Lamivudine + Zidovudine

Indications

Lamivudine + Zidovudine is used for: HIV infection

Adult Dose

Oral HIV infection Adult: Each tab contains lamivudine 150 mg and zidovudine 300 mg: >30 kg: 1 tab bid. Avoid administering to patients < 30 kg Hepatic impairment: Severe: Not recommended, use separate preparations.

Child Dose

HIV Infection <12 years: Not recommended; fixed-dose combination cannot be adjusted for children > 12 years and < 30 kg: Not recommended >12 years and >30 kg: As adults; 150 mg/300 mg (1 tablet) PO q12hr

Renal Dose

Renal impairment: CrCl (ml/min) Dosage Recommendation <50 Not recommended, use separate preparations

Administration

May be taken with or without food.

Contra Indications

Neutrophil count <0.75 x 109/l; haemoglobin levels <7.5 g/dl or 4.65 mmol/l. Lactation.

Precautions

Renal and hepatic impairment; poor bone marrow reserve prior to treatment; risk of opportunistic infection; patients (especially obese women) with risk factors for or active liver disease. Patients with low body wt should avoid the combined formulation. Separate formulations of lamivudine or zidovudine should not be given at the same time as the combined formulation. If dose adjustment is necessary for either component, separate formulations should be used. Monitor haematological parameters (advanced disease: 2 wkly for 1st 3 mth of treatment, then monthly; early disease: 1-3 mthly), LFTs, mean cell volume, serum creatinine kinase, viral load, CD4 counts and blood lactate levels. Patient to report any sore throat, nausea, vomiting, unexplained bruising or bleeding. Maintain adequate hydration (2-3 L/day) unless fluid restricted. Withdraw treatment if symptomatic hyperlactaemia, metabolic/lactic acidosis, progressive heptomegaly or rapidly elevating aminotransferase levels occur. Cases of lactic acidosis and hepatic steatosis syndrome have been reported in pregnancy. Monitor hepatic enzymes and electrolytes regularly during 3rd trimester. Lactation: not recommended

Pregnancy-Lactation

Interactions

Zidovudine: acyclovir and valacyclovir may increase CNS depression. Increased risk of haematologic toxicity with ganciclovir, valganciclovir, dapsone, doxorubicin, vincristine and vinblastine. Doxorubicin may reduce phophorylation; fluconazole may increase levels/effects; increased risk of hepatic decompensation or haematologic toxicities with interferon-? and ribavirin (also increases risk of pancreatitis and lactic acidosis). Methadone may increase effects/levels. Increased risk of myalgia, malaise and/or fever, maculopapular rash and effects/levels with probenecid. Stavudine may decrease antiviral activity; valproic acid may increase plasma levels (AUC increased by 80%). Lamivudine: Increased risk of hepatic decompensation or haematologic toxicities with interferon-? and ribavirin (also increases risk of mitochondrial toxicity, pancreatitis and lactic acidosis). Ganciclovir and valganciclovir may increase effects and toxicity; sulfamethoxazole/trimethoprim may increase AUC and decrease clearance (increasing levels and effects).

Adverse Effects

Side effects of Lamivudine + Zidovudine : >10% Headache (35%),Nausea (33%),Malaise & fatigue (27%),Cough (18%),Diarrhea (18%),Vomiting (13%),Musculoskeletal pain (12%),Neuropathy (12%),Insomnia & other sleep disorders (11%) 1-10% Anorexia &/or decreased appetite (10%),Dizziness (10%),Fever or chills (10%),Abdominal pain (9%),Depressive disorders (9%),Skin rashes (9%),Myalgia (8%),Neutropenia (7.2% ),Abdominal cramps (6%),Arthralgia (5%),Dyspepsia (5%),Anemia (2.9% ) Frequency Not Defined (serious) Erythema multiforme,Stevens-Johnson syndrome,Lactic acidosis,Pancreatitis,Hepatomegaly (Severe),Steatosis of liver (Severe),Anaphylaxis,Immune hypersensitivity reaction,Rhabdomyolysis Potentially Fatal: Lactic acidosis associated with liver failure and pancreatitis (normally after several mth of treatment); haematological toxicity (eg neutropenia and severe anaemia).

Mechanism of Action

Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog Zidovudine: NRTI; interferes with HIV viral RNA-dependent DNA polymerase (inhibits viral replication); thymidine analog