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. |
| 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 | 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 | Use during first trimester only if clearly needed; associated with mitochondrial toxicity and lactic acidosis; pregnancy category C. |
| 2nd trimester | Limited data but considered safer than first trimester; monitor for anemia and hepatic steatosis. |
| 3rd trimester | Generally considered safe; used to prevent mother-to-child transmission (PMTCT); monitor for hematologic toxicity. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and myopathy.
| FDA category | Human |
| Placental transfer | Both drugs cross the placenta; zidovudine achieves cord blood concentrations similar to maternal; lamivudine placental transfer ratio ~1.0. |
| Breastfeeding |
■ 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 zidovudineNeutropenia (ANC < 750/mm3)Severe anemia (hemoglobin < 7.5 g/dL)
| 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). |
Loading safety data…
| Both lamivudine and zidovudine are excreted into breast milk in low concentrations; limited safety data; avoid breastfeeding in HIV-positive women where formula is available and acceptable to prevent postnatal transmission. |
| Lactation Rating | L4 (Hazardous) |
| 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. |
| 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. |
| Food/Dietary |
| No significant food interactions. May be taken with or without food. Grapefruit juice does not affect lamivudine or zidovudine. |
| Clinical Pearls | Monitor for hematologic toxicity (anemia, neutropenia) especially in advanced HIV disease. Avoid in patients with creatinine clearance <50 mL/min. Lactic acidosis with hepatic steatosis is a rare but serious adverse effect. Not recommended for use in pregnancy due to potential harm to fetus (zidovudine link to mitochondrial toxicity). |
| Patient Advice | Take this medication exactly as prescribed, usually twice daily with or without food. · Do not share your medication with others; it is not a cure for HIV and may still transmit the virus. · Report any signs of anemia (pale skin, fatigue, shortness of breath) or neutropenia (fever, chills, sore throat) immediately. · Seek medical help if you experience unexplained muscle pain, abdominal pain, or yellowing of eyes/skin (signs of lactic acidosis/liver problems). · Use effective barrier contraception to prevent HIV transmission to others. · Do not breastfeed while taking this medication; HIV can be passed to the baby. |