EMTRICITABINE; TENOFOVIR DISOPROXIL FUMARATE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) that is phosphorylated to its active metabolite, which competes with the natural substrate deoxycytidine 5'-triphosphate and incorporates into viral DNA, causing chain termination. Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor (NtRTI) that is converted to tenofovir, which is phosphorylated to tenofovir diphosphate and competes with deoxyadenosine 5'-triphosphate, resulting in DNA chain termination. Both inhibit HIV-1 reverse transcriptase.
| Metabolism | Emtricitabine is minimally metabolized by oxidation and glucuronidation; it is not a substrate of CYP450 enzymes. Tenofovir disoproxil fumarate is metabolized by hydrolysis to tenofovir; tenofovir undergoes limited metabolism via phosphorylation to its active form and is not metabolized by CYP450 enzymes. |
| Excretion | Emtricitabine: 86% renal (glomerular filtration and active tubular secretion), 14% fecal; Tenofovir: 70-80% renal (glomerular filtration and active tubular secretion) as unchanged drug, remainder metabolized and excreted renally. |
| Half-life | Emtricitabine: 10 hours (increased to 20-30 hours in renal impairment); Tenofovir: 17 hours (prolonged to 30-50 hours in renal impairment). |
| Protein binding | Emtricitabine: <4% bound to plasma proteins; Tenofovir: <0.7% bound to plasma proteins. |
| Volume of Distribution | Emtricitabine: 1.4 L/kg (distributes into total body water); Tenofovir: 0.8-1.2 L/kg (distributes into extravascular tissues). |
| Bioavailability | Emtricitabine: 93% oral; Tenofovir disoproxil fumarate: 25% oral (increases to 39% with high-fat meal). |
| Onset of Action | Oral: Antiviral effect begins within hours, but clinical reduction in viral load measurable after 1-2 weeks of therapy. |
| Duration of Action | Oral: Dosing interval every 24 hours maintains therapeutic concentrations; viral suppression requires continuous daily dosing. |
One tablet (emtricitabine 200 mg / tenofovir disoproxil fumarate 300 mg) orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl ≥30 mL/min: No adjustment. CrCl 15-29 mL/min: Administer one tablet every 48 hours. CrCl <15 mL/min or on hemodialysis: Not recommended (or use a renally adjusted formulation if available; data insufficient for dosing recommendation). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | For children weighing ≥35 kg: One tablet (200 mg emtricitabine / 300 mg tenofovir disoproxil fumarate) orally once daily. For children 17 to <35 kg: Not recommended as tablet is a fixed-dose combination not appropriate for weight-based dosing; use individual components. |
| Geriatric use | No specific dose adjustment based on age alone. Monitor renal function closely due to age-related decline in CrCl and adjust dose accordingly per renal adjustment guidelines. |
| 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 | Emtricitabine is excreted into human milk at low levels (M/P ratio approximately 0.5-0.8). Tenofovir is excreted into human milk in low amounts (M/P ratio approximately 0.2-0.5). The American Academy of Pediatrics considers emtricitabine and tenofovir compatible with breastfeeding. However, caution is advised in HIV-positive women to avoid transmission; WHO recommends exclusive breastfeeding for HIV-positive mothers on ART. |
| Teratogenic Risk |
■ FDA Black Box Warning
WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs. Severe acute exacerbations of hepatitis B have been reported in patients co-infected with HIV-1 and hepatitis B virus (HBV) who have discontinued emtricitabine or tenofovir disoproxil fumarate. Hepatic function should be monitored closely in these patients.
| Common Effects | Hepatitis B |
| Serious Effects |
["Hypersensitivity to emtricitabine, tenofovir disoproxil fumarate, or any component of the formulation","Concomitant use with other drugs containing emtricitabine, tenofovir disoproxil fumarate, or tenofovir alafenamide","Concomitant use of adefovir dipivoxil (for tenofovir component)"]
| Precautions | ["Lactic acidosis and severe hepatomegaly with steatosis","Exacerbation of hepatitis B upon discontinuation (in HBV co-infected patients)","New onset or worsening renal impairment; monitor renal function","Decreased bone mineral density","Immune reconstitution syndrome","Fat redistribution"] |
Loading safety data…
| Emtricitabine and tenofovir disoproxil fumarate are FDA Pregnancy Category B. No increased risk of major birth defects has been observed in human studies. First trimester: No evidence of teratogenicity. Second/third trimester: No fetal toxicity reported. However, cases of lactic acidosis and hepatic steatosis have been reported in pregnant women receiving nucleoside analogues. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function (serum creatinine, estimated creatinine clearance), and urine protein. Assess for lactic acidosis and hepatic steatosis. Monitor HIV viral load and CD4 count. Fetal monitoring includes standard prenatal ultrasound; no specific fetal monitoring required beyond routine care. |
| Fertility Effects | No significant adverse effects on fertility have been reported in animal studies. Human data are insufficient. Emtricitabine and tenofovir do not appear to impair male or female fertility. |