Lamivudine/Zidovudine 150 mg/300 mg Tablets Co-packaged with Nevirapine 200 mg Tablets
Clinical safety rating: safe
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
Lamivudine and zidovudine are nucleoside reverse transcriptase inhibitors (NRTIs) that inhibit HIV-1 reverse transcriptase by competitive inhibition and chain termination. Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to reverse transcriptase and blocks RNA-dependent and DNA-dependent DNA polymerase activities.
| Metabolism | Lamivudine: primarily renally excreted unchanged. Zidovudine: hepatic glucuronidation (UGT2B7). Nevirapine: hepatic via CYP3A4 and CYP2B6. |
| Excretion | Lamivudine: primarily renal excretion of unchanged drug (approximately 70% within 24 hours) via glomerular filtration and active tubular secretion. Zidovudine: renal excretion (approximately 14% unchanged) and hepatic metabolism to GAZT (glucuronide), with 74% of dose recovered in urine as total zidovudine and metabolites. Nevirapine: 81% of dose recovered in urine (primarily metabolites) and 10% in feces; <5% excreted unchanged in urine. |
| Half-life | Lamivudine: terminal half-life 5-7 hours in adults; prolonged in renal impairment. Zidovudine: terminal half-life 1.1-1.3 hours; prolonged to 1.7 hours in renal impairment. Nevirapine: terminal half-life 45 hours (single dose), reducing to 25-30 hours after multiple dosing due to autoinduction. |
| Protein binding | Lamivudine: <36% bound to plasma albumin. Zidovudine: 20-40% bound to plasma proteins (mainly albumin). Nevirapine: 60% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Lamivudine: 1.3 L/kg, indicating wide distribution beyond plasma. Zidovudine: 1.6 L/kg, extensive distribution including into CSF (CSF-to-plasma ratio ~0.5). Nevirapine: 1.2 L/kg, with extensive tissue distribution and good penetration into CSF (CSF concentration ~45% of plasma). |
| Bioavailability | Lamivudine: oral bioavailability 86-88% in adults, not significantly affected by food. Zidovudine: oral bioavailability 60-70% (fasting), reduced by food. Nevirapine: oral bioavailability >90% (tablet), not significantly affected by food. |
| Onset of Action | Lamivudine: not applicable (no direct clinical effect). Zidovudine: not applicable. Nevirapine: onset of antiretroviral effect occurs within days; however, due to autoinduction, full steady-state concentrations and maximal effect are not achieved until after 2-4 weeks of dosing. |
| Duration of Action | Lamivudine: dosing interval 12 hours; requires daily administration. Zidovudine: dosing interval 12 hours; short half-life necessitates twice-daily dosing. Nevirapine: dosing interval 12 hours after 14-day lead-in with 200 mg once daily; duration of action supports twice-daily dosing at steady state. |
One tablet (lamivudine 150 mg/zidovudine 300 mg) orally twice daily, plus one tablet (nevirapine 200 mg) orally once daily for first 14 days, then one tablet (nevirapine 200 mg) orally twice daily thereafter.
| Dosage form | TABLET |
| Renal impairment | For CrCl ≥50 mL/min: no adjustment. For CrCl 30-49 mL/min: lamivudine/zidovudine dose reduce to 150 mg/150 mg twice daily. For CrCl <30 mL/min: lamivudine/zidovudine not recommended. Nevirapine: no dose adjustment required for renal impairment, but not studied in severe renal impairment (CrCl <20 mL/min). |
| Liver impairment | Lamivudine: no dose adjustment in mild-moderate hepatic impairment; not studied in severe. Zidovudine: no data; caution in hepatic impairment. Nevirapine: do not use in Child-Pugh class B or C (contraindicated). Child-Pugh A: no dose adjustment, but monitor closely. |
| Pediatric use | Lamivudine/zidovudine: For children ≥12 years and ≥30 kg, same as adult dosing (one tablet twice daily). For children <12 years or <30 kg, use individual components. Nevirapine: For children ≥12 years and ≥30 kg, same as adult dosing (200 mg once daily for 14 days, then 200 mg twice daily). For children <12 years or <30 kg, weight-based dosing: 150 mg/m² once daily for 14 days, then 150 mg/m² twice daily; maximum 200 mg/dose. |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
| FDA category | Human |
| Breastfeeding | Zidovudine and lamivudine are excreted into breast milk with M/P ratios of approximately 0.5-1.0 and 3.5-5.0, respectively. Nevirapine has high breast milk penetration (M/P ~0.6-1.0). In HIV-positive mothers, breastfeeding is contraindicated in developed countries due to potential transmission; in resource-limited settings, WHO recommends lifelong ART including this regimen with continued breastfeeding. Weigh benefits of breastfeeding against risk of HIV transmission. |
■ FDA Black Box Warning
Hematologic toxicity (neutropenia, anemia), myopathy, hepatotoxicity, lactic acidosis, severe hepatomegaly with steatosis, exacerbation of hepatitis B (lamivudine), and severe hypersensitivity reactions (nevirapine) including hepatotoxicity, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
| Common Effects | Anemia |
| Serious Effects |
Hypersensitivity to any component, coadministration with St. John's wort or rifampin, severe hepatic impairment, and patients with moderate-to-severe hepatic impairment (Child-Pugh B or C) for nevirapine.
| Precautions | Hematologic toxicity, hepatic toxicity, lactic acidosis, pancreatitis, immune reconstitution syndrome, lipodystrophy, exacerbation of hepatitis B (lamivudine), hypersensitivity reactions (nevirapine), and risk of resistance. |
Loading safety data…
| Use with caution due to age-related renal and hematologic decline. Monitor renal function and hemoglobin; adjust lamivudine/zidovudine dose based on CrCl. No specific nevirapine dose adjustment recommended, but monitor for hepatotoxicity and skin reactions. |
| Teratogenic Risk |
| Zidovudine: No increased risk of major malformations; crosses placenta; associated with transient neonatal anemia and neutropenia. Lamivudine: No increased risk of congenital anomalies; crosses placenta. Nevirapine: Limited data; no increased risk of major malformations; risk of hepatotoxicity in pregnant women with CD4>250 cells/mm³. First trimester: Risk is not significantly elevated above baseline. Second/third trimester: Continue for HIV treatment; monitor for anemia and neutropenia in neonate. |
| Fetal Monitoring | Maternal: Complete blood count with differential every 4 weeks; liver function tests, especially in nevirapine initiation; HIV viral load every 2-4 weeks until undetectable; CD4 count every 3 months. Fetal/neonatal: Ultrasound for growth and development; neonatal CBC at birth and at 4-6 weeks to detect anemia or neutropenia; serologic testing for HIV status. |
| Fertility Effects | Limited data. Zidovudine and lamivudine have no known significant impact on fertility in humans. Nevirapine may affect ovarian function (anecdotal reports of menstrual irregularities) but no conclusive evidence of impaired fertility. In men, no documented effects on spermatogenesis. Overall, no clear evidence of adverse effects on fertility. |