Odefsey

Name: Odefsey

Odefsey Overview

Odefsey is a prescription medication used to treat HIV (Human Immunodeficiency Virus).

It is a single product containing 3 medications: emtricitabine, rilpivirine, and tenofovir alafenamide. 

Odefsey belongs to a group of drugs called antivirals. These help to decrease the amount of HIV in the blood. 

This medication comes in a tablet and is typically taken once a day, with food. 

Common side effects include depression, insomnia, headache, and nausea. 

What is emtricitabine, rilpivirine, and tenofovir?

Emtricitabine, rilpivirine, and tenofovir are antiviral medicines that prevent human immunodeficiency virus (HIV) from multiplying in your body.

Emtricitabine, rilpivirine, and tenofovir is a combination medicine used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). This medicine is not a cure for HIV or AIDS.

This medicine is for use in adults and children who are at least 12 years old and who have never taken HIV medicines before.

Emtricitabine, rilpivirine, and tenofovir should not be taken together with other antiviral medications to treat HIV or AIDS.

Emtricitabine, rilpivirine, and tenofovir may also be used for purposes not listed in this medication guide.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Uses For Odefsey

Emtricitabine, rilpivirine, and tenofovir alafenamide combination is used to treat human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS). This medicine is usually given to patients who have not received any HIV treatment in the past.

This medicine will not cure HIV infection or AIDS. It works by lowering the amount of HIV in the blood and it will also help your immune system. This may help delay some of the medical conditions that usually result from AIDS or HIV disease. It will not keep you from spreading HIV to other people.

This medicine is available only with your doctor's prescription.

Proper Use of Odefsey

Take this medicine exactly as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

Keep taking this medicine for the full time of treatment, even if you begin to feel better. Do not stop taking it without checking first with your doctor. When your supply of the medicine is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of the medicine.

This medicine comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Take the tablet with food.

If you take antacids that contain aluminum, magnesium, or calcium, take the antacid at least 2 hours before or 4 hours after you take this medicine.

If you take a stomach medicine for heartburn or ulcers such as cimetidine, famotidine, nizatidine, or ranitidine, take the heartburn medicine at least 12 hours before or 4 hours after you take this medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For treatment of HIV infection:
      • Adults and children 12 years and older weighing 35 kilograms (kg) or more—One tablet once a day.
      • Children younger than 12 years or weighing less than 35 kg—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep the medicine in the original bottle that you were given at the pharmacy and keep it tightly closed.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of too much lactic acid in the blood (lactic acidosis) like fast breathing, fast heartbeat, a heartbeat that does not feel normal, very bad upset stomach or throwing up, feeling very sleepy, shortness of breath, feeling very tired or weak, very bad dizziness, feeling cold, or muscle pain or cramps.
  • Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Bone pain.
  • Muscle pain or weakness.
  • Pain in arms or legs.
  • This medicine may help the immune system work. If you have an infection that you did not know you had, it may show up when you take Odefsey. Tell your doctor right away if you notice any signs of infection like fever, sore throat, weakness, cough, or shortness of breath after you start this medicine.
  • Very bad skin and allergic reactions have happened with Odefsey. Skin reactions have happened along with fever or problems in body organs like the liver. Call your doctor right away if you have red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; sores in your mouth, throat, nose, or eyes; trouble swallowing; or signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

How do I store and/or throw out Odefsey?

  • Store in the original container at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Adverse Reactions

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

  • Severe Acute Exacerbations of Hepatitis B [See Warnings and Precautions (5.1)]
  • Skin and Hypersensitivity Reactions [See Warnings and Precautions (5.2)]
  • Depressive Disorders [See Warnings and Precautions (5.5)]
  • Hepatotoxicity [See Warnings and Precautions (5.6)]
  • Immune Reconstitution Syndrome [See Warnings and Precautions (5.7)]
  • New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.8)]
  • Lactic Acidosis/Severe Hepatomegaly with Steatosis [See Warnings and Precautions (5.9)]

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 (14.1)].

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* (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)†
Odefsey
(N=316)
FTC/RPV/TDF
(N=313)†
* a. Frequencies of adverse reactions are based on all adverse events attributed to study drugs by the investigator. † 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.
Headache 2% 1% 0 1%
Flatulence 1% <1% <1% 1%
Sleep Disturbances 2% 1% 0 <1%
Abnormal Dreams 1% 1% 0 2%
Diarrhea 1% 3% 1% 2%
Nausea 1% 1% 1% 1%

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 Week 48 Baseline Week 48 Baseline Week 48 Baseline Week 48
mg/dL Change*,† mg/dL Change*,† mg/dL Change*,† mg/dL Change*,†
* The change from baseline is the mean of within-subject changes from baseline for subjects with both baseline and Week 48 values. † Subjects who received lipid-lowering agents during the treatment period were excluded. ‡ [n=296] for Odefsey group in Study 1160 for LDL-Cholesterol (fasted)
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 +1 118‡ -1‡ 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

Adverse Reactions in Clinical Trials of RPV-Containing Regimens in