Lamivudine + zidovudine

Oral
HIV infection
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.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
≤50	Not recommended, use separate preparations.

Hepatic impairment: 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. Monitoring Parameters 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.

Abdominal pain, nausea, vomiting, diarrhoea, dizziness, headache, fever, rash, alopecia, malaise, myalgia, insomnia, cough, nasal symptoms, arthralgia, musculoskeletal pain, immune reconstitution syndrome, lipodystrophy, metabolic abnormalities (e.g. hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia, hyperlactataemia), mitochondrial dysfunction (e.g. abnormal behaviour, anaemia, convulsions, hyperlipasaemia, hypertonia, neutropenia), osteonecrosis; increased creatine phosphokinase, liver enzymes, bilirubin and serum amylase; symptomatic myopathy and myositis. Rarely, rhabdomyolysis, pancreatitis, cardiomyopathy.
Potentially Fatal: Lactic acidosis, hepatomegaly w/ steatosis; haematologic toxicity (severe anaemia, neutropenia).

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.

Lamivudine and zidovudine synergistically reduce viral resistance and inhibit reverse transcriptase via DNA chain termination and delay the emergence of mutations conferring resistance.
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).

Oral: Store between 2-30°C.

Antivirals

J05AF05 - lamivudine ; 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.