Lamivudine + Nevirapine + Zidovudine

Indications

Lamivudine + Nevirapine + Zidovudine is used for: HIV infection

Adult Dose

Adult: PO: One tablet twice daily.

Child Dose

Renal Dose

Renal impairment: CrCl (ml/min) <50 Avoid

Administration

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.

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).

Side Effects

Side effects of Lamivudine + Nevirapine + Zidovudine : Headache, malaise and fatigue, fever or chills, nausea, diarrhoea, anorexia, abdominal pain, neuropathy, insomnia and other sleep disorders, dizziness, depressive disorders, nasal signs and symptoms, skin rashes, musculoskeletal pain, myalgia, arthralgia; anaemia, neutropenia and leucopenia (particularly at high doses of zidovudine; 1200-1500 mg/day), usually seen 4-5 wk after therapy commencing; respiratory symptoms eg rapid and/or deep breathing; if symptomatic hyperlactatemia, metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels occur, withdraw treatment; mitochondrial damage leading to hyperlactatemia and hyperlipasemia; lipodystrophy; immune reactivation syndrome, osteonecrosis. Potentially Fatal: Lactic acidosis associated with liver failure and pancreatitis (normally after several mth of treatment); haematological toxicity (eg neutropenia and severe anaemia).

Mode of Action

Synergistically reduce viral resistance and inhibit reverse transcriptase via DNA chain termination. 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. Nevirapine: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI); activity against HIV-1 by binding to reverse transcriptase, and thereby blocking RNA- and DNA-dependent DNA polymerase actions including HIV-1 replication. Does not require intracellular phosphorylation for activity.