LAMIVUDINE; NEVIRAPINE; ZIDOVUDINE
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 competing with natural nucleosides and causing chain termination. Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to reverse transcriptase and disrupts its catalytic site.
| Metabolism | Lamivudine: minimally metabolized (5-10%) via endogenous metabolism; primarily renal excretion. Nevirapine: metabolized by CYP3A4 and CYP2B6. Zidovudine: metabolized via glucuronidation (glucuronosyltransferase) and renal excretion. |
| Excretion | Lamivudine: ~70% renal (unchanged); Nevirapine: ~80% renal (metabolites), ~10% fecal; Zidovudine: ~75% renal (metabolite zidovudine glucuronide). |
| Half-life | Lamivudine: 5–7 hours in adults; Nevirapine: 25–30 hours (initial monotherapy), 20–25 hours (steady state); Zidovudine: 0.5–3 hours (mean 1.1 hours). |
| Protein binding | Lamivudine: <36% (primarily albumin); Nevirapine: 60% (albumin); Zidovudine: 25–38% (albumin). |
| Volume of Distribution | Lamivudine: 1.3 L/kg; Nevirapine: 1.2–1.5 L/kg; Zidovudine: 1.4 L/kg (indicates extensive tissue distribution, including CNS). |
| Bioavailability | Lamivudine: 86% (oral); Nevirapine: >90% (oral); Zidovudine: 60–70% (oral). |
| Onset of Action | Oral: Lamivudine and Zidovudine reach peak plasma concentrations in 0.5–2 hours; Nevirapine reaches peak in 4 hours. Clinical antiviral effect begins within days, with maximal suppression over weeks. |
| Duration of Action | Lamivudine: 12 hours (recommended dose interval); Nevirapine: 12 hours (dosing interval requires twice-daily dosing); Zidovudine: 4–8 hours (short duration, requires frequent dosing). Clinical suppression requires continuous therapy; discontinuation leads to rapid viral rebound. |
One tablet (lamivudine 150 mg / nevirapine 200 mg / zidovudine 300 mg) orally twice daily.
| Dosage form | TABLET |
| Renal impairment | If creatinine clearance <50 mL/min, use separate components: lamivudine dose adjust per renal function (e.g., 150 mg q24h if CrCl 30-49, 150 mg first dose then 100 mg q24h if CrCl 15-29, 150 mg first dose then 50 mg q24h if CrCl 5-14, 150 mg first dose then 25 mg q24h if CrCl <5 or hemodialysis); nevirapine no adjustment; zidovudine dose adjust (e.g., 300 mg q12h if CrCl ≥15, 300 mg q24h if CrCl <15). |
| Liver impairment | Contraindicated in Child-Pugh class B or C; for Child-Pugh class A, no dose adjustment recommended but monitor closely; nevirapine should not be used in patients with moderate to severe hepatic impairment. |
| Pediatric use | Weight-based dosing: For body weight ≥30 kg, one tablet (150/200/300 mg) twice daily; for 25-29 kg, use oral solutions: lamivudine 4 mg/kg twice daily, nevirapine 7 mg/kg (or 120 mg/m2) twice daily, zidovudine 240 mg/m2 twice daily (max 300 mg); for 14-24 kg, lamivudine 4 mg/kg twice daily, nevirapine 7 mg/kg (or 120 mg/m2) twice daily, zidovudine 240 mg/m2 twice daily (max 300 mg). |
| Geriatric use | No specific dose adjustments; use with caution due to age-related renal and hepatic decline; monitor renal function and hematologic parameters closely. |
| 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 | Both lamivudine and zidovudine are excreted into human breast milk with moderate concentrations. Nevirapine also excretes into milk. The milk-to-plasma ratio for lamivudine is approximately 3.6; for zidovudine, about 3.0; for nevirapine, about 0.7. Breastfeeding is not recommended for HIV-infected mothers in developed settings due to risk of HIV transmission; however, if breastfeeding is unavoidable, the infant will receive subtherapeutic drug exposure. No data on long-term effects in nursing infants, but theoretical risk of adverse effects (e.g., hematologic toxicity). |
■ FDA Black Box Warning
Hematologic toxicity (including neutropenia and severe anemia) associated with zidovudine; hepatic toxicity (including symptomatic hepatic events and hepatic failure) and severe, life-threatening skin reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis) associated with nevirapine; lactic acidosis and severe hepatomegaly with steatosis reported with NRTIs.
| Common Effects | Anemia |
| Serious Effects |
Prior hypersensitivity to any component; severe hepatic impairment (Child-Pugh class C); concomitant use with certain medications (e.g., rifampin, St. John's wort, etravirine).
| Precautions | Hepatotoxicity with nevirapine (highest risk in women with CD4 >250 cells/mm³ and men with CD4 >400 cells/mm³); severe skin reactions (nevirapine); hematologic toxicity (zidovudine); lactic acidosis/hepatic steatosis; immune reconstitution syndrome; lipodystrophy; mitochondrial toxicity; pancreatitis; monitor LFTs, CBC, and skin reactions. |
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| Teratogenic Risk | Lamivudine, nevirapine, and zidovudine are all Pregnancy Category C. Zidovudine crosses the placenta and has been associated with a possible increased risk of mitochondrial dysfunction in infants with in utero exposure, although overall risk of major malformations is low. Nevirapine has been linked to hepatotoxicity in pregnant women, especially those with CD4 >250 cells/mm³, but not specifically teratogenic. Lamivudine is not associated with increased birth defects. In first trimester, data do not show a significant increase in malformations; second and third trimester use is generally considered safe for HIV treatment, but risk of anemia and neutropenia in neonates with zidovudine may occur. |
| Fetal Monitoring | Maternal: Complete blood count (CBC) with differential and platelets at baseline and every 3-4 weeks; liver function tests (LFTs) at baseline and frequently in first 18 weeks of nevirapine therapy, especially if CD4 >250 cells/mm³; plasma HIV RNA viral load and CD4 count every 3-4 weeks; glucose tolerance test due to zidovudine-associated hyperglycemia; fetal: ultrasound for growth and anatomy; neonatal: CBC at birth and within first weeks; monitor for hyperbilirubinemia; HIV testing per protocol. |
| Fertility Effects | No known significant negative impact on fertility. In animal studies, no effects on mating or fertility were observed with lamivudine or zidovudine. Nevirapine has not been associated with fertility impairment. HIV infection itself can affect fertility; antiretroviral therapy improves overall health and may restore fertility. |