Emtricitabine-Rilpivirine-Tenofovir AF

Emtricitabine-Rilpivirine-Tenofovir AF is a combination medication indicated as a complete regimen for treatment of HIV-1 infection in treatment-naïve adults with HIV-1 RNA ≤100,000 copies/mL, and in certain virologically suppressed (HIV-1 RNA <50 copies/mL) patients on a stable antiretroviral therapy (ART) regimen at start of therapy in order to replace their current ART regimen 

• Emtricitabine-Rilpivirine-Tenofovir AF is available under the following different brand names: Odefsey

Common side effects of Emtricitabine-Rilpivirine-Tenofovir AF include:

• depressive disorders (depressed mood, depression, general unease, mood changes, negative thoughts, suicide attempts, suicidal ideation)
• insomnia
• headache
• nausea
• drowsiness
• dizziness
• abdominal pain
• rash
• weight gain
• redistribution of body fat

Serious side effects of Emtricitabine-Rilpivirine-Tenofovir AF include:

• severe acute exacerbations of hepatitis B
• hepatotoxicity
• depressive disorders (depressed mood, depression, general unease, mood changes, negative thoughts, suicide attempts, suicidal ideation)

Rare side effects of Emtricitabine-Rilpivirine-Tenofovir AF include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 200 mg/25 mg/25 mg

HIV Infection

Adult dosage

• 1 tablet (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir 25 mg) orally every day with food

Pediatric dosage

• Children younger than 12 years or weighing less than 35 kg: Safety and efficacy not established
• Children 12 years and older and weighing 35 kg and more: 1 tablet (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir 25 mg) orally every day with food

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Emtricitabine-Rilpivirine-Tenofovir AF has severe interactions with the following drugs:
  • carbamazepine
  • dexamethasone
  • dexlansoprazole
  • efavirenz
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • eslicarbazepine acetate
  • fezolinetant
  • lamivudine
• Emtricitabine-Rilpivirine-Tenofovir AF has serious interactions with at least 37 other drugs
• Emtricitabine-Rilpivirine-Tenofovir AF has moderate interactions with at least 198 other drugs
• Emtricitabine-Rilpivirine-Tenofovir AF has minor interactions with the following drugs:
  • chloroquine
  • crizotinib
  • nirmatrelvir/ritonavir

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Coadministration of the following drugs
• Anticonvulsants (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin)
• Antimycobacterials (eg, rifabutin, rifampin, rifapentine)
• Glucocorticoid systemic dexamethasone (more than a single dose)
• St. John’s wort
• Proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Emtricitabine-Rilpivirine-Tenofovir AF?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Emtricitabine-Rilpivirine-Tenofovir AF?”

Cautions

• Severe acute exacerbation of hepatitis B in patients coinfection with HIV-1 and HBV
• Severe skin and hypersensitivity reactions reported, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS) with rilpivirine (RPV)-containing regimens; discontinue therapy immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia; monitor and initiate appropriate therapy
• Depressive disorders (including depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) reported with rilpivirine; promptly evaluate patients with severe depressive symptoms to assess whether symptoms are related to therapy, and determine whether risks of continued therapy outweigh benefits
• Fat redistribution and accumulation observed with ART therapy
• 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
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases reported; suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations)
• Immune reconstitution syndrome
• Immune reconstitution syndrome is reported in patients treated with combination antiretroviral therapy; during the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop inflammatory responses to indolent or residual opportunistic infections, including Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis, which may necessitate further evaluation and treatment
• Autoimmune disorders, including Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis, have been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable and can occur many months after initiation of treatment
• Hepatotoxicity
  • Hepatic adverse events reported in patients receiving an RPV-containing regimen; patients with underlying hepatitis B or C virus infection, or marked elevations in liver-associated tests prior to treatment, may be at increased risk for worsening or development of liver-associated test elevations
  • A few cases of hepatic toxicity were reported in adult patients receiving an RPV-containing regimen who had no preexisting hepatic disease or other identifiable risk factors
  • Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy is recommended in patients with underlying hepatic disease, such as hepatitis B or C, or in patients with marked elevations in liver-associated tests prior to treatment initiation
  • Liver-associated test monitoring should be considered for patients without preexisting hepatic dysfunction or other risk factors
• New onset or worsening renal impairment
  • Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome reported with TAF-containing products; while most of these cases were characterized by potential confounders that may have contributed to reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse
  • Therapy is not recommended in patients with estimated creatinine clearance of 15 to less than 30 mL/min, or patients with estimated creatinine clearance of less than 15 mL/min who are not receiving chronic hemodialysis
  • Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents, including nonsteroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions
  • Prior to or when initiating therapy, and during treatment 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; discontinue therapy in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome
  • Drug interactions overview
  • Coadministration with P-gp/BCRP inhibitors may increase absorption and plasma concentration of tenofovir AF; P-gp inducer may decrease 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 with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs
• Rilpivirine
  • Rilpivirine is a CYP3A4 substrate
  • Coadministration with CYP3A inducers may decrease plasma levels of RPV loss of virologic response and possible resistance to RPV or to the class of NNRTIs
  • Coadministration with CYP3A inhibitor may increase plasma levels of RPV
  • Supratherapeutic rilpivirine doses (ie, 75 mg and 300 mg every day) shown to prolong the QTc interval; caution when coadministered with a drug known to increase the risk of torsade de pointes
  • Rilpivirine use with proton pump inhibitors is contraindicated and use of RPV with H2-receptor antagonists requires staggered administration 

Pregnancy and Lactation

• Pregnancy exposure registry monitors pregnancy outcomes in individuals exposed to treatment during pregnancy
• Register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
• Available data from the APR show no statistically significant difference in the overall risk of major birth defects for emtricitabine (FTC), rilpivirine (RPV) or tenofovir alafenamide (TAF) 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); the rate of miscarriage is not reported in the APR
• TAF use in women during pregnancy has not been evaluated; emtricitabine (FTC) and rilpivirine (RPV) use during pregnancy has been evaluated in a limited number of women reported to the APR
• Available data 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%
• Based on HIV-1-infected pregnant individuals who completed a clinical trial through a postpartum period with an RPV-based regimen, no dose adjustments are required for pregnant patients who are already on a stable RPV-containing regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA of less than 50 copies per mL)
• Closely monitor viral load; lower exposures of RPV were observed during pregnancy
• Lactation
  • The CDC recommend that HIV-infected mothers not breastfeed their infants, to avoid risking postnatal transmission of HIV
  • Based on published data, FTC has shown to be present in human breast milk;
  • Unknown if RPV and TAF are present in human breast milk; RPV is present in rat milk and tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration
  • Because of the potential for: HIV transmission (in HIV-negative infants); developing viral resistance (in HIV-positive infants); and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed