Version May 2024
Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and hepatitis B virus (HBV) and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate, and may occur with discontinuation of emtricitabine/rilpivirine/tenofovir alafenamide.
Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue emtricitabine/rilpivirine/tenofovir alafenamide. If appropriate, anti-hepatitis B therapy may be warranted.
HIV-1 infection, treatment: Oral: One tablet (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg) once daily. Note: Do not use in patients with HIV RNA ≥100,000 copies/mL and/or CD4 count ≤200 cells/mm3 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use is not recommended.
End-stage renal disease on hemodialysis: No dosage adjustment necessary; administer after hemodialysis on dialysis days.
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustments necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Rilpivirine, emtricitabine, and tenofovir alafenamide: Pediatric drug information")
Note: Product is a fixed-dose combination; use not recommended in other weight groups.
HIV-1 infection, treatment: Note: Do not use in patients with HIV RNA ≥100,000 copies/mL (Ref). Gene mutation and antiretroviral resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.
Children and Adolescents weighing ≥35 kg: Oral: Odefsey (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg per tablet): One tablet once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents weighing ≥35 kg:
Baseline impairment:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute at initiation of therapy: Use is not recommended.
End-stage renal disease on hemodialysis: Adolescents: No dosage adjustment necessary; administer after hemodialysis on dialysis days (Ref).
Nephrotoxicity during therapy (patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome): Discontinue therapy.
Children and Adolescents weighing ≥35 kg:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage recommendations in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
1% to 10%:
Gastrointestinal: Diarrhea (1%), flatulence (≤1%), nausea (1%)
Nervous system: Abnormal dreams (1%), headache (2%), sleep disturbance (2%)
Neuromuscular & skeletal: Decreased bone mineral density (1% to 2%)
Frequency not defined: Endocrine & metabolic: Changes in serum lipids
Concurrent use with certain drugs whose coadministration may result in loss of virologic response and possible resistance to emtricitabine/rilpivirine/tenofovir alafenamide or to the class of non-nucleoside reverse transcriptase inhibitors (eg, carbamazepine, systemic dexamethasone [>1 dose], oxcarbazepine, phenobarbital, phenytoin, proton pump inhibitors [dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole], rifampin, rifapentine, St John's wort).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to emtricitabine, rilpivirine, tenofovir alafenamide, or any component of the formulation.
Concerns related to adverse effects:
• Depressive disorders: Rilpivirine may cause depression, depressed mood, dysphoria, major depression, mood changes, negative thoughts, suicide attempts, or suicidal ideation. Promptly evaluate patients with severe depressive symptoms and reevaluate risk versus benefit of continued combination therapy.
• Hepatotoxicity: Hepatotoxicity has been reported with rilpivirine-containing regimens. Patients with hepatitis B or C or increased baseline liver function tests may be at greater risk, although some cases have occurred in patients with no preexisting disease or hepatic disease risk factors. Evaluate liver function tests in patients with increased baseline liver function tests or with hepatitis B or C prior to treatment initiation and periodically during therapy; also consider evaluation of patients with no preexisting hepatic disease or hepatic disease risk factors.
• Hypersensitivity: Hypersensitivity and severe skin reactions have been reported, including drug reaction with eosinophilia and systemic symptoms (DRESS), with regimens containing rilpivirine. Some skin reactions were accompanied by constitutional symptoms (eg, fever); other skin reactions were associated with organ dysfunction (eg, hepatic serum biochemistry elevations). In clinical trials, treatment-related rashes ≥ grade 2 were reported in 1% of patients. Most rashes were grade 1 or 2 and occurred within the first 4 to 6 weeks of therapy. Monitor laboratory parameters and clinical status; discontinue if any severe hypersensitivity or skin rash (including, but not limited to, severe rash or rash accompanied by angioedema, blisters, conjunctivitis, eosinophilia, facial edema, fever, hepatitis, or mucosal involvement) develops.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).
