Abacavir + Lamivudine + Zidovudine

Oral
HIV infection

Dose adjustment may be necessary, separate preparations of abacavir, lamivudine and zidovudine should be administered.

Contraindicated.

May be taken with or without food.

Hypersensitivity to active ingredients; patients w/ ESRD, and abnormally low neutrophil count and haemoglobin level. Hepatic impairment. Lactation.

Patients co-infected w/ hepatitis B virus (HBV) and HIV. Screening for the HLA-B*5701 prior to treatment. Renal impairment. Pregnancy.

Haematologic toxicity (e.g. neutropenia, leucopenia and anaemia); anorexia; headache, insomnia, dizziness; cough, nasal symptoms; GI disturbances; elevated liver enzymes; rash, alopecia; arthralgia, myalgia; fatigue, malaise, fever; myopathy and myositis, lipodystrophy, MI, immune reactivation syndrome, insulin resistance, hyperlactataemia, hypertriglyceridaemia, hyperglycaemia, hypercholesterolaemia; hypertonia, abnormal behaviour, convulsions, hyperlipasaemia.
Potentially Fatal: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, anaphylaxis; renal and hepatic failure; fatal cases of lactic acidosis and severe hepatomegaly w/ steatosis; acute exacerbations of hepatitis B; pancreatitis.

PO: C

Monitor hepatic function, haematological paramaters (e.g. CBC).

Co-trimoxazole may increase the serum levels of lamivudine. Ganciclovir, interferon alfa, ribavirin, NSAIDs may increase haematotoxicity of zidovudine. Methadone may increase the the serum levels of zidovudine.

Alcohol may increase the serum levels of abacavir.

Description:
Mechanism of Action: Abacavir, lamivudine and zidovudine are all nucleoside reverse transcriptase inhibitors. Converted to their respective active triphosphate form, they act synergistically to reduce viral resistance and inhibit reverse transcriptase via DNA chain termination.
Pharmacokinetics:
Absorption: All are readily and well absorbed from the GI tract. Absolute bioavailability: Approx 83% (abacavir); between 80-87% (lamivudine); approx 60-70% (zidovudine). Time to peak plasma concentration: 0.5-1.7 hr (abacavir); approx 1 hr (lamivudine and zidovudine).
Distribution: All crosses blood-brain barrier; lamivudine and zidovudine also cross the placenta and are distributed into breast milk. Plasma protein binding: Approx 50% (abacavir); up to 36% (lamivudine); 34-38% (zidovudine).
Metabolism: Abacavir, lamivudine and zidovudine are metabolised by intracellular kinase to carbovir triphosphate (active triphosphate form of abacavir), lamivudine triphosphate and zidovudine triphosphate, respectively.
Excretion: All are mainly via urine (as unchanged drug and metabolite). Elimination half-life: Approx 1.5 hr (abacavir); 5-7 hr (lamivudine); approx 1 hr (zidovudine).

Do not store above 30°C.

Antivirals

J05AF06 - abacavir ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
J05AF01 - zidovudine ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
J05AF05 - lamivudine ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

Anon. Abacavir, Lamivudine, and Zidovudine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com.

Buckingham R (ed). Abacavir. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com.

Buckingham R (ed). Lamivudine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com.

Buckingham R (ed). Zidovudine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com.

McEvoy GK, Snow EK, Miller J et al (eds). Abacavir Sulfate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com.

McEvoy GK, Snow EK, Miller J et al (eds). Lamivudine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com.

McEvoy GK, Snow EK, Miller J et al (eds). Zidovudine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com.