ODEFSEY® (emtricitabine, rilpivirine, and tenofovir alafenamide) tablets for oral use
|Mechanism of Action||ODEFSEY is a fixed dose combination of antiretroviral drugs emtricitabine (FTC), rilpivirine (RPV), and tenofovir alafenamide (TAF).|
|Pharmacodynamics (PD)||Higher than recommended doses of RPV, 75 mg once daily and 300 mg once daily (3 times and 12 times recommended daily dose in ODEFSEY) prolonged the QTc interval. TAF at the recommended dose and at a dose approximately 5 times the recommended dose did not affect the QT/QTc interval and did not prolong the PR interval. The effect of FTC on the QT interval is not known|
|Pharmacokinetics (PK)||Tmax: 4 h (RPV). 3 h (FTC) and 1 h (TAF)
Cmax (multiple dose, mcg/mL): 2.1 (FTC), NA (RPV) and 0.16 (TAF)
AUCtau (mcg.h/mL): 11.7 (FTC), 2.2 (RPV) and 0.21 (TAF)
Ctrough (mcg/mL): 0.10 (FTC), 0.08 (RPV) and NA (TAF)
Food Effect (high fat meal): 72% increased of AUC ( RPV). No change (FTC) and 53% increased of AUC (TAF).
Protein Binding (% bound): about 9 (RPV), <4 (FTC) and 80 (TAF)
Metabolism: by CYP3A (RPV), not significantly metabolized (FTC) and by Cathepsin A, hepatocytes, and minimal CYP3A (TAF).
Elimination: by metabolism (RPV), by glomerular filtration and active tubular secretion (FTC) and by metabolism (TAF)
|Exposure-Response Relationship||Pediatric subjects 12 to less than 18 years of age, antiretroviral HIV-1-infected, had comparable PK of RPV to those in HIV-1 infected adults. There was no impact of body weight on RPV PK in pediatric subjects.|
|Renal Impairment: No clinically relevant changes in mild impirment (RPV), exposure was higher in moderate impairment and no clinically relevant changes (TAF).
No dosage adjustment is recommended based on race or gender for FTC, RVP or TAF.
Hepatitis B and/or C virus coinfection had no clinically relevant effect on the exposure of RPV.
|Special Populations||Hepatic Impairment: Not studied (FTC), exposure was 47% higher in mild hepatic impairment and 5% higher in moderate hepatic impairment (RPV) and no clinically relevant changes (TAF).
Age did not have a clinically relevant effect on exposures of TAF up to 75 years of age. RVP and FTC have not been fully evaluated in the elderly..
|Drug Interactions||RPV is primarily metabolized by CYP3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of RPV.
Drugs that strongly affect Pgp activity (e.g., cyclosporine) may lead to changes in TAF absorption. Drugs that induce P-gp activity are expected to decrease the absorption of TAF which may lead to loss of therapeutic effect of ODEFSEY and development of resistance. Co-administration of ODEFSEY with other drugs that inhibit Pgp may result in increased absorption and plasma concentrations of TAF and possible adverse events.
Co-administration of RPV with drugs that increase gastric pH may decrease plasma concentrations of RPV and lead to loss of virologic response and possible resistance to RPV.