Abacavir + Lamivudine + Zidovudine

Prescribing Information (Research Brand)

Indications

This is indicated alone or in combination with other antiretroviral agents for the treatment of HIV infection.

Therapeutic Class

Drugs for HIV / Anti-retroviral drugs

Pharmacology

Abacavir: Abacavir is a carbocyclic synthetic nucleoside analogue. Intracellularly, Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate. Carbovir triphosphate inhibits the activity of HIV reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Following oral administration, abacavir is rapidly absorbed and extensively distributed. Binding of abacavir to human plasma proteins is approximately 50%. The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase to form the 5’- carboxylic acid and glucuronyl transferase to form the 5’-glucuronide.

Lamivudine: 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. Following oral administration, Lamivudine is rapidly absorbed and extensively distributed. Binding to plasma protein is low.

Zidovudine: 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 nucleoside analogue. Following oral administration, Zidovudine is rapidly absorbed and extensively distributed. Binding to plasma protein is low. Zidovudine is eliminated primarily by hepatic metabolism.

Dosage & Administration

The recommended oral dose for adults and adolescents is 1 tablet twice daily. This drug is not recommended in adults or adolescents who weigh less than 40 kg because it is a fixed-dose tablet.

Interaction

No clinically significant changes to pharmacokinetic parameters were observed for Abacavir, Lamivudine, or Zidovudine when administered together.

Abacavir: Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure.

Lamivudine: Trimethoprim (TMP) 160 mg/sulfamethoxazole (SMX) 800 mg once daily has been shown to increase Lamivudine exposure (AUC). The effect of higher doses of TMP/SMX on Lamivudine pharmacokinetics has not been investigated. Lamivudine and Zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of this combination in combination with zalcitabine is not recommended.

Zidovudine: Coadministration of ganciclovir, interferon-alpha, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine. Concomitant use of zidovudine with stavudine should be avoided since an antagonistic relationship has been demonstrated in vitro. In addition, concomitant use of zidovudine with doxorubicin or ribavirin should be avoided because an antagonistic relationship has also been demonstrated in vitro.

Contraindications

Contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product

Side Effects

Hypersensitivity reaction, GI disturbance, anorexia, headache, insomnia, muscle disorder, cough, rash, alopecia, fever, fatigue, malaise, severe hepatomegaly.

Pregnancy & Lactation

Pregnancy Category C. There are no adequate and well-controlled studies of abacavir / Lamivudine / Zidovudine in pregnant women. This drug should be used during pregnancy only if the potential benefits outweigh the risks.

The Centers for Disease Control and Prevention recommend that HIVinfected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV infection.

Zidovudine is excreted in breast milk; abacavir and lamivudine are secreted into the milk of lactating rats. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving this combination.

Precautions

Hypersensitivity Reaction: This combination contains abacavir sulfate, which has been associated with fatal hypersensitivity reactions. Patients developing signs or symptoms of hypersensitivity should discontinue this combination as soon as a hypersensitivity reaction is first suspected, and should seek medical evaluation immediately.

Bone Marrow Suppression: Since this combination contains Zidovudine, it should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count <1,000 cells/mm3 or hemoglobin combination. For HIV-infected individuals and patients with asymptomatic or early HIV disease, periodic blood counts are recommended.

Myopathy: Myopathy and myositis, with pathological changes similar to that produced by HIV disease, have been associated with prolonged use of Zidovudine, and therefore may occur with therapy with this combination.

Post-treatment Exacerbations of Hepatitis:In clinical trials in non-HIV-infected patients treated with lamivudine for chronic hepatitis B (HBV), clinical and laboratory evidence of exacerbations of hepatitis after discontinuation of Lamivudine. Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.

Use in Special Population

This combination is not intended for use in pediatric patients. This combination tablet should not be administered to adolescents who weigh less than 40 kg because it is a fixed-dose tablet that cannot be adjusted for this patient population.

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