LAMIVUDINE; 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); tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor (NtRTI). Both inhibit HIV-1 reverse transcriptase and hepatitis B virus polymerase, causing chain termination of viral DNA.
| Metabolism | Lamivudine is not significantly metabolized; tenofovir disoproxil fumarate is metabolized to tenofovir by hydrolysis, and tenofovir is not significantly metabolized by CYP450 enzymes. |
| Excretion | Lamivudine: predominantly renal (~70% unchanged). Tenofovir: renal (~70-80% unchanged via glomerular filtration and active tubular secretion). |
| Half-life | Lamivudine: 5-7 hours (healthy), up to 13.1 hours (moderate renal impairment). Tenofovir: 17-25 hours (HIV), 32-49 hours (hepatitis B), prolonged in renal impairment. |
| Protein binding | Lamivudine: <36% (albumin). Tenofovir: <7.2% (albumin). |
| Volume of Distribution | Lamivudine: 1.3 L/kg (total body water). Tenofovir: 1.2-1.3 L/kg (extracellular fluid). |
| Bioavailability | Oral: Lamivudine 80-88%; tenofovir disoproxil fumarate 25% (under fasting conditions), increased 40% with high-fat meal. |
| Onset of Action | Oral: Lamivudine peak plasma levels 0.5-2 hours; tenofovir 1-2 hours. Clinical antiviral effect within days to weeks. |
| Duration of Action | Dosing interval 24 hours due to intracellular active metabolites (lamivudine triphosphate, tenofovir diphosphate) with long intracellular half-lives (lamivudine 15-19 hours; tenofovir >60 hours). |
One tablet (300 mg tenofovir disoproxil fumarate and 300 mg lamivudine) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Not recommended for patients with CrCl < 30 mL/min. For CrCl 30-49 mL/min: administer one tablet every 48 hours. For CrCl 50-79 mL/min: no dosage adjustment required. For CrCl >= 80 mL/min: no adjustment. |
| Liver impairment | Lamivudine: No adjustment required for mild to moderate hepatic impairment. For severe hepatic impairment (Child-Pugh C), reduce lamivudine dose to 25 mg daily. Tenofovir disoproxil fumarate: No dose adjustment required for hepatic impairment. |
| Pediatric use | Approved for patients weighing >= 35 kg: one tablet (tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg) orally once daily. For patients < 35 kg, individual components should be used based on weight. |
| Geriatric use | Select dose with caution due to age-related renal impairment. Monitor renal function and adjust dose according to creatinine clearance. |
| 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 human breast milk; M/P ratio for lamivudine ~3.3, for tenofovir ~1.0. Guidelines recommend avoiding breastfeeding in HIV+ mothers in high-resource settings due to transmission risk; in low-resource settings, exclusive breastfeeding with maternal ART may be recommended. For HBV, breastfeeding not contraindicated. |
| Teratogenic Risk |
■ FDA Black Box Warning
Post treatment acute exacerbation of hepatitis B; HIV resistance in monotherapy; lactic acidosis and severe hepatomegaly with steatosis.
| Common Effects | Hepatitis B |
| Serious Effects |
Hypersensitivity to any component; coadministration with drugs containing lamivudine or tenofovir disoproxil fumarate (e.g., emtricitabine/tenofovir) due to similar components; not recommended in patients with creatinine clearance < 30 mL/min.
| Precautions | Lactic acidosis and hepatomegaly with steatosis; renal impairment; bone mineral density reduction; immune reconstitution syndrome; HBV exacerbation upon discontinuation; pancreatitis (lamivudine). |
Loading safety data…
| No increased risk of major birth defects observed in first trimester; use throughout pregnancy recommended for HIV/HBV treatment. Animal studies show no evidence of teratogenicity. For exposure during first trimester, data from >6000 women show no increased malformation risk. |
| Fetal Monitoring | Monitor maternal renal function (serum creatinine, urine protein) and hepatic function monthly; fetal growth ultrasound every trimester; HIV viral load and CD4 count (if HIV) every 1-3 months; HBV DNA and LFTs (if HBV) every 3 months. Assess for anemia (CBC) periodically. |
| Fertility Effects | No known negative impact on fertility in human studies. Animal studies show no impairment of fertility at clinically relevant doses. Used safely in pregnant women requiring ART. |