General Information

Trizivir tablets contain three nucleoside analogues; abacavir sulfate (Ziagen), lamivudine (Epivir or 3TC) and zidovudine (Retrovir, ZDV or azidothymidine). This combination therapy has been developed to simplify the dosing regimen for HIV patients.

Trizivir is specifically indicated for use in combination with other antiretrovirals or alone for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.

Trizivir is supplied as oral tablets. The recommended dosage is one tablet taken orally twice daily with or without food.

Mechanism of Action

Abacavir: Abacavir is a carbocyclic synthetic nucleoside analogue. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate. Carbovir triphosphate is an analogue of deoxyguanosine-5-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3 -OH group in the incorporated nucleoside analogue prevents the formation of the 5 to 3 phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

Lamivudine: Lamivudine is a synthetic nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5-triphosphate metabolite, lamivudine triphosphate (L-TP). The principal mode of action of L-TP is inhibition of RT via DNA chain termination after incorporation of the nucleoside analogue. L-TP is a weak inhibitor of mammalian DNA polymerases-a and -B and mitochondrial DNA polymerase-y.

Zidovudine: Zidovudine is a synthetic nucleoside analogue. Intracellularly, zidovudine is phosphorylated to its active 5-triphosphate, zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of RT via DNA chain termination after incorporation of the nucleoside analogue. ZDV-TP is a weak inhibitor of the mammalian DNA polymerase-a and mitochondrial DNA polymerase-y and has been reported to be incorporated into the DNA of cells in culture. 

Side Effects

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

• nausea
• headache
• malaise and fatigue
• nausea and vomiting

The Trizivir drug label comes with the following Black Box Warning:

Hypersensitivity Reactions

• Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing products.
• Hypersensitivity to abacavir is a multi-organ clinical syndrome.
• Patients who carry the HLA-B*5701 allele are at a higher risk of experiencing a hypersensitivity reaction to abacavir.
• Trizivir is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients.
• Discontinue Trizivir as soon as a hypersensitivity reaction is suspected. Regardless of HLA-B*5701 status, permanently discontinue Trizivir if hypersensitivity cannot be ruled out, even when other diagnoses are possible.
• Following a hypersensitivity reaction to Trizivir, NEVER restart Trizivir or any other abacavir-containing product.

Hematologic Toxicity

• Hematologic toxicity, including neutropenia and anemia, has been associated with the use of zidovudine, a component of Trizivir.

Myopathy

• Symptomatic myopathy associated with prolonged use of zidovudine.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including abacavir, lamivudine, and zidovudine (components of Trizivir). Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Exacerbations of Hepatitis B

• 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 Trizivir. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment.

Clinical Trial Results

FDA approval was based on clinical trials of the individual components of Trizivir.