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). |
| Molecular Weight | Lamivudine: 229.26 Da; Zidovudine: 267.24 Da |
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 | Use only if benefit outweighs risk; associated with mitochondrial toxicity and lactic acidosis in pregnancy. |
| 2nd trimester | May be used; monitor for lactic acidosis and hepatic steatosis. |
| 3rd trimester | May be used; available data do not show increased risk of major birth defects. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
| FDA category | Human |
| Placental transfer | Both lamivudine and zidovudine readily cross the placenta; placental transfer is well-documented with ratios approaching 1. |
| Breastfeeding | Both drugs are excreted into human milk. Zidovudine concentrations in milk are similar to maternal plasma; lamivudine reaches higher levels. Potential for viral resistance and adverse effects in infant. In the US, guidelines recommend avoiding breastfeeding for HIV-positive mothers. |
■ 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 or zidovudineNeutropenia (absolute neutrophil count < 750/mm3)Anemia (hemoglobin < 7.5 g/dL or > 25% decrease from baseline)Lactation (in settings where formula is available) – per US guidelines
| 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 |
| Food/Dietary |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | 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. |
| No significant food interactions. May be taken with or without food. Avoid excessive alcohol due to risk of lactic acidosis and pancreatitis. |
| Clinical Pearls | Monitor CBC with differential and platelets every 2 weeks for first 3 months, then monthly thereafter due to risk of neutropenia and anemia. Screen for HLA-B*5701 before abacavir use if switching from ZDV; not applicable here. Lamivudine + zidovudine is a dual NRTI backbone, but avoid in patients with cirrhosis due to increased risk of hepatotoxicity. Check renal function; reduce zidovudine dose in CrCl <15 mL/min. Watch for lactic acidosis with hepatic steatosis, especially in obese patients or those on prolonged therapy. |
| Patient Advice | Take this medication exactly as prescribed, usually twice daily with or without food. · Do not miss doses; skipping increases risk of viral resistance and treatment failure. · Common side effects include nausea, headache, and fatigue; these may improve over time. · Report any signs of anemia (pale skin, unusual tiredness) or infection (fever, sore throat) immediately. · This combination does not cure HIV and can still transmit the virus; use condoms and practice safe sex. |