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). |
| Molecular Weight | Lamivudine: 229.3 Da; Tenofovir disoproxil fumarate: 635.5 Da (as the salt), 519.4 Da (free base) |
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 | Lamivudine: Human data suggest low risk of malformations; maternal toxicity at high doses in animals. Tenofovir disoproxil fumarate: Human data do not show increased risk of major birth defects; animal studies show no evidence of teratogenicity at clinically relevant doses. |
| 2nd trimester | Both drugs are considered safe for use during pregnancy based on human data from the Antiretroviral Pregnancy Registry. No increased risk of adverse fetal outcomes. |
| 3rd trimester | Use throughout pregnancy is recommended for HIV treatment; may reduce risk of mother-to-child transmission. Tenofovir is associated with mild reductions in bone mineral density in infants, but clinical significance unclear. |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Placental transfer | Both drugs cross the human placenta. Lamivudine: AUC cord blood/maternal blood ratio ~0.5-1.0. Tenofovir: Ratio ~0.6-1.0, with active transport by placental efflux transporters. |
■ 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 lamivudine, tenofovir, or any component of the formulation
| Precautions | Lactic acidosis and hepatomegaly with steatosis; renal impairment; bone mineral density reduction; immune reconstitution syndrome; HBV exacerbation upon discontinuation; pancreatitis (lamivudine). |
| Food/Dietary | No significant food interactions; can be taken with or without food. High-fat meals do not affect absorption significantly. Avoid alcohol as it may worsen liver effects and increase risk of lactic acidosis. Maintain adequate hydration. |
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| Breastfeeding | Lamivudine and tenofovir are excreted into human breast milk in low concentrations. In HIV-infected mothers, breastfeeding is not recommended due to risk of HIV transmission. In hepatitis B, benefits may outweigh risks; infant exposure is minimal but data on long-term effects are limited. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | 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. |
| Clinical Pearls | Monitor renal function (serum creatinine, eGFR, urinalysis) at baseline and regularly during therapy due to risk of nephrotoxicity. Check HIV/HBV co-infection status before initiating; lamivudine has activity against HBV, and discontinuation may cause severe HBV flares. Use with caution in patients with hepatic impairment (Child-Pugh class B or C) due to increased lamivudine exposure. Tenofovir disoproxil fumarate is associated with decreased bone mineral density; consider DEXA scan in patients with risk factors for bone loss. Monitor for lactic acidosis and hepatomegaly with steatosis, although more common with nucleoside analogs. Dose adjustment of tenofovir is required if CrCl <50 mL/min; fixed-dose combination tablets should not be used if CrCl <30 mL/min. |
| Patient Advice | Take this medication exactly as prescribed, typically once daily with or without food. · Do not miss doses; if you miss a dose, take it as soon as you remember unless it is almost time for the next dose. Do not double the dose. · This medication does not cure HIV or AIDS, nor does it prevent transmission to others; continue to practice safe sex and avoid sharing needles. · Report symptoms of lactic acidosis (unusual tiredness, muscle pain, stomach pain with nausea or vomiting, fast or irregular heartbeat) or liver problems (dark urine, jaundice, severe nausea, upper right stomach area pain) immediately. · Regular blood tests (kidney function, liver function, HIV viral load) are required during treatment. · Do not stop this medication without consulting your doctor, especially if you have hepatitis B, as stopping lamivudine can cause severe hepatitis flares. · If you are pregnant, planning pregnancy, or breastfeeding, discuss the risks and benefits with your healthcare provider. · Take all other prescribed HIV medications as directed; do not change your regimen without medical advice. |