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. |
| Molecular Weight | Lamivudine: 229.3 Da; Zidovudine: 267.2 Da; Nevirapine: 266.3 Da. Note: This is a combination product; each component has listed MW. |
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 | Lamivudine/zidovudine: Limited human data; animal studies show embryotoxicity at high doses. Nevirapine: Human data suggest no increased risk of major malformations. Generally considered acceptable if benefit outweighs risk; use with caution. |
| 2nd trimester | Lamivudine/zidovudine: No evidence of fetal harm from human studies; well-tolerated. Nevirapine: No increased risk of malformations; monitor for hepatotoxicity. Acceptable for HIV treatment during pregnancy. |
| 3rd trimester | Lamivudine/zidovudine: Recommended for prevention of perinatal HIV transmission; extensive safety data. Nevirapine: Used for prevention of mother-to-child transmission; generally safe. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
| FDA category | Human |
| Placental transfer | Lamivudine: extensive placental transfer with cord blood levels similar to maternal plasma. Zidovudine: readily crosses placenta; achieves therapeutic levels in fetus. Nevirapine: extensive placental transfer; crosses rapidly. |
■ 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 lamivudine, zidovudine, or nevirapineSevere hepatic impairment (Child-Pugh class B or C) for nevirapineSevere renal impairment (CrCl <30 mL/min) for lamivudine/zidovudine componentLife-threatening cutaneous reactions (e.g., Stevens-Johnson syndrome) with previous nevirapine use
| Precautions | Hematologic toxicity, hepatic toxicity, lactic acidosis, pancreatitis, immune reconstitution syndrome, lipodystrophy, exacerbation of hepatitis B (lamivudine), hypersensitivity reactions (nevirapine), and risk of resistance. |
| Food/Dietary |
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| 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. |
| Breastfeeding | Lamivudine and zidovudine are excreted into human milk; nevirapine is also excreted. In HIV-infected mothers, breastfeeding is not recommended to avoid postnatal transmission of HIV. If maternal HIV is suppressed and no alternative feeding is available, benefits may outweigh risks; infant should be monitored for toxicity. |
| Lactation Rating | L4 (Possibly Hazardous) - Avoid breastfeeding due to HIV transmission risk; in exceptional cases, use with caution. |
| 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. |
| Take with food to reduce gastrointestinal side effects; no specific food interactions. Avoid alcohol due to risk of hepatotoxicity with nevirapine. |
| Clinical Pearls | Fixed-dose combination for HIV-1 treatment; monitor for hepatotoxicity and severe rash within first 18 weeks of nevirapine therapy, especially in women with CD4 >250 cells/mm³ or men with CD4 >400 cells/mm³. Zidovudine causes macrocytic anemia and neutropenia; monitor CBC. Lamivudine/zidovudine may cause lactic acidosis and hepatomegaly with steatosis. Administer with food to reduce GI upset; nevirapine induces CYP3A4, reducing levels of oral contraceptives and methadone. |
| Patient Advice | Take exactly as prescribed; do not miss doses to prevent resistance. · Report any rash, especially if accompanied by fever, blisters, or mouth sores, as nevirapine can cause severe skin reactions. · Common side effects include nausea, headache, and fatigue; these often improve over time. · Zidovudine may cause low red blood cell counts (anemia) and low white cell counts; report unusual tiredness, paleness, or infections. · Lamivudine/zidovudine can rarely cause lactic acidosis (symptoms: deep breathing, vomiting, stomach pain) and liver problems (yellow skin/eyes, dark urine). · This combination does not cure HIV or prevent transmission; practice safe sex and avoid sharing needles. · Inform all healthcare providers you are taking this medication, especially before starting new drugs. · Nevirapine may reduce effectiveness of hormonal contraceptives; use additional or alternative contraception. |