Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide)

Odefsey is a prescription medicine that is used to treat Human Immunodeficiency Virus-1 (HIV-1) in adults and children who weigh at least 77 pounds (35 kg):

• who have not received anti-HIV-1 medicines in the past and who have an amount of HIV-1 in their blood (this is called "viral load") that is no more than 100,000 copies/mL, or
• to replace their current anti-HIV-1 medicines for people whose healthcare provider determines that they meet certain requirements.

HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). Odefsey does not cure HIV-1 or AIDS.

Odefsey contains the prescription medicines emtricitabine, rilpivirine and tenofovir alafenamide.

It is not known if Odefsey is safe and effective in children under 12 years of age or who weigh less than 77 lb (35 kg).

Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) is a fixed-dose combination tablet containing emtricitabine (FTC), rilpivirine (RPV), and tenofovir alafenamide (TAF) for oral administration.

• FTC, a synthetic nucleoside analog of cytidine, is an HIV-1 nucleoside analog reverse transcriptase inhibitor (HIV-1 NRTI).
• RPV is an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI).
• TAF, an HIV-1 NRTI, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.

Odefsey can cause serious side effects, including:

Worsening of Hepatitis B virus infection. If you have hepatitis B virus (HBV) infection and take Odefsey, your HBV may get worse (flare-up) if you stop taking Odefsey. A "flare-up" is when your HBV infection suddenly returns in a worse way than before.

• Do not run out of Odefsey. Refill your prescription or talk to your healthcare provider before your Odefsey is all gone.
• Do not stop taking Odefsey without first talking to your healthcare provider.
• If you stop taking Odefsey, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your HBV infection. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking Odefsey.

Testing Prior To Initiation And During Treatment With Odefsey

• Prior to or when initiating Odefsey, test patients for hepatitis B virus infection.
• Prior to or when initiating Odefsey, and during treatment with Odefsey, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.

Recommended Dosage

• Odefsey is a three-drug fixed dose combination product containing 200 mg of emtricitabine (FTC), 25 mg of rilpivirine (RPV), and 25 mg of tenofovir alafenamide (TAF).
• The recommended dosage of Odefsey is one tablet taken orally once daily with a meal in adults and pediatric patients with body weight at least 35 kg and creatinine clearance greater than or equal to 30 mL per minute.

Recommended Dosage During Pregnancy

• For pregnant patients who are already on Odefsey prior to pregnancy and are virologically suppressed (HIV-1 RNA less than 50 copies per mL), one tablet of Odefsey taken once daily may be continued.
• Lower exposures of rilpivirine, a component of Odefsey, were observed during pregnancy, therefore viral load should be monitored closely.

Not Recommended In Patients With Severe Renal Impairment

• Odefsey is not recommended in patients with:
  • severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute); or
  • end stage renal disease (ESRD; estimated creatinine clearance below 15 mL per minute) who are not receiving chronic hemodialysis.

Not Recommended With Other Antiretroviral Medications

• Because Odefsey is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

Drugs Inducing Or Inhibiting CYP3A Enzymes

• RPV is primarily metabolized by CYP3A, and drugs that induce or inhibit CYP3A may affect the clearance of RPV.
• Coadministration of RPV and drugs that induce CYP3A may result in decreased plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs.
• Coadministration of RPV and drugs that inhibit CYP3A may result in increased plasma concentrations of RPV and possible adverse events.

Drugs Inducing Or Inhibiting P-Glycoprotein

• TAF, a component of Odefsey, is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3.
• Drugs that strongly affect P-gp and BCRP activity may lead to changes in TAF absorption (see Table 3).
• Drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentration of TAF, which may lead to loss of therapeutic effect of Odefsey and development of resistance.
• Coadministration of Odefsey with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF.

Drugs Increasing Gastric pH

• Coadministration 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 or to the class of NNRTIs.
• Use of RPV with proton pump inhibitors is contraindicated and use of RPV with H₂-receptor antagonists requires staggered administration.

QT Prolonging Drugs

There is limited information available on the potential for a pharmacodynamic interaction between RPV and drugs that prolong the QTc interval. In a study of healthy subjects, 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. Consider alternative medications to Odefsey in patients taking a drug with a known risk of Torsade de Pointes.

Drugs Affecting Renal Function

• Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of Odefsey with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions.
• Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to,
  • acyclovir,
  • cidofovir,
  • ganciclovir,
  • valacyclovir,
  • valganciclovir,
  • aminoglycosides (e.g., gentamicin), and
  • high-dose or multiple NSAIDs.

Significant Drug Interactions

• Table 3 provides a listing of established or potentially clinically significant drug interactions with recommended steps to prevent or manage the drug interaction (the table is not all inclusive).
• The drug interactions described are based on studies conducted with either Odefsey, the components of Odefsey (FTC, RPV and TAF) as individual agents, or are predicted drug interactions that may occur with Odefsey. 

Table 3 Significant* Drug Interactions

Drugs Without Clinically Significant Interactions With Odefsey

• Based on drug interaction studies conducted with the fixed dose combination or components of Odefsey, no clinically significant drug interactions have been observed when Odefsey is combined with the following drugs:
  • acetaminophen,
  • atorvastatin,
  • chlorzoxazone,
  • digoxin,
  • ethinyl estradiol,
  • ledipasvir,
  • metformin,
  • midazolam,
  • norethindrone,
  • norgestimate,
  • sildenafil,
  • simeprevir,
  • sofosbuvir,
  • velpatasvir, and
  • voxilaprevir.

• Available data from the APR show no increase in the risk of overall major birth defects with first trimester exposure for emtricitabine (FTC) or rilpivirine (RPV) compared with the background rate for major birth defects of 2.7% in a US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
• There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to Odefsey during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
• The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants, to avoid risking postnatal transmission of HIV.