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. It is available by prescription only and is not indicated for pediatric patients. Severe hypersensitivity warnings have been posted. Please note these warnings and notify a physician immediately if signs occur.

Clinical Results

For more information regarding studies done on the bioequivalence of Trizivir and on numerous trials involving the three components: abacavir sulfate, lamivudine and zidovudine, go to Glaxo Wellcome and look under Clinical Pharmacology and Description of Clinical Studies.

Side Effects

No adverse side effects were seen in pregnant women taking zidovudine, however no data has been collected on the effects of abacavir sulfate and lamovudine on pregnant women. As always, pregnant mothers should consult their physicians carefully before using Trizivir.

Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to Trizivir or other antiretroviral agents, and antiretroviral pregnancy registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV infection.Zidovudine is excreted in breast milk and abacavir has been found in the milk of lactating rats. No data has been collected on lamivudine. Mothers should be instructed not to breastfeed if they are using Trizivir.

Extensive hypersensitivity warnings have been posted concerning the three components of Trizivir. If any hypersensitivity reactions occur discontinue drug use immediately and consult your physician. Severe and fatal reactions could be possible if use of Trizivir is continued after a hypersensitivity reaction is observed. In clinical trials approximately 5% of patients receiving abacavir developed hypersensitivity reactions.

Frequently seen hypersensitivity reaction include, but are not limited to:

• fever
• skin rash
• fatigue
• nausea
• vomiting
• diarrhea
• abdominal pain
• loss of appetite/anorexia
• insomnia and sleep disorders
• chills
• dizziness
• depressive disorders
• cough
• nasal signs and symptoms
• musculoskeletal pain

To facilitate reporting of hypersensitivity reactions and collection of information on each case, an abacavir hypersensitivity registry has been established. Physicians should register their patients by calling 1-800-270-0425.

To see a more complete listing of the warnings and reactions associated with the use of Trizivir please go to: Glaxo Wellcome

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. (From FDA Label)