• QT prolongation: In healthy subjects, supratherapeutic dosages of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram; consider alternative therapy in patients at high risk for torsades de pointes or when coadministered with medications with known risk for torsades de pointes.
• Renal toxicity: Renal toxicity (acute renal failure, Fanconi syndrome, and/or proximal renal tubulopathy) has been reported with use of tenofovir alafenamide-containing products; most cases were characterized by potential confounders that may have contributed to the renal events; however, it is also possible these factors may have predisposed patients to tenofovir-related adverse events. Patients with impaired renal function and those with concurrent or recent nephrotoxic therapy (including NSAID use) are at an increased risk. Discontinue use in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
Disease-related concerns:
• Renal impairment: Use is not recommended in patients with CrCl <30 mL/minute (unless receiving hemodialysis).
Emtricitabine-associated hyperpigmentation occurs more frequently in pediatric patients (32%) than in adults.
Incidence of some adverse reactions may be higher in pediatric patients 12 to 18 years of age receiving rilpivirine as compared to adults. In a small, phase 2 pediatric clinical trial (n=36), adverse reactions following receipt of rilpivirine in combination with other antiretrovirals were similar to those in adults, with a higher incidence of some reactions (eg, headache, dizziness, depression); most were grade 1 or 2. For depressive disorders, the incidence of grade 3 and 4 depressive disorders (regardless of causality) was 5.6% (vs 1% in adults), including 1 suicide attempt. None of these pediatric patients discontinued therapy due to their depressive symptoms.
Through disruption in vitamin D metabolism, decreases in bone mineral density (BMD) have been observed with tenofovir alafenamide (TAF) after 48 weeks of treatment; however, the incidence and negative impact on BMD is less than that observed with tenofovir disoproxil fumarate (TDF). Additionally, TAF is associated with less renal toxicity than TDF but equal antiviral efficacy. A higher incidence of dyslipidemia has been reported with TAF than TDF. TAF is preferred over TDF whenever possible; do not use TAF and TDF concomitantly (HHS [pediatric] 2021).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Odefsey: Emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir alafenamide 25 mg
No
Tablets (Odefsey Oral)
200-25-25 mg (per each): $144.93
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Odefsey: Emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir alafenamide 25 mg
Oral: Administer with a meal (>390 kcal) (Ref).
Oral: Administer with a moderate to high-fat meal (children: ≥500 kcal; adolescents: ≥390 kcal); a protein drink alone is not sufficient (Ref).
HIV-1 infection, treatment: Treatment of HIV-1 infection (as a complete regimen) in adult and pediatric patients weighing ≥35 kg as initial therapy in those with no antiretroviral treatment history with HIV-1 RNA ≤100,000 copies/mL; or to replace a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components.
Limitations of use: More rilpivirine-treated patients with no history of antiretroviral treatment with HIV-1 RNA >100,000 copies/mL at therapy initiation experienced virologic failure (HIV-1 RNA ≥50 copies/mL) compared to rilpivirine-treated patients with HIV-1 RNA ≤100,000 copies/mL.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapy
Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Risk X: Avoid combination
Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Antacids: May decrease the serum concentration of Rilpivirine. Management: Administer antacids at least 2 hours before or 4 hours after oral rilpivirine when used with most rilpivirine products. However, administer antacids at least 6 hours before or 4 hours after the rilpivirine/dolutegravir combination product. Risk D: Consider therapy modification
Antihepaciviral Combination Products: May increase the serum concentration of Rilpivirine. Risk X: Avoid combination
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
CarBAMazepine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cobicistat: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Rilpivirine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Rilpivirine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced rilpivirine efficacy (eg, loss of virologic response or resistance). Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Rilpivirine. Risk C: Monitor therapy
DexAMETHasone (Systemic): May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Didanosine: Rilpivirine may decrease the absorption of Didanosine. Didanosine may decrease the absorption of Rilpivirine. More specifically, simultaneous coadministration of these drugs creates a conflict between recommendations to administer with (rilpivirine) and without (didanosine) food. Management: Administer didanosine on an empty stomach at least 2 hours before or 4 hours after rilpivirine, due to the requirement that rilpivirine be administered with food. Risk D: Consider therapy modification
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Risk X: Avoid combination
