LAMIVUDINE, NEVIRAPINE AND 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 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 inhibits RNA-dependent DNA polymerase activity.
| Metabolism | Lamivudine: Limited hepatic metabolism (mostly excreted unchanged in urine). Nevirapine: Hepatic via CYP3A4 and CYP2B6. Zidovudine: Hepatic glucuronidation. |
| Excretion | Lamivudine: >70% unchanged in urine via glomerular filtration and active tubular secretion. Nevirapine: ~80% in urine as glucuronide conjugates and metabolites, <5% unchanged. Zidovudine: ~75% as metabolites (primarily zidovudine glucuronide) in urine, <20% unchanged. |
| Half-life | Lamivudine: 5-7 hours; Nevirapine: 25-30 hours (single dose), 40-45 hours with multiple dosing due to autoinduction; Zidovudine: 0.5-3 hours (mean 1.1 hours). Clinical context: Dosing interval adjusted for renal/hepatic function. |
| Protein binding | Lamivudine: <36% (albumin); Nevirapine: ~60% (albumin); Zidovudine: <38% (albumin). |
| Volume of Distribution | Lamivudine: 1.3 L/kg (distributes widely including CSF); Nevirapine: 1.2-1.5 L/kg (extensive tissue distribution); Zidovudine: 1.6 L/kg (penetrates CNS and CSF). |
| Bioavailability | Lamivudine: 86-90% (oral); Nevirapine: >90% (oral); Zidovudine: 60-70% (oral, variable due to first-pass metabolism). |
| Onset of Action | Oral: antiretroviral effect detectable within days; maximal viral load reduction by 4-8 weeks. |
| Duration of Action | Sustained viral suppression requires continuous dosing. Nevirapine has prolonged intracellular persistence despite short plasma half-life; clinical duration of action: 8-12 hours for zidovudine/lamivudine, 12-24 hours for nevirapine. |
One tablet (lamivudine 150 mg, nevirapine 200 mg, zidovudine 300 mg) orally twice daily.
| Dosage form | TABLET |
| Renal impairment | Not recommended for use when creatinine clearance <50 mL/min. For CrCl 50-80 mL/min: no adjustment. Not applicable for CrCl <30 mL/min due to fixed-dose combination. |
| Liver impairment | Contraindicated in Child-Pugh class B or C. For Child-Pugh class A: no dose adjustment but monitor closely. |
| Pediatric use | Children weighing ≥30 kg: same as adult dose (one tablet twice daily). For children <30 kg, use individual components. |
| Geriatric use | Caution due to age-related renal and hepatic impairment; monitor renal function and consider individual component dosing if CrCl <50 mL/min. |
| 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 | Lamivudine is excreted in human breast milk (M/P ratio ~3.3 for lamivudine; zidovudine M/P ratio ~0.8-1.0; nevirapine has high transfer, M/P ratio ~0.7-1.0). In HIV-infected women, breastfeeding is contraindicated in developed countries to avoid viral transmission; therefore, use of these drugs during lactation is generally not recommended. If prescribed, caution is advised due to potential infant toxicity. |
| Teratogenic Risk |
■ FDA Black Box Warning
Zidovudine: Hematologic toxicity, including neutropenia and severe anemia, especially in patients with advanced HIV disease; prolonged use associated with myopathy. Nevirapine: Severe, life-threatening hepatotoxicity and skin reactions (including Stevens-Johnson syndrome) have occurred, particularly in women with CD4+ counts >250 cells/mm³ and men with CD4+ counts >400 cells/mm³. Combination: Not recommended for prevention of occupational exposure to HIV.
| Common Effects | Anemia |
| Serious Effects |
Hypersensitivity to any component; nevirapine should not be restarted after severe hepatic or skin reactions; not recommended for use as single agent or in combination with other NNRTIs.
| Precautions | Hematologic toxicity (zidovudine); hepatotoxicity and severe skin reactions (nevirapine); immune reconstitution syndrome; lactic acidosis and severe hepatomegaly with steatosis; pancreatitis (especially in children); fat redistribution; drug interactions; perform baseline and periodic monitoring of liver function tests, complete blood counts, and CD4+ counts. |
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| Lamivudine, nevirapine, and zidovudine are FDA Pregnancy Category C. Lamivudine and zidovudine cross the placenta, with fetal concentrations similar to maternal. Nevirapine also crosses the placenta. Zidovudine has been associated with a risk of mitochondrial dysfunction in infants with in utero exposure, but generally, the combination is used to prevent mother-to-child transmission of HIV. First trimester: limited data; theoretical risk of teratogenicity based on animal studies. Second and third trimesters: use is indicated for prevention of vertical transmission; no strong evidence of structural teratogenicity, but zidovudine may be associated with transient hematologic abnormalities in neonates (anemia, neutropenia). Long-term effects unclear. |
| Fetal Monitoring | Monitor maternal CD4 count, HIV viral load, liver function tests (especially for nevirapine-induced hepatotoxicity), complete blood count (for zidovudine-related anemia/neutropenia), and renal function. Fetal monitoring includes ultrasound for growth and well-being, and neonatal hematologic monitoring (CBC) at birth. Assess for signs of nevirapine-associated rash or hypersensitivity. |
| Fertility Effects | No known clinically significant effects on fertility. HIV itself may affect fertility; antiretroviral therapy may improve general health and fertility. No specific impairment from lamivudine, nevirapine, or zidovudine in animal studies. Human data limited. |