Lamivudine, nevirapine, and zidovudine tablets, a combination of two nucleoside analogue reverse transcriptase inhibitors (lamivudine and zidovudine) and one non-nucleoside analogue reverse transcriptase inhibitor (nevirapine), is indicated alone as a complete regimen or in combination with other antiretroviral drugs for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg. Limitation of Use: Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, lamivudine, nevirapine, and zidovudine tablets is not recommended to be initiated, unless the benefit outweighs the risk, in: ? adult females with CD4+ cell counts greater than 250 cells per mm3 ? adult males with CD4+ cell counts greater than 400 cells per mm
Drugs for HIV / Anti-retroviral drugs
Lamivudine, Zidovudine & Nevirapine synergistically reduce the viral resistance and inhibit reverse transcriptase via DNA chain termination.
Lamivudine: Intracellularly, Lamivudine is phosphorylated to its active 5’-triphosphate metabolite, Lamivudine triphosphate (L-TP). The principal mode of action of L-TP is inhibition of reverse transcription (RT) via DNA chain termination after incorporation of the nucleoside analogue. Following oral administration, Lamivudine is rapidly absorbed and extensively distributed. Binding to plasma protein is low.
Zidovudine: Intracellularly, Zidovudine is phosphorylated to its active 5’-triphosphate metabolite, Zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of RT via DNA chain termination after incorporation of the nucleoside analogue. Following oral administration, Zidovudine is rapidly absorbed and extensively distributed. Binding to plasma protein is low. Zidovudine is eliminated primarily by hepatic metabolism.
Nevirapine: Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates.
The 14-day lead-in period with nevirapine 200 mg once daily must be strictly followed; it has been demonstrated to reduce the frequency of rash. ? If any patient experiences rash during the 14-day lead-in period, do not dose escalate to 200 mg twice daily until the rash has resolved. Do not continue the lead-in dosing regimen beyond 28 days. ? If dosing is interrupted for greater than 7 days, restart 14-day nevirapine lead-in period. ? Because lamivudine, nevirapine, and zidovudine tablets is a fixed dose combination and cannot be dose adjusted, lamivudine, nevirapine, and zidovudine tablets is not recommended in pediatric patients weighing less than 35 kg, patients with creatinine clearance less than 50 mL per minute, patients with hepatic impairment or experiencing dose-limiting adverse reactions. Adults and Pediatric Patients Weighing at Least 35 kg First 14 days One lamivudine, nevirapine, and zidovudine fixed-dose tablet once daily followed by a daily oral dose of lamivudine and zidovudine 12 hours later After 14 days One lamivudine, nevirapine, and zidovudine fixed-dose tablet twice daily
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).
In patients with previously hypersensitivity . ? In patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment . ? Use as part of occupational and non-occupational post-exposure prophylaxis (PEP) regimens, an unapproved use
Most commonly reported adverse reactions (incidence greater than or equal to 15%) in clinical trials of combination lamivudine and zidovudine were nausea, headache, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough. ? Nevirapine: The most common adverse reaction is rash. In adults the incidence of rash is 15% versus 6% with placebo, with Grade 3/4 rash occurring in 2% of subjects. ? Nevirapine: In pediatric subjects the incidence of rash (all causality) was 21%.
Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.Lactation: Women infected with HIV should be instructed not to breastfeed due to the potential for HIV transmission.
Should be stored in cool and dry place
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