Abacavir + Lamivudine + Zidovudine

Indications

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

Pharmacology

Abacavir is a carbocyclic synthetic nucleoside analogue and an antiviral agent. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, 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. Viral DNA growth is terminated because the incorporated nucleotide lacks a 3'-OH group, which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation.

Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination.

Zidovudine, a structural analog of thymidine, is a prodrug that must be phosphorylated to its active 5′-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. It competes with the natural substrate dGTP and incorporates itself into viral DNA. It is also a weak inhibitor of cellular DNA polymerase α and γ.

Dosage & Administration

Recommended dosage for adults and pediatric patients weighing at least 40 kg: The recommended dosage is one tablet taken orally twice daily with or without food.

Due to fixed-dose tablet and cannot be dose adjusted, this is not recommended for:
  • Pediatric patients who weigh less than 40 kg.
  • Patients with creatinine clearance less than 50 ml/minute
  • Patients with mild hepatic impairment.

Interaction

Abacavir: In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg twice daily (twice the currently recommended dose), oral methadone clearance increased. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.

Lamivudine: Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines

Zidovudine: Concomitant use of zidovudine with the following drugs should be avoided since an antagonistic relationship has been demonstrated in vitro: Stavudine, Doxorubicin, Nucleoside analogues, e.g., ribavirin

Contraindications

This is contraindicated in patients:
  • Who have the HLA-B*5701 allele
  • With prior hypersensitivity reaction to abacavir, lamivudine, or zidovudine.
  • With moderate or severe hepatic impairment.

Side Effects

The most commonly reported adverse reactions (incidence at least 10%) in clinical trials were nausea, headache, malaise and fatigue, and nausea and vomiting.

Pregnancy & Lactation

Pregnancy Category C. There are no adequate and well-controlled studies of this preparation in pregnant women. This drug should be used during pregnancy only if the potential benefits outweigh the risks. Women infected with HIV should be instructed not to breastfeed due to potential for HIV transmission.

Precautions & Warnings

Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of this preparation. These hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during. Patients who carry the HLA-B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA-B*5701 allele have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA-B*5701 screening was not performed. The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA-B*5701 allele were excluded. In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making.

Overdose Effects

There is no known specific treatment for overdose with this preparation. If overdose occurs, the patient should be monitored and standard supportive treatment applied as required.

Therapeutic Class

Drugs for HIV / Anti-retroviral drugs

Storage Conditions

Store at a dry and cool place. Protect from light and moisture. Keep the medicine out of the reach of children.

Available Brand Names