Dosing and uses of Odefsey (emtricitabine/rilpivirine/tenofovir AF)
Adult dosage forms and strengths
emtricitabine/rilpivirine/tenofovir AF
tablet
- 200mg/25mg/25mg
HIV Infection
Indicated as a complete regimen for the treatment of HIV-1 infection as initial therapy in antiretroviral-naïve patients who are aged ≥12 yr with HIV-1 RNA ≤100,000 copies/mL
May also be used to replace a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual drug components
Dosage
- 1 tablet PO qDay with food
- Prior to initiation, test patients for hepatitis B infection
Dosage modifications
Renal impairment
- Mild-to-moderate (eCrCl ≥30 mL/min): No dosage adjustment required
- Severe or ESRD (eCrCl <30 mL/min): Not recommended; data are insufficient in this population
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment required
- Severe (Child-Pugh C): Not recommended; data are insufficient in this population
Dosing Considerations
Tenofovir alafenamide (TAF) is a prodrug of tenofovir that has high antiviral efficacy similar to and at a dose less than one-tenth that of the original formulation of tenofovir prodrug (ie, tenofovir disoproxil fumarate [TDF])
TAF provides lower levels of drug in the bloodstream, but higher intracellular levels compared with TDF
TAF appears to be associated with less kidney toxicity and less decrease in bone density than previously approved tenofovir-containing regimens; although not recommended for patients with severe renal impairment, those with moderate renal impairment can take TAF
Pediatric dosage forms and strengths
emtricitabine/rilpivirine/tenofovir AF
tablet
- 200mg/25mg/25mg
HIV Infection
Indicated as a complete regimen for the treatment of HIV-1 infection as initial therapy in antiretroviral-naïve patients who are aged ≥12 yr with HIV-1 RNA ≤100,000 copies/mL
May also be used to replace a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual drug components
Dosage
- <12 years: Safety and efficacy not established
- ≥12 years and weight ≥35 kg: 1 tablet PO qDay with food
- Prior to initiation, test patients for hepatitis B infection
Dosage modifications
Renal impairment
- Mild-to-moderate (eCrCl ≥30 mL/min): No dosage adjustment required
- Severe or ESRD (eCrCl <30 mL/min): Not recommended; data are insufficient in this population
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment required
- Severe (Child-Pugh C): Not recommended; data are insufficient in this population
Dosing Considerations
Tenofovir alafenamide (TAF) is a prodrug of tenofovir that has high antiviral efficacy similar to and at a dose less than one-tenth that of the original formulation of tenofovir prodrug (ie, tenofovir disoproxil fumarate [TDF])
TAF provides lower levels of drug in the bloodstream, but higher intracellular levels compared with TDF
TAF appears to be associated with less kidney toxicity and less decrease in bone density than previously approved tenofovir-containing regimens; although not recommended for patients with severe renal impairment, those with moderate renal impairment can take TAF
Odefsey (emtricitabine/rilpivirine/tenofovir AF) adverse (side) effects
1-10%
Nausea (10%)
Mild/moderate depression (rilpivirine) (9%)
Severe depression (rilpivirine) (1%)
Frequency not defined
Lactic acidosis
Exacerbation of hepatitis B in coinfected patients
Postmarketing Reports
Rilpivirine
- Metabolism and nutrition disorders: Weight increased
- Skin and subcutaneous tissue disorders: Severe skin and hypersensitivity reactions including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)
- Renal and urinary disorders: Nephrotic syndrome
Warnings
Black box warnings
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs (tenofovir), a component of Odefsey, in combination with other antiretrovirals
Not approved for chronic hepatitis B virus (HBV) infection and the safety and efficacy have not been established in patients coinfected with HBV and HIV-1; severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 (including thos who have discontinued emtricitabine or tenofovir)
Hepatic function should be monitored closely in these patients; if appropriate, initiation of antihepatitis B therapy may be warranted
Contraindications
Coadministration with drugs that significantly decrease rilpivirine plasma concentrations due to CYP3A enzyme induction (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, dexamethasone [>1 dose], St John’s wort)
Coadministration with drugs that increase gastric pH (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), which may decrease rilpivirine absorption and result in decreased rilpivirine plasma concentrations
Cautions
Lactic acidosis and severe hepatomegaly with steatosis reported (see Black box warnings)
Patients with HIV-1 infection should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy (ART); not approved for the treatment of chronic HBV infection (see Black box warnings)
Severe skin and hypersensitivity reactions reported, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), with rilpivirine-containing regimens; immediately discontinue treatment if hypersensitivity or rash with systemic symptoms or elevations in hepatic serum biochemistries develop and closely monitor clinical status, including hepatic serum biochemistries
Concomitant use with other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effects and possible development of resistance
Supratherapeutic rilpivirine doses (ie, 75 mg and 300 mg qDay) have been shown to prolong the QTc interval; caution when coadministered with a drug known to increase risk of torsade de pointes
Rilpivirine may increase risk for depressive disorders
Hepatic adverse effects reported with rilpivirine; patients with underlying hepatitis B or C, or marked increased transaminases prior to treatment, may be at increased risk; monitor for hepatotoxicity before initiating and during treatment (see Dosage modifications)
Fat redistribution and accumulation observed with ART therapy
Immune reconstitution syndrome reported, including the occurrence of autoimmune disorders (eg, Grave disease, polymyositis, Guillain-Barre syndrome) with variable time to onset
Decreases in bone mineral density (BMD) and cases of osteomalacia associated with proximal renal tubulopathy reported with tenofovir; consider monitoring BMD with a history of pathologic fracture or if risk factors for bone loss exist
New-onset or worsening renal impairment
- Estimated CrCl, urine glucose, and urine protein should be assessed in all patients before initiating
- Avoid concurrent or recent use of nephrotoxic drugs
- Cases of acute renal failure and Fanconi syndrome reported with the use of tenofovir prodrugs; monitor estimated CrCl, urine glucose, and urine protein in all patients prior to initiating and during therapy; additionally, monitor serum phosphorus in patients with or at risk for renal impairment
- Discontinue drug if clinically significant decreases in renal function or evidence of Fanconi syndrome develop
- Do not initiate with CrCl <30 mL/min
Pregnancy
Pregnancy
There are insufficient human data on the use of Odefsey during pregnancy to inform a drug-associated risk of birth defects and miscarriage
Tenofovir alafenamide (TAF) and rilpivirine (RPV) use in women during pregnancy has not been evaluated; however, emtricitabine (FTC) use during pregnancy has been evaluated in a limited number of women reported to the Antiretroviral Pregnancy Registry (APR)
Available data from the APR show no difference in the risk of overall major birth defects for FTC (2.4%) compared with the background rate for major birth defects of 2.7%
An ART pregnancy registry has been established; healthcare providers should encourage patients to register (1-800-258-426)
Lactation
The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants, to avoid risking postnatal transmission of HIV
FTC has been shown to be present in human breast milk; it is unknown if RPV and TAF are present in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Odefsey (emtricitabine/rilpivirine/tenofovir AF)
Mechanism of action
Emtricitabine: Nucleoside reverse transcriptase inhibitor (NRTI); following phosphorylation, interferes with HIV viral DNA polymerase and inhibits viral replication; cytosine analogue
Rilpivirine: Antiviral agent; diarylpyrimidine non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1; inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase
Tenofovir AF: Nucleotide reverse transcriptase inhibitor (NRTI); prodrug of tenofovir; compared with tenofovir disoproxil fumarate (tenofovir DF, Viread), tenofovir alafenamide (AF) is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile; inhibits HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination
Administration
Oral Administration
Take once a day with a meaL
Instruct patients not to miss a dose, as it can result in development of antimicrobial resistance
Storage
Store below 30°C (86°F)
Keep container tightly closed
Dispense only in original container
