lamivudine + zidovudine: clinical use

Prescribing considerations

• Initiate and supervise within experienced HIV care as part of combination antiretroviral therapy.
• Assess renal and hepatic function, baseline haematological status, hepatitis B or C co-infection and concomitant medicines.
• The fixed combination is unsuitable when either component requires individual adjustment.
• Monitor for lipoatrophy, pancreatitis, lactic acidosis, immune reconstitution inflammatory reactions and liver deterioration.
• Stopping lamivudine in HIV/HBV co-infection can precipitate hepatitis B exacerbation.

Contraindications and cautions

• Hypersensitivity to lamivudine, zidovudine or an excipient.
• Neutrophils below 0.75 × 10^9/L.
• Haemoglobin below 7.5 g/dL or 4.65 mmol/L.

Monitoring

• Full blood count, particularly for anaemia, neutropenia and leucopenia.
• HIV viral load, CD4 count and clinical response.
• Renal and hepatic function, with enhanced surveillance where impairment or interacting toxicity is present.
• Body-fat distribution, blood lipids and glucose.
• After discontinuation in HIV/HBV co-infection, monitor liver function and HBV replication markers because hepatitis may flare.

Clinical pharmacology

Both components are phosphorylated inside cells to active triphosphates that inhibit HIV-1 and HIV-2 reverse transcriptase through viral DNA-chain termination. Lamivudine is predominantly eliminated unchanged by the kidneys; zidovudine is mainly glucuronidated. Major cytochrome P450 interactions are unlikely.

Formulation and product differences

• The scored film-coated fixed-combination tablet can be divided into equal halves.
• It may be crushed into a small amount of food or liquid and consumed immediately when swallowing whole tablets is not possible.
• Use separate preparations when individual adjustment or discontinuation of one component is required.

Tablet

Route: Oral

Strengths: 150 mg + 300 mg