LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that is phosphorylated to its active metabolite, lamivudine triphosphate, which inhibits HIV-1 reverse transcriptase by competing with natural substrate and causing chain termination. Tenofovir disoproxil fumarate is a nucleotide analogue, tenofovir, which after diphosphorylation inhibits HIV-1 reverse transcriptase and hepatitis B virus polymerase via DNA chain termination.
| Metabolism | Lamivudine is primarily eliminated by renal excretion of unchanged drug (approximately 70%) via active tubular secretion and glomerular filtration. Tenofovir disoproxil fumarate is converted to tenofovir by esterases; tenofovir undergoes renal elimination via glomerular filtration and active tubular secretion. |
| Excretion | Renal: Lamivudine ~70% unchanged; Tenofovir ~70-80% unchanged via glomerular filtration and active tubular secretion. |
| Half-life | Lamivudine: 5-7 hours intracellular triphosphate 10.5-15.5 hours. Tenofovir: 17 hours (pro-drug) intracellular active diphosphate >60 hours. Once daily dosing maintains therapeutic concentrations. |
| Protein binding | Lamivudine: <36% (human serum albumin). Tenofovir: <7% (minimal binding). |
| Volume of Distribution | Lamivudine: ~1.3 L/kg (widespread total body water). Tenofovir: ~1.2 L/kg (extensive extravascular distribution including kidneys and lymphoid tissue). |
| Bioavailability | Lamivudine: 86% (oral). Tenofovir disoproxil fumarate: 25% (oral, enhanced with high-fat meal ~40%). |
| Onset of Action | Oral: Lamivudine and Tenofovir - pharmacokinetic steady state within 5-7 days; antiviral effect measurable within 2-4 weeks. |
| Duration of Action | Lamivudine: 24 hours (once daily). Tenofovir: >24 hours (once daily). Clinical suppression of HIV/HBV requires continuous adherence. |
One tablet orally once daily, each tablet containing lamivudine 300 mg and tenofovir disoproxil fumarate (equivalent to tenofovir disoproxil 245 mg or tenofovir 300 mg).
| Dosage form | TABLET |
| Renal impairment | For CrCl ≥50 mL/min: no adjustment. For CrCl 30–49 mL/min: one tablet every 48 hours. For CrCl 10–29 mL/min: one tablet every 72–96 hours. For CrCl <10 mL/min or hemodialysis: not recommended due to inadequate dosing data (use individual components if necessary, tenofovir DF q7 days, lamivudine single doses based on CrCl). |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). No data in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | For children weighing ≥35 kg and ≥12 years old: one tablet (lamivudine 300 mg / tenofovir DF 300 mg) orally once daily. For children 2 to <12 years and/or weight <35 kg: use individual components (lamivudine weight-based dose 8 mg/kg/day up to 300 mg, tenofovir DF 300 mg once daily if ≥35 kg; for <35 kg, tenofovir DF dose not established for this combination). |
| Geriatric use | Select dose with caution, monitor renal function; consider age-related decline in CrCl; follow renal adjustment guidelines based on CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Breastfeeding | Both lamivudine and tenofovir are excreted into breast milk. Lamivudine M/P ratio ~3.3; tenofovir M/P ratio ~0.9. Avoid breastfeeding if replacement feeding is acceptable; otherwise, consider benefits vs. risk. |
| Teratogenic Risk | Lamivudine: No increased risk of birth defects in first trimester based on Antiretroviral Pregnancy Registry data. Tenofovir disoproxil fumarate: No evidence of teratogenicity in humans; animal studies show no fetal harm. Overall, risk not increased above background. |
■ FDA Black Box Warning
Posttreatment exacerbation of hepatitis B: Severe acute exacerbations of HBV have been reported in patients co-infected with HIV-1 and HBV who have discontinued lamivudine and/or tenofovir disoproxil fumarate. Monitor hepatic function closely in these patients.
| Common Effects | Hepatitis B |
| Serious Effects |
["Hypersensitivity to any component of the product"]
| Precautions | ["Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of nucleoside analogues alone or in combination, including lamivudine and tenofovir","Exacerbation of hepatitis B upon discontinuation","New onset or worsening renal impairment; monitor creatinine clearance","Decreased bone mineral density; potential for fractures","Immune reconstitution syndrome","Fat redistribution","Pancreatitis (especially in pediatric patients)"] |
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| Fetal Monitoring | Monitor maternal liver function, renal function (serum creatinine, urine protein), and viral load. Fetal ultrasound for growth assessment. Monitor for anemia and neutropenia in infant. |
| Fertility Effects | No known adverse effects on fertility in males or females based on available data. Antiretroviral therapy may improve fertility by reducing viral load. |