Fosphenytoin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Histamine H2 Receptor Antagonists: May decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists (H2RAs) at least 12 hours before or 4 hours after oral rilpivirine. Risk D: Consider therapy modification
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Ketoconazole (Systemic): May increase the serum concentration of Rilpivirine. Rilpivirine may decrease the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Levomethadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Levomethadone. Management: Levomethadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Macrolide Antibiotics: May increase the serum concentration of Rilpivirine. Management: Consider the use of azithromycin or another non-macrolide alternative when appropriate to avoid this potential interaction. Risk D: Consider therapy modification
Methadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the metabolism of Methadone. Management: Methadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the nephrotoxic effect of Tenofovir Products. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
OXcarbazepine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
OXcarbazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Tenofovir Alafenamide. Management: Consider alternatives to the use of P-gp inducers with tenofovir alafenamide. If combined, monitor for reduced tenofovir alafenamide concentrations and efficacy, and for the development of resistance. Risk D: Consider therapy modification
PHENobarbital: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
PHENobarbital: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Phenytoin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Primidone: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Primidone: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Reverse Transcriptase Inhibitors (Non-Nucleoside): May enhance the adverse/toxic effect of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, efavirenz and nevirapine may decrease the serum concentrations of other non-nucleoside reverse transcriptase inhibitors. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, delavirdine may increase the serum concentration of etravirine. Risk X: Avoid combination
Rifabutin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
RifAMPin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
RifAMPin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Rifapentine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Rifapentine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Ritonavir: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
Saquinavir: Rilpivirine may enhance the arrhythmogenic effect of Saquinavir. Saquinavir may increase the serum concentration of Rilpivirine. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Tacrolimus (Systemic): Tenofovir Products may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tipranavir: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
The Health and Human Services perinatal HIV guidelines consider this fixed-dose combination an alternative regimen for patients with HIV who are not yet pregnant but are trying to conceive (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
The Health and Human Services perinatal HIV guidelines recommend this fixed-dose combination an alternative regimen for initiation in pregnant patients with HIV who are antiretroviral naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Patients who become pregnant while taking this combination may continue if viral suppression is effective and the regimen is well tolerated. More frequent monitoring is recommended during pregnancy. This fixed-dose combination may be considered for patients when significant drug interactions would occur with preferred agents or in patients who need the convenience of a co-formulated single dose tablet in a once-daily regimen but are not eligible for preferred agents. This combination should only be used in pregnant patients with a pretreatment HIV RNA ≤100,000 copies/mL or CD4 cell count ≥200 cells/mm3 (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
Emtricitabine and tenofovir are present in breast milk; it is not known if rilpivirine is present in breast milk.
Refer to individual monographs for additional information.
Take with a meal.
CD4 count, HIV RNA plasma levels; serum creatinine, estimated creatinine clearance, urine glucose, urine protein (prior to initiation and as clinically indicated during therapy); serum phosphorus (patients with chronic kidney disease); hepatic function tests, bone density (patients with a history of bone fracture or have risk factors for bone loss); fever, skin reactions, and/or hypersensitivity reactions; HBV testing (prior to or when initiating therapy). Patients with HIV and HBV coinfection should be monitored for several months following therapy discontinuation.
Non-nucleoside, nucleoside, and nucleotide reverse transcriptase inhibitor combination; rilpivirine binds to reverse transcriptase and does not require intracellular phosphorylation for antiviral activity; emtricitabine is a cytidine analogue while tenofovir alafenamide fumarate (TAF) is an analog of adenosine 5'-monophosphate. Each drug interferes with HIV viral RNA dependent DNA polymerase activities resulting in inhibition of viral replication.
See individual agents.
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