LAMIVUDINE/NEVIRAPINE/ZIDOVUDINE TABLETS
Clinical safety rating: safe
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV reverse transcriptase by competing with natural substrates and causing chain termination. Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to reverse transcriptase, causing conformational disruption. Zidovudine is an NRTI that inhibits viral reverse transcriptase after intracellular phosphorylation to its active triphosphate form.
| Metabolism | Lamivudine: Limited hepatic metabolism (∼5%) via endogenous metabolism; primarily renal excretion. Nevirapine: Extensively metabolized by hepatic CYP3A4 and CYP2B6. Zidovudine: Primarily hepatic glucuronidation via UGT2B7, with minor metabolism by CYP3A4. |
| Excretion | Lamivudine: ~70% renal (glomerular filtration and tubular secretion, unchanged). Nevirapine: ~80% biliary/fecal (metabolites), ~10% renal (unchanged). Zidovudine: ~75% renal (metabolism to glucuronide, tubular secretion). |
| Half-life | Lamivudine: 5-7h (adults), prolonged in renal impairment. Nevirapine: 25-30h (single dose), 40-45h (multiple doses, autoinduction). Zidovudine: 0.5-3h (terminal), prolonged in hepatic impairment. |
| Protein binding | Lamivudine: <36% (albumin). Nevirapine: 60% (albumin). Zidovudine: 30-38% (albumin). |
| Volume of Distribution | Lamivudine: 1.3 L/kg (distributes to total body water). Nevirapine: 1.2 L/kg (extensive tissue distribution, including CNS). Zidovudine: 1.6 L/kg (penetrates CNS, CSF:plasma ratio ~0.6). |
| Bioavailability | Lamivudine: 80-88% (oral). Nevirapine: >90% (oral). Zidovudine: 60-70% (oral, first-pass metabolism). |
| Onset of Action | Oral: Lamivudine antiviral effect within 2-4h; Nevirapine reduces HIV RNA within 2 weeks; Zidovudine reduces viral load within 2-4 weeks. |
| Duration of Action | Lamivudine: 12h (standard dosing interval). Nevirapine: 12h (dosing interval), sustained due to long half-life. Zidovudine: 4-8h (dosing dependent). |
| Molecular Weight | Lamivudine: 229.3 Da; Nevirapine: 266.3 Da; Zidovudine: 267.2 Da |
One tablet (150 mg lamivudine/200 mg nevirapine/300 mg zidovudine) orally twice daily.
| Dosage form | TABLET, FOR SUSPENSION |
| Renal impairment | If creatinine clearance 30-49 mL/min: use separate components; lamivudine 150 mg once daily, zidovudine 300 mg twice daily, nevirapine 200 mg twice daily. If <30 mL/min or on hemodialysis: avoid fixed-dose combination; use individual components. |
| Liver impairment | Child-Pugh A or B: nevirapine contraindicated due to hepatotoxicity risk; avoid fixed-dose combination. Child-Pugh C: contraindicated. |
| Pediatric use | Weight ≥14 kg: one tablet twice daily. If unable to swallow tablets, use individual components. Weight 6-13.9 kg: use liquid formulations (lamivudine 4 mg/kg, nevirapine 7 mg/kg, zidovudine 8-10 mg/kg twice daily). |
| Geriatric use | Use with caution due to age-related renal and hepatic decline; monitor renal function and adjust dose as per renal adjustment. |
| 1st trimester | Data are insufficient to determine human teratogenic risk. Animal studies have shown limited evidence of risk, but potential benefits may warrant use in pregnant women at high risk of HIV transmission. Nevirapine has been associated with increased risk of hepatotoxicity in pregnant women with CD4 >250 cells/mm3. Use with caution. |
| 2nd trimester | Can be used as part of combination antiretroviral therapy for HIV. Monitor for hepatotoxicity, especially with nevirapine. No evidence of teratogenicity in second trimester. |
| 3rd trimester | Safe for use as part of combination therapy. May reduce risk of perinatal transmission. Monitor maternal liver function and hematologic parameters due to zidovudine and lamivudine. Nevirapine can cause severe hepatotoxicity; consider alternative if CD4 >250. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
| FDA category | Human |
| Placental transfer |
■ FDA Black Box Warning
Nevirapine: Severe, life-threatening hepatotoxicity and skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis) have occurred. Zidovudine: Hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV disease. Also, prolonged use has been associated with symptomatic myopathy.
| Common Effects | Anemia |
| Serious Effects |
Hypersensitivity to any componentSevere hepatic impairment (Child-Pugh C) for nevirapineConcomitant use with other nevirapine-containing productsLife-threatening adverse reactions to any of the components (e.g., Stevens-Johnson syndrome with nevirapine)Severe anemia or neutropenia due to zidovudineRenal impairment requiring dose adjustment not possible with fixed-dose combination
| Precautions | Hepatotoxicity: Nevirapine can cause severe, life-threatening hepatotoxicity, including hepatic failure, especially in women with CD4 >250 cells/mm³ and men with CD4 >400 cells/mm³., Skin reactions: Nevirapine associated with severe rash; patient should be monitored closely during first 18 weeks., Hematologic toxicity: Zidovudine may cause neutropenia and anemia; monitor blood counts., Lactic acidosis and severe hepatomegaly with steatosis: Reported with NRTIs, including zidovudine and lamivudine., Immune reconstitution syndrome., Lipodystrophy and metabolic effects., Use with caution in patients with hepatic impairment., Pancreatitis, especially in pediatric patients. |
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| All three drugs cross the placenta. Lamivudine and zidovudine reach cord blood levels similar to maternal plasma; nevirapine also crosses readily. Zidovudine is known to achieve therapeutic concentrations in the fetus. |
| Breastfeeding | Breastfeeding is not recommended in HIV-infected women due to risk of HIV transmission via breast milk. All three drugs are excreted into human milk. In settings where formula feeding is not feasible, the benefits of breastfeeding may outweigh the risk of drug exposure, but this should be discussed with the healthcare provider. Monitor infant for adverse effects such as anemia (zidovudine) and hepatotoxicity (nevirapine). |
| Lactation Rating | L4 (Possibly Hazardous) - Contraindicated in breastfeeding due to HIV transmission risk. |
| Teratogenic Risk | Lamivudine/nevirapine/zidovudine: Pregnancy category C (individual components). First trimester: Zidovudine associated with possible mitochondrial toxicity, nevirapine with increased risk of rash and hepatotoxicity; no major human teratogenicity. Second/third trimester: No increase in birth defects; zidovudine reduces HIV vertical transmission by 67% (ACTG 076). |
| Fetal Monitoring | Maternal: Complete blood count, hepatic transaminases, HIV RNA viral load, CD4 count at baseline and every 1-2 months. Fetal: Ultrasound for growth and anatomy; neonatal monitoring for anemia, neutropenia, mitochondrial dysfunction. |
| Fertility Effects | No significant negative effects on female or male fertility reported. Zidovudine may cause transient sperm abnormalities in animal studies; clinical relevance unknown. |
| Food/Dietary | No significant food interactions; absorption not affected by food. Avoid grapefruit juice if also taking protease inhibitors, though not part of this fixed-dose combination. Maintain adequate hydration to prevent crystalluria from other antiretrovirals. |
| Clinical Pearls | Fixed-dose combination for HIV-1 infection; nevirapine requires lead-in dosing of 200 mg daily for 14 days before escalating to twice daily; monitor for hepatotoxicity and severe skin reactions, especially in females with CD4 >250 cells/mm³ and males with CD4 >400 cells/mm³; zidovudine associated with hematologic toxicity; lamivudine active against both HIV-1 and HBV but not recommended as monotherapy for HBV; avoid in patients with creatinine clearance <50 mL/min due to zidovudine accumulation. |
| Patient Advice | Take this medication exactly as prescribed; do not miss doses to prevent drug resistance. · This combination does not cure HIV; it reduces viral load and improves immune function. · Report any rash, especially if accompanied by fever, blisters, or mucosal ulcers, immediately. · Watch for signs of liver damage: yellow skin/eyes, dark urine, pale stools, nausea, vomiting, or abdominal pain. · Zidovudine may cause anemia; report unusual tiredness, paleness, or shortness of breath. · Take with or without food; if nausea occurs, take with food. · Avoid alcohol to reduce risk of liver toxicity. · Use effective contraception; nevirapine can reduce hormonal contraceptive efficacy. |