ODEFSEY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ODEFSEY (ODEFSEY).
ODEFSEY is a fixed-dose combination of emtricitabine (nucleoside reverse transcriptase inhibitor, NRTI) and rilpivirine (non-nucleoside reverse transcriptase inhibitor, NNRTI). Emtricitabine is phosphorylated to its active triphosphate form, which competes with deoxycytidine triphosphate for incorporation into viral DNA, resulting in chain termination. Rilpivirine binds to reverse transcriptase and inhibits RNA-dependent and DNA-dependent DNA polymerase activity by disrupting the catalytic site.
| Metabolism | Emtricitabine: undergoes limited metabolism via oxidation and glucuronidation, with the majority excreted unchanged in urine. Rilpivirine: primarily metabolized by CYP3A4 enzyme system. |
| Excretion | Renal: 88% as unchanged emtricitabine, 8% as metabolites; Fecal: 10%; Biliary: negligible. |
| Half-life | Emtricitabine: 10 h; Tenofovir alafenamide: 0.51 h (active metabolite tenofovir diphosphate intracellular half-life >60 h). |
| Protein binding | Emtricitabine: <4%; Tenofovir: ~80% (to plasma proteins, specific proteins not extensively characterized). |
| Volume of Distribution | Emtricitabine: 1.4 L/kg; Tenofovir: 0.5–0.8 L/kg; Tenofovir alafenamide: 0.5 L/kg. Indicates extensive tissue distribution including lymphocytes. |
| Bioavailability | Oral: Emtricitabine 93%; Tenofovir alafenamide (as prodrug) not reported separately; in fixed-dose combination, bioavailability is comparable to single agents. |
| Onset of Action | Oral: Peak plasma concentrations at 1.5–2 h; intracellular tenofovir diphosphate levels reach steady state within 7 days. |
| Duration of Action | Oral: Dosing every 24 h due to intracellular half-life of active metabolites; maintains virologic suppression with once-daily administration. |
One tablet orally once daily, each containing emtricitabine 200 mg, tenofovir alafenamide 25 mg, and rilpivirine 25 mg.
| Dosage form | TABLET |
| Renal impairment | Not recommended in patients with creatinine clearance (CrCl) <30 mL/min. No dose adjustment required for CrCl ≥30 mL/min. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment. Not recommended in severe hepatic impairment. |
| Pediatric use | Approved for adolescents aged ≥12 years and weighing ≥35 kg: one tablet orally once daily. Not recommended for patients <12 years or <35 kg. |
| Geriatric use | No specific dose adjustment required; use with caution due to age-related renal and hepatic decline, and monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ODEFSEY (ODEFSEY).
| Breastfeeding | ODEFSEY is not recommended during breastfeeding because emtricitabine and tenofovir are excreted in human milk, potentially leading to HIV transmission and adverse effects in the infant. The milk-to-plasma (M/P) ratio is not established for this formulation; for tenofovir disoproxil fumarate, the M/P ratio is approximately 0.01-0.03. There are insufficient data to assess safety; therefore, breastfeeding should be avoided. |
| Teratogenic Risk | ODEFSEY contains tenofovir alafenamide and emtricitabine, both classified as FDA Pregnancy Category B. Based on human pregnancy data, there is no increased risk of major birth defects or miscarriage. However, there are no adequate and well-controlled studies in pregnant women; animal studies showed no evidence of fetal harm. The Antiretroviral Pregnancy Registry has not identified a teratogenic signal. For trimesters 1-3, the risk remains low, but caution is advised due to limited data. Currently, no specific trimester-associated risks are identified. |
■ FDA Black Box Warning
Post-treatment acute exacerbation of hepatitis B: Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and discontinue emtricitabine, including products containing emtricitabine. Hepatic function should be monitored closely in patients coinfected with HBV who discontinue ODEFSEY. If appropriate, initiation of anti-HBV therapy may be warranted.
| Serious Effects |
["Co-administration with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)","Co-administration with drugs that significantly decrease gastric pH (e.g., proton pump inhibitors, antacids within 2 hours of dosing)","History of hypersensitivity to any component of the formulation"]
| Precautions | ["Fat redistribution","Immune reconstitution syndrome","Decreased bone mineral density with emtricitabine/rilpivirine","Drug interactions: coadministration with drugs that induce or inhibit CYP3A4 may affect rilpivirine concentrations; avoid strong inducers such as rifampin, carbamazepine, phenytoin","Depressive disorders: reported with rilpivirine-containing regimens"] |
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| Fetal Monitoring | Monitor HIV viral load and CD4+ count every 1-3 months during pregnancy. Assess renal function (serum creatinine, eGFR) regularly due to tenofovir alafenamide's renal effects. Perform liver function tests, especially in women with HBV coinfection. For the fetus, consider serial ultrasounds for growth and anatomy, though no specific monitoring is required beyond standard prenatal care. |
| Fertility Effects | No significant effects on fertility have been reported in human studies. In animal studies, tenofovir alafenamide and emtricitabine did not impair fertility in rats at clinically relevant exposures. There is no evidence of adverse impact on oogenesis or spermatogenesis. |