Odefsey

• Generic Name: emtricitabine, rilpivirine, and tenofovir alafenamide fixed-dose combination tablets
• Brand Name: Odefsey

Odefsey (Emtricitabine, Rilpivirine, and Tenofovir Alafenamide Fixed-dose Combination Tablets) side effects drug center

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• Drug Comparison
  Triumeq vs. Odefsey

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

• Overview
• Professional Information

 

Odefsey Side Effects Center

What Is Odefsey?

Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) is a combination of two HIV nucleoside analog reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years of age and older as initial therapy in those with no antiretroviral treatment history with HIV-1 RNA less than or equal to 100,000 copies per mL; or to replace a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) for at least six months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Odefsey.

What Are Side Effects of Odefsey?

Common side effects of Odefsey include:

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

Dosage for Odefsey?

The recommended dosage of Odefsey is one tablet taken orally once daily with a meal.

What Drugs, Substances, or Supplements Interact with Odefsey?

Odefsey may interact with antacids, antimycobacterials, azole antifungals, H2-receptor antagonists, macrolide or ketolide antibiotics, and narcotics. Tell your doctor all medications and supplements you use.

Odefsey During Pregnancy and Breastfeeding

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Odefsey during pregnancy. Consult your doctor for more information on Odefsey use during pregnancy. Women infected with HIV should not breastfeed due to the potential for HIV transmission.

Additional Information

Our Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Odefsey Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: a blistering skin rash, fever, mouth sores, eye redness, swollen glands, trouble breathing or swallowing, right-sided upper stomach pain, unusual bruising, or dark urine.

Call your doctor at once if you have:

• depression or mood changes, anxiety, restlessness, suicidal thoughts or actions;
• kidney problems--little or no urination, swelling in your feet or ankles, feeling tired or short of breath;
• lactic acidosis--unusual muscle pain, trouble breathing, stomach pain, vomiting, irregular heart rate, dizziness, feeling cold, or feeling very weak or tired; or
• liver problems--stomach pain, nausea, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

This medicine affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss;
• trouble speaking or swallowing, problems with balance or eye movement, weakness or prickly feeling; or
• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.

Common side effects may include:

• headache, dizziness, tiredness;
• depressed mood, trouble sleeping, strange dreams;
• rash; or
• nausea, diarrhea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Odefsey (Emtricitabine, Rilpivirine, and Tenofovir Alafenamide Fixed-dose Combination Tablets)

 

Odefsey Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in other sections of the labeling:

• Severe Acute Exacerbations of Hepatitis B [see WARNINGS AND PRECAUTIONS]
• Skin and Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Depressive Disorders [see WARNINGS AND PRECAUTIONS]
• New Onset or Worsening Renal Impairment [see WARNINGS AND PRECAUTIONS]
• Lactic Acidosis/Severe Hepatomegaly with Steatosis [see WARNINGS AND PRECAUTIONS]
• Immune Reconstitution Syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug (or a drug given in various combinations with other concomitant therapy) cannot be directly compared to rates in the clinical trials of another drug (or drug given in the same or different combination therapy) and may not reflect the rates observed in practice.

Adverse Reactions In Clinical Trials Of ODEFSEY In Virologically-Suppressed Adult Subjects With HIV-1 Infection

The safety of ODEFSEY in virologically-suppressed adults is based on Week 48 data from two randomized, double-blinded, active-controlled clinical trials, 1160 and 1216, that enrolled 1505 adult subjects who were virologically-suppressed for at least 6 months. Both trials were designed to compare switching to ODEFSEY to maintaining efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) or emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) in Trials 1160 and 1216, respectively. A total of 754 subjects received one tablet of ODEFSEY daily [see Clinical Studies].

The most common adverse reactions (all Grades) reported in at least 2% of subjects in the ODEFSEY group across Trials 1216 and 1160 were headache and sleep disturbances (Table 1). Over 98% of the adverse reactions in the ODEFSEY group were of mild to moderate intensity. The proportion of subjects who discontinued treatment with ODEFSEY due to adverse events, regardless of severity, was 2% compared to 1% for FTC/RPV/TDF and 2% for EFV/FTC/TDF.

Table 1 : Adverse Reactions^a (All Grades) Reported in ≥1% of HIV-1 Infected Virologically-Suppressed Adults in Trial 1160 or Trial 1216 (Week 48 analysis)

Adverse Reaction	Trial 1160		Trial 1216
	ODEFSEY (N=438)	EFV/FTC/TDF (N=437)b	ODEFSEY (N=316)	FTC/RPV/TDF (N=313)b
Headache	2%	1%	0	1%
Sleep Disturbances	2%	1%	0	<1%
Flatulence	1%	<1%	<1%	1%
Abnormal Dreams	1%	1%	0	2%
Diarrhea	1%	3%	1%	2%
Nausea	1%	1%	1%	1%
a Frequencies of adverse reactions are based on all adverse events attributed to study drugs by the investigator. b Data from Trials 1160 and 1216 do not provide an adequate basis for comparison of adverse reaction incidences between ODEFSEY and the FTC/RPV/TDF and EFV/FTC/TDF groups.

Renal Laboratory Tests

In Trial 1216, the median baseline eGFR was104 mL per minute for subjects who switched to ODEFSEY from FTC/RPV/TDF (N=316) and the mean serum creatinine decreased by 0.02 mg per dL from baseline to Week 48.

In Trial 1160, the median baseline eGFR was 110 mL per minute for subjects who switched to ODEFSEY from EFV/FTC/TDF (N=438), and the mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48.

Bone Mineral Density Effects

Changes in BMD from baseline to Week 48 were assessed by dual-energy X-ray absorptiometry (DXA) in Trials 1216 and 1160.

In Trial 1216, mean bone mineral density (BMD) increased in subjects who switched to ODEFSEY (1.61% lumbar spine, 1.04% total hip) and remained stable or decreased in subjects who remained on FTC/RPV/TDF (0.08% lumbar spine, -0.25% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 1.7% of ODEFSEY subjects and 3.0% of FTC/RPV/TDF subjects. BMD declines of 7% or greater at the femoral neck were experienced by 0% of ODEFSEY subjects and 1.2% of FTC/RPV/TDF subjects.

In Trial 1160, mean BMD increased in subjects who switched to ODEFSEY (1.65% lumbar spine, 1.28% total hip) and decreased slightly in subjects who remained on EFV/FTC/TDF (-0.05% lumbar spine, -0.13% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 2.3% of ODEFSEY subjects and 4.9% of EFV/FTC/TDF subjects. BMD declines of 7% or greater at the femoral neck were experienced by 1.4% of ODEFSEY subjects and 3.3% of EFV/FTC/TDF subjects. The long-term clinical significance of these BMD changes is not known.

Serum Lipids

Changes from baseline in total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and total cholesterol to HDL ratio for Trials 1216 and 1160 are presented in Table 2.

Table 2 : Lipid Values, Mean Change from Baseline Reported in Subjects Receiving ODEFSEY, FTC/RPV/TDF and EFV/FTC/TDF in Trials 1216 and 1160 at 48 Weeks

	Trial 1216				Trial 1160
	ODEFSEY N=316 [n=235]		FTC/RPV/TDF N=314 [n=245]		ODEFSEY N=438 [n=295]		EFV/FTC/TDF N=437 [n=308]
	Baseline mg/dL	Week 48 Changeab	Baseline mg/dL	Week 48 Changeab	Baseline mg/dL	Week 48 Changeab	Baseline mg/dL	Week 48 Changeab
Total Cholesterol (fasted)	176	+ 17	171	0	193	-7	192	-3
HDL- Cholesterol (fasted)	50	+3	48	0	56	-4	55	-2
LDL- Cholesterol (fasted)	111	+ 13	108	+ 1	118c	-1c	119	-1
Triglycerides (fasted)	116	+ 12	119	-9	139	-12	133	+3
Total Cholesterol to HDL Ratio	3.7	+0.2	3.8	+0.1	3.7	+0.2	3.8	0
a The change from baseline is the mean of within-subject changes from baseline for subjects with both baseline and Week 48 values. b Subjects who received lipid-lowering agents during the treatment period were excluded. c [n=296] for ODEFSEY group in Study 1160 for LDL-Cholesterol (fasted)

Adverse Reactions In Clinical Trials Of RPV-Containing Regimens In Treatment-Naive Adult Subjects With HIV-1 Infection

In pooled 96-week trials of antiretroviral treatment-naive HIV-1 infected adult subjects, the most common adverse reactions in subjects treated with RPV+FTC/TDF (N=550) (incidence greater than or equal to 2%, Grades 2-4) were headache, depressive disorders, and insomnia. The proportion of subjects who discontinued treatment with RPV+FTC/TDF due to adverse reactions, regardless of severity, was 2%. The most common adverse reactions that led to discontinuation in this treatment group were psychiatric disorders (1.6%) and rash (0.2%). Although the safety profile was similar in virologically-suppressed adults with HIV-1 infection who were switched to RPV and other antiretroviral drugs, the frequency of adverse events increased by 20% (N=317).

Adverse Reactions In Clinical Trials Of FTC+TAF With EVG+COBI In Treatment-Naive Adult Subjects With HIV-1 Infection

In pooled 48-week trials of antiretroviral treatment-naive HIV-1 infected adult subjects, the most common adverse reaction in subjects treated with FTC+TAF with EVG+COBI (N=866) (incidence greater than or equal to 10%, all grades) was nausea (10%). In this treatment group, 0.9% of subjects discontinued FTC+TAF with EVG+COBI due to adverse event [see Clinical Studies]. Antiretroviral treatment-naive adult subjects treated with FTC+TAF with EVG+COBI experienced mean increases of 30 mg/dL of total cholesterol, 15 mg/dL of LDL cholesterol, 7 mg/dL of HDL cholesterol and 29 mg/dL of triglycerides after 48 weeks of use.

Renal Laboratory Tests

In two 48-week trials in antiretroviral treatment-naive HIV-1 infected adults treated with FTC+TAF with elvitegravir (EVG) plus cobicistat (COBI) (N=866) with a median baseline eGFR of 115 mL per minute, mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48.

In clinical trials of FTC+TAF with EVG+COBI in treatment-naive subjects and in virologically-suppressed subjects switched to FTC+TAF with EVG+COBI with estimated creatinine clearance greater than 50 mL per minute, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI.

In a 24-week trial in adults with renal impairment (baseline eGFR 30 to 69 mL per minute) who received FTC+TAF with EVG+COBI (N=248), mean serum creatinine was 1.5 mg per dL at both baseline and Week 24. FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) subjects.

Bone Mineral Density Effects

In the pooled analysis of two 48-week trials of antiretroviral treatment-naive HIV-1 infected adult subjects, bone mineral density (BMD) from baseline to Week 48 was assessed by dual-energy X-ray absorptiometry (DXA). Mean BMD decreased from baseline to Week 48 by -1.30% with FTC+TAF with EVG+COBI at the lumbar spine and -0.66% at the total hip. BMD declines of 5% or greater at the lumbar spine were experienced by 10% of FTC+TAF with EVG+COBI subjects. BMD declines of 7% or greater at the femoral neck were experienced by 7% of FTC+TAF with EVG+COBI subjects. The long-term clinical significance of these BMD changes is not known.

Adverse Reactions In Clinical Trials In Pediatric Subjects With HIV-1 Infection

In an open-label 48-week trial of 36 antiretroviral treatment-naive HIV-1 infected pediatric subjects 12 to less than 18 years old (weighing at least 32 kg) treated with 25 mg per day of RPV and other antiretrovirals, the most common adverse reactions were headache (19%), depression (19%), somnolence (14%), nausea (11%), dizziness (8%), abdominal pain (8%), vomiting (6%) and rash (6%).

In a 24-week, open-label trial of 23 antiretroviral treatment-naive HIV-1 infected pediatric subjects aged 12 to less than 18 years old (weighing at least 35 kg) who received FTC+TAF with EVG+COBI, the safety of this combination was similar to that of adults. Among these pediatric subjects, mean BMD increased from baseline to Week 24, +1.7% at the lumbar spine and +0.8% for the total body less head. Mean changes from baseline BMD Z-scores were -0.10 for lumbar spine and -0.11 for total body less head at Week 24. Two subjects had significant (greater than 4%) lumbar spine BMD loss at Week 24.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing experience in patients receiving RPV or TAF-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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

Tenofovir alafenamide

Skin And Subcutaneous Tissue Disorders

Angioedema, urticaria, and rash

Renal And Urinary Disorders

Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome

DRUG INTERACTIONS

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 [see CLINICAL PHARMACOLOGY]. 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 [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and Table 3].

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 [see CONTRAINDICATIONS and Table 3].

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 [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. 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 [see WARNINGS AND PRECAUTIONS].

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 [see CLINICAL PHARMACOLOGY, Tables 8-11]. For list of contraindicated drugs, [see CONTRAINDICATIONS].

Table 3 : Significant^a Drug Interactions

Concomitant Drug Class: Drug Name	Effect on Concentrationb	Clinical Comment
Antacids: antacids (e.g., aluminum, magnesium hydroxide, or calcium carbonate)	↔ RPV (antacids taken at least 2 hours before or at least 4 hours after RPV) ↓  RPV (concomitant intake)	Administer antacids at least 2 hours before or at least 4 hours after ODEFSEY.
Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin	↓RPV	Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.
Antimycobacterials: rifampin rifapentine	↓ RPV	Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.
Antimycobacterials: rifabutin	↓ RPVc ↓ TAF	Coadministration of ODEFSEY with rifabutin is not recommended.
Azole Antifungal Agents: fluconazole itraconazole ketoconazole posaconazole voriconazole	↑ RPVc,d ↑ TAF ↓ ketoconazolec,d	No dosage adjustment is required when ODEFSEY is coadministered with azole antifungal agents. Clinically monitor for breakthrough fungal infections when azole antifungals are coadministered with ODEFSEY.
Glucocorticoid (systemic): dexamethasone (more than a single dose)	↓ RPV	Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.
H2-Receptor Antagonists: cimetidine famotidine nizatidine ranitidine	↔  RPVcd (famotidine taken 12 hours before RPV or 4 hours after RPV) ↓ RPVcd (famotidine taken 2 hours before RPV)	Administer H2-receptor antagonists at least 12 hours before or at least 4 hours after ODEFSEY.
Herbal Products: St. John’s wort (Hypericum perforatum)	↓ RPV	Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.
Macrolide or Ketolide Antibiotics: clarithromycin erythromycin telithromycin	↑ RPV ↔ clarithromycin ↔ erythromycin ↔ telithromycin	Where possible, alternatives such as azithromycin should be considered.
Narcotic Analgesics: methadone	↓R(-) methadonec ↓S(+) methadonec ↔RPVc ↔methadonec (when used with tenofovir)	No dosage adjustments are required when initiating coadministration of methadone with ODEFSEY. However, clinical monitoring is recommended, as methadone maintenance therapy may need to be adjusted in some patients.
Proton Pump Inhibitors: e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole	↓ RPV	Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.
aThis table is not all inclusive. bIncrease=↑; Decrease=↓; No Effect=↔ cThe interaction was evaluated in a clinical study. All other drug interactions shown are predicted. dThis interaction study has been performed with a dose higher than the recommended dose for RPV. The dosing recommendation is applicable to the recommended dose of RPV 25 mg once daily.

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.

Read the entire FDA prescribing information for Odefsey (Emtricitabine, Rilpivirine, and Tenofovir Alafenamide Fixed-dose Combination Tablets)

&Copy; Odefsey Patient Information is supplied by Cerner Multum, Inc. and Odefsey Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.