not in the older group. This represents a relative reduction in the risk of disease progression of 76% for this strata group. ) Results also showed a significant reduction of viral load and a significant increase of CD4 cell counts in the ZDV/lamivudine arm compared to ddI group except at week 48 for both age strata.