LAMIVUDINE; 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). Zidovudine is a thymidine analog, and lamivudine is a cytidine analog. They are phosphorylated to active triphosphate metabolites that competitively inhibit HIV reverse transcriptase and cause chain termination of viral DNA synthesis.
| Metabolism | Zidovudine is metabolized primarily by glucuronidation (UGT2B7) to 3'-azido-3'-deoxy-5'-O-β-D-glucopyranuronosylthymidine (GAZT); lamivudine undergoes minimal hepatic metabolism and is predominantly excreted unchanged in urine via active tubular secretion (OCT2 and MATE1). |
| Excretion | Lamivudine: Renal (70% unchanged). Zidovudine: Renal (14% unchanged), metabolism to GAZT (glucuronide) excreted renally. |
| Half-life | Lamivudine: 5-7 hours (prolonged in renal impairment). Zidovudine: 0.5-3 hours (intracellular triphosphate half-life 3-7 hours). |
| Protein binding | Lamivudine: <36% (plasma albumin). Zidovudine: 34-38% (albumin). |
| Volume of Distribution | Lamivudine: 1.3 L/kg (distributes widely including CSF). Zidovudine: 1.6 L/kg (including CNS). |
| Bioavailability | Lamivudine: 80% oral. Zidovudine: 60-70% oral. |
| Onset of Action | Oral: Antiretroviral effect begins within 1-2 weeks (time to viral load reduction). |
| Duration of Action | 12 hours (dosing every 12 hours); intracellular triphosphate persists longer (24-48 hours). |
One tablet (lamivudine 150 mg / zidovudine 300 mg) orally twice daily.
| Dosage form | TABLET |
| Renal impairment | For CrCl ≥30 mL/min: No adjustment needed. For CrCl <30 mL/min: Use individual components; avoid fixed-dose combination. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B or C: Dose reduction of zidovudine may be required; use individual components with monitoring. |
| Pediatric use | Weight-based dosing: For children ≥12 years and ≥30 kg: one tablet (150/300 mg) twice daily. For children <12 years or <30 kg: Use individual components per weight-based guidelines (zidovudine 240 mg/m2 or 8 mg/kg twice daily; lamivudine 4 mg/kg twice daily). |
| Geriatric use | No specific dose adjustments based on age alone; monitor renal function and adjust doses accordingly due to age-related decline in CrCl. |
| 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. Lamivudine M/P ratio is approximately 3.3; zidovudine M/P ratio is about 0.2-1.0. Because of the risk of HIV transmission via breastfeeding, HIV-infected women should not breastfeed. In non-HIV conditions, caution is advised; consider infant monitoring for toxicity (e.g., anemia, neutropenia). |
| Teratogenic Risk |
■ FDA Black Box Warning
Hematologic toxicity including neutropenia and anemia, especially in patients with advanced HIV disease; prolonged use associated with symptomatic myopathy and myositis (zidovudine); lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal; risk of fatal pancreatitis in pediatric patients (lamivudine).
| Common Effects | Anemia |
| Serious Effects |
["Hypersensitivity to lamivudine, zidovudine, or any component of the formulation","Neutrophil count < 750/mm³ or hemoglobin < 7.5 g/dL (relative)","Use with other zidovudine-containing products","Co-administration with anticancer agents (e.g., ribavirin) due to increased hepatotoxicity risk"]
| Precautions | ["Hematologic toxicity (monitor CBC frequently)","Lactic acidosis and hepatomegaly with steatosis","Pancreatitis (especially in pediatric patients)","Myopathy","Lipodystrophy and immune reconstitution syndrome","Bone marrow suppression","Use with caution in hepatic impairment"] |
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| Lamivudine and zidovudine cross the placenta. Zidovudine is associated with a low risk of teratogenicity; human data show no increased risk of major malformations. Lamivudine has limited data but no clear teratogenic signal. Both agents are used in pregnancy for prevention of perinatal HIV transmission. First trimester: no evidence of major teratogenicity. Second/third trimesters: continued use recommended; potential for hematologic toxicity (anemia, neutropenia) in neonates, which is typically reversible. |
| Fetal Monitoring | Maternal: CBC with differential, liver function tests, renal function, and HIV RNA levels (if used for HIV). Fetal/neonatal: Monitor for anemia, neutropenia; check cord blood hematologic parameters at birth. Consider growth ultrasound and fetal monitoring per standard obstetric care. |
| Fertility Effects | No known significant adverse effects on fertility in humans. Animal studies with lamivudine showed no impairment of fertility; zidovudine had no effect on fertility in rats. Data in humans are limited but no evidence of reduced fertility. |