LAMIVUDINE AND ZIDOVUDINE
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, causing chain termination. Both drugs act synergistically.
| Metabolism | Lamivudine is minimally metabolized (5-10%) via hepatic glucuronidation; primarily excreted unchanged in urine. Zidovudine is extensively metabolized via hepatic glucuronidation to zidovudine glucuronide; also undergoes minor metabolism to 3'-amino-3'-deoxythymidine. Both are substrates of renal organic cation transporters. |
| Excretion | Lamivudine: ~70% unchanged in urine via active tubular secretion; Zidovudine: ~75% as metabolites (primarily 5'-glucuronide, G-ZDV) and ~15% unchanged in urine via glomerular filtration and tubular secretion. |
| Half-life | Lamivudine: 5-7 hours (mean 5.5 h); Zidovudine: 0.5-3 hours (mean ~1 h). In renal impairment, half-life of both prolonged; terminal phase reflects slow elimination from intracellular active triphosphates. |
| Protein binding | Lamivudine: <36% bound to plasma albumin; Zidovudine: ~34-38% bound to plasma albumin. |
| Volume of Distribution | Lamivudine: 1.3 L/kg (pregnant women higher), indicating distribution into total body water; Zidovudine: 1.6 L/kg, crosses blood-brain barrier and into CSF. |
| Bioavailability | Lamivudine: oral bioavailability 86-88%; Zidovudine: oral bioavailability ~60-70% (varies with food; reduced by ~22% with high-fat meal but clinical significance minimal). |
| Onset of Action | Oral: Antiretroviral effect begins within hours, but maximum virological suppression achieved over 2-4 weeks with compliance. |
| Duration of Action | Dosing interval 12 hours; intracellular active triphosphate of lamivudine persists 12-24 hours; zidovudine triphosphate t1/2 ~3-4 hours. Clinical effect requires sustained dosing; viral rebound occurs if doses missed. |
One tablet (lamivudine 150 mg / zidovudine 300 mg) orally twice daily.
| Dosage form | TABLET |
| Renal impairment | If CrCl 15–49 mL/min: lamivudine reduced to 150 mg once daily; zidovudine standard dose. If CrCl <15 mL/min or on hemodialysis: not recommended; use individual components. |
| Liver impairment | No specific dose adjustment for lamivudine; zidovudine contraindicated in Child-Pugh C. Use with caution in Child-Pugh A/B; consider dose reduction of zidovudine (e.g., 300 mg once daily or 100 mg three times daily). |
| Pediatric use | Children ≥12 years and ≥30 kg: 1 tablet (150/300 mg) orally twice daily. For younger children or those <30 kg, use individual components based on weight: lamivudine 4 mg/kg twice daily (max 150 mg), zidovudine 8 mg/kg twice daily (max 300 mg). |
| Geriatric use | Caution due to age-related renal decline; monitor renal function and adjust dose accordingly. No specific dose changes for age alone. |
| 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 in human milk. M/P ratio not well-defined. In HIV-infected women, breastfeeding is contraindicated to prevent postnatal transmission. In HBV-infected women, risk-benefit ratio should be considered. |
| Teratogenic Risk | First trimester: No increased risk of major birth defects based on data from Antiretroviral Pregnancy Registry. Second/third trimester: No observed fetal toxicity; used in combination therapy for HIV treatment and prevention of perinatal transmission. |
■ FDA Black Box Warning
Hematologic toxicity, including neutropenia and severe anemia, especially in patients with advanced HIV disease. Also, prolonged use may be associated with myopathy. Risk of lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, particularly in women, obesity, and prolonged nucleoside exposure. Exacerbation of hepatitis B virus (HBV) infection upon discontinuation in patients co-infected with HBV and HIV.
| Common Effects | Anemia |
| Serious Effects |
Hypersensitivity to lamivudine or zidovudine. Do not use with other lamivudine- or zidovudine-containing products, emtricitabine, or zalcitabine. Not for treatment of HBV monoinfection.
| Precautions | Hematologic toxicity (anemia, neutropenia), monitor CBC frequently. Lactic acidosis and hepatomegaly with steatosis. Exacerbation of HBV after discontinuation in co-infected patients. Immune reconstitution syndrome. Fat redistribution. Bone marrow suppression. Pancreatitis in pediatric patients. Drug interactions (e.g., ribavirin, ganciclovir). |
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| Fetal Monitoring | Maternal: Complete blood count (CBC) with differential every 2-4 weeks, hepatic function, renal function, LDH, and electrolytes. Monitor for anemia, neutropenia, and thrombocytopenia. Fetal: Ultrasound for growth and anatomy; consider fetal echocardiogram due to possible mitochondrial toxicity. |
| Fertility Effects | No evidence of impaired fertility in animal studies. In humans, limited data suggest no significant effect on male or female fertility. Lamivudine and zidovudine may contribute to successful pregnancy outcomes by controlling HIV or HBV replication. |