LAMIVUDINE, ZIDOVUDINE TABS 150MG/300MG CO-PACKAGED WITH NEVIRAPINE TABS 200MG
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 via DNA chain termination after intracellular phosphorylation to lamivudine triphosphate. Zidovudine is also an NRTI that inhibits HIV reverse transcriptase after phosphorylation to zidovudine triphosphate. Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to reverse transcriptase, causing enzyme inhibition.
| Metabolism | Lamivudine is extensively metabolized by intracellular phosphorylation to the active triphosphate; limited hepatic metabolism via CYP enzymes. Zidovudine is primarily metabolized via glucuronidation by UGT2B7 to an inactive metabolite; also undergoes intracellular phosphorylation. Nevirapine is primarily metabolized by CYP3A4 and CYP2B6 to hydroxylated metabolites. |
| Excretion | Lamivudine: ~70% renal (glomerular filtration and active tubular secretion) as unchanged drug; ~30% metabolized to inactive metabolites (trans-sulfoxide) excreted renally. Zidovudine: ~75% renal (metabolite zidovudine-glucuronide) and ~20% unchanged; ~5% fecal. Nevirapine: ~80% renal (metabolites, mainly 2-hydroxy- and 3-hydroxy-nevirapine glucuronides), ~10% fecal, <5% unchanged. |
| Half-life | Lamivudine: 5-7 hours (terminal half-life); prolonged to ~10-15 hours in advanced HIV infection; increased with renal impairment. Zidovudine: 0.5-3 hours (mean ~1 hour); prolonged to ~1.5-3 hours in renal impairment; intracellular active metabolite zidovudine-triphosphate has half-life ~3-7 hours. Nevirapine: ~25-30 hours (single dose), ~40-60 hours with multiple dosing (autoinduction reduces to ~20-30 hours after 2-4 weeks). |
| Protein binding | Lamivudine: 16-36% (minimal, mainly albumin). Zidovudine: 30-38% (primarily albumin). Nevirapine: ~60% (primarily albumin); binding is not affected by renal or hepatic impairment. |
| Volume of Distribution | Lamivudine: 1.3 L/kg (range 0.9-1.8 L/kg); distributes widely into tissues, mean Vd ~ 90 L for 70 kg adult. Zidovudine: 1.4 L/kg (range 1.0-2.0 L/kg); Vd ~ 100 L for 70 kg adult; penetrates CNS (CSF:plasma ratio ~0.5). Nevirapine: 1.2 L/kg (range 0.8-1.5 L/kg); Vd ~ 85 L for 70 kg adult; distributes into breast milk (60% maternal plasma) and crosses placenta. |
| Bioavailability | Lamivudine: Oral: ~86% (range 80-88%); no significant food effect. Zidovudine: Oral: ~65% (range 52-75%); food reduces Cmax but not AUC. Nevirapine: Oral: >90% (range 85-96%); no significant food effect; bioequivalent between tablet and oral suspension (tablet dissolved in water is acceptable). |
| Onset of Action | Lamivudine: Oral - antiviral effect begins within 1-2 hours (inhibition of reverse transcriptase). Zidovudine: Oral - antiviral effect begins within 1-2 hours. Nevirapine: Oral - antiviral effect begins within 2-4 hours (peak plasma concentration at 4 hours). For all: clinical improvement (e.g., CD4 increase, viral load reduction) typically observed within 2-4 weeks. |
| Duration of Action | Lamivudine: Dosing interval 12 hours (twice daily) due to half-life; intracellular triphosphate half-life ~10.5-15.5 hours supports q12h dosing. Zidovudine: Dosing interval 12 hours (twice daily) despite short half-life due to intracellular triphosphate half-life ~3-7 hours; clinical suppression maintained with q12h. Nevirapine: Dosing interval 12 hours (twice daily) after initial 2-week lead-in of once daily; long half-life allows q12h maintenance; autoinduction may reduce duration of action over time. |
One tablet of lamivudine/zidovudine (150 mg/300 mg) orally twice daily. One tablet of nevirapine (200 mg) orally once daily for 14 days, then one tablet twice daily thereafter.
| Dosage form | TABLET |
| Renal impairment | For lamivudine/zidovudine: Avoid if creatinine clearance <50 mL/min; consider separate formulations. For nevirapine: No dose adjustment required for renal impairment; not removed by dialysis. |
| Liver impairment | For nevirapine: Contraindicated in Child-Pugh class B or C. For lamivudine: No adjustment for mild impairment; no data for severe. For zidovudine: Reduce dose in advanced cirrhosis (e.g., 300 mg every 12 hours). |
| Pediatric use | Not applicable as fixed-dose combination tablets are not recommended for children <12 years. Use individual weight-based dosing: lamivudine 4 mg/kg twice daily, zidovudine 240 mg/m2 every 12 hours, nevirapine 150 mg/m2 once daily for 14 days then twice daily. |
| Geriatric use | Monitor renal function closely; adjust lamivudine/zidovudine dose based on creatinine clearance. Nevirapine: no specific adjustment, but monitor for hepatotoxicity and rash. |
| 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: Excreted into human milk; M/P ratio 0.6-3.3. Zidovudine: Excreted into human milk; M/P ratio 0.8-1.1. Nevirapine: Excreted into human milk; M/P ratio ~0.5. Breastfeeding contraindicated in HIV infection to avoid transmission; in HIV-negative mothers, limited data suggest low risk, but use caution. |
| Teratogenic Risk |
■ FDA Black Box Warning
Hematologic toxicity, including neutropenia and severe anemia, has been associated with zidovudine. Prolonged use has been associated with symptomatic myopathy. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues. Nevirapine can cause severe, life-threatening hepatotoxicity and skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), especially in the first 18 weeks of therapy. Patients with higher CD4 counts at initiation of nevirapine are at increased risk of hepatotoxicity.
| Common Effects | Anemia |
| Serious Effects |
Hypersensitivity to lamivudine, zidovudine, or nevirapine. Concomitant use with rifampin, St. John's wort, or other NNRTIs. Severe hepatic impairment (Child-Pugh class B or C) for nevirapine. Severe anemia (hemoglobin <7.5 g/dL) or neutropenia (<750 cells/mm³) for zidovudine.
| Precautions | Monitor hematologic parameters (especially with zidovudine) due to risk of neutropenia and anemia. Monitor hepatic function and signs of hepatotoxicity (nevirapine). Monitor for lactic acidosis and severe hepatomegaly with steatosis (nucleoside analogues). Monitor for skin reactions (nevirapine). Do not use nevirapine as part of post-exposure prophylaxis. Adjust dose in renal impairment (lamivudine and zidovudine). Caution in hepatic impairment. Immune reconstitution syndrome may occur. Drug interactions: nevirapine induces CYP3A4, reducing levels of co-administered drugs metabolized by this enzyme. |
Loading safety data…
| Lamivudine/zidovudine: Pregnancy category C. First trimester: No increase in birth defects in prospective studies, but animal studies show risk. Second/third trimester: No evidence of fetal harm in humans; toxicity may include mitochondrial dysfunction in neonates. Nevirapine: Pregnancy category B. First trimester: No embryotoxicity in animal studies; limited human data. Second/third trimester: Increased risk of hepatotoxicity in pregnant women. Overall, combination may reduce perinatal HIV transmission but requires risk-benefit assessment. |
| Fetal Monitoring | Maternal: Complete blood count, liver function tests at baseline and periodically; monitor for hepatotoxicity with nevirapine (especially during first 18 weeks). Fetal: Ultrasound for growth and anatomy; neonatal monitoring for anemia, neutropenia, and mitochondrial dysfunction; HIV testing per protocol. |
| Fertility Effects | No known significant adverse effects on fertility in humans; animal studies show no impairment with lamivudine/zidovudine; nevirapine did not affect fertility in animal studies. |