zidovudine, lamivudine and nevirapine

J05AR05

Forms & Strengths

Fixed-dose combination tablet: Zidovudine 300 mg / Lamivudine 150 mg / Nevirapine 200 mg

Adult Dosing

One tablet orally twice daily
Lead-in dosing required for nevirapine component: One tablet daily for the first 14 days, then increase to twice daily if no rash or hepatotoxicity develops

Pediatric Dosing

Safety and efficacy of the fixed-dose combination tablet are not established in pediatric patients, particularly due to fixed ratio limitations
Individual component dosing is preferred for pediatric patients based on weight or body surface area

Indications

Mechanism of Action

Zidovudine (AZT): Thymidine nucleoside reverse transcriptase inhibitor (NRTI) that inhibits viral RNA-directed DNA polymerase
Lamivudine (3TC): Cytidine analogue NRTI that terminates viral DNA chain elongation
Nevirapine (NVP): Non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to HIV-1 reverse transcriptase, causing a disruption in catalytic activity

Contraindications

Hypersensitivity to zidovudine, lamivudine, nevirapine, or any component of the formulation
Moderate to severe hepatic impairment (Child-Pugh Class B or C)
Baseline AST or ALT greater than 5 times the upper limit of normal
History of nevirapine-associated severe rash, hypersensitivity reaction, or severe hepatotoxicity
Baseline absolute neutrophil count < 750 cells/mm3 or hemoglobin < 7.5 g/dL

Adverse Reactions

Severe hepatotoxicity including fatal hepatic necrosis
Severe skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS
Bone marrow suppression including severe anemia and neutropenia (zidovudine)
Lactic acidosis and severe hepatomegaly with steatosis
Nausea, fatigue, headache, insomnia, and myalgia
Pancreatitis, particularly in pediatric patients
Immune reconstitution inflammatory syndrome (IRIS)

Drug Interactions

CYP3A4/2B6 inducers (e.g., rifampin, St. John's wort) decrease nevirapine concentrations; coadministration is not recommended
CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) may increase nevirapine plasma concentrations
Methadone: Nevirapine may decrease plasma concentrations of methadone, potentially precipitating withdrawal
Hormonal contraceptives: Nevirapine may decrease their efficacy; alternative non-hormonal methods of contraception are recommended
Stavudine: Concomitant use with zidovudine is antagonistic and should be avoided
Emtricitabine: Avoid concomitant use with lamivudine due to overlapping resistance and lack of added benefit

Curated Content: Needs Vetting Before Put to Clinical Use