Adult: Each tab contains lamivudine 150 mg and zidovudine 300 mg: >30 kg: 1 tab bid. Child: 14-21 kg: One-half tab bid; 22-30 kg: One-half tab in the morning, 1 tab at night, or one-half tab tid; >30 kg: 1 tab bid.
Not recommended, use separate preparations.
Severe: Not recommended, use separate preparations.
May be taken with or without food.
Hypersensitivity. Abnormally low neutrophil counts (<0.75 x 109/L) or Hb levels (<7.5 g/dL or 4.65 mmol/L). Lactation. Concomitant use w/ interferon alfa (w/ or w/o ribavirin) in HIV and hepatitis B or C virus co-infected patients.
Patient w/ poor bone marrow reserve prior to treatment; obese women w/ hepatomegaly, hepatitis or other risk factors for liver disease and hepatic steatosis; hepatitis B or C virus co-infection; history or risk factors for pancreatitis. Renal and severe hepatic impairment. Childn. Pregnancy.
Monitor haematological parameters (e.g. CBC w/ platelet count); observe for appearance of opportunistic infections and signs and symptoms of pancreatitis. Periodically monitor LFTs and for several mth following discontinuation of therapy for patients co-infected w/ hepatitis B virus and HIV.
Cross-resistance may develop when given w/ emtricitabine. Exacerbation of anaemia w/ concomitant use of zidovudine w/ ribavirin. Increased adverse effects to zidovudine w/ nephrotoxic or myelosuppressive drugs (e.g. systemic pentamide, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine, doxorubicin). Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Antagonistic effect when zidovudine is used concomitantly w/ stavudine or doxorubicin. Potentially Fatal: Risk of hepatic decompensation when used concomitantly w/ interferon alfa (w/ or w/o ribavirin) in HIV and hepatitis B or C virus co-infected patients.
Description: Mechanism of Action: Lamivudine and zidovudine synergistically reduce viral resistance and inhibit reverse transcriptase via DNA chain termination and delay the emergence of mutations conferring resistance. Pharmacokinetics: Absorption: Rapidly absorbed from the GI tract. Delayed absorption w/ food. Bioavailability: 80-87% (lamivudine); approx 60-70% (zidovudine). Time to peak plasma concentration: Approx 1 hr. Distribution: Crosses the blood-brain barrier and placenta; enters breast milk. Detected in semen (zidovudine). Volume of distribution: 1.3 L/kg (lamivudine); 1-2.2 L/kg (zidovudine). Plasma protein binding: Up to 36% (lamivudine); 34-38% (zidovudine). Metabolism: Both are metabolised intracellularly to the active triphosphate form. Zidovudine undergoes hepatic metabolism, mainly to the inactive glucuronide. Excretion: Via urine, mainly as unchanged drug. Elimination half-life: 5-7 hr (lamivudine); 0.5-3 hr (zidovudine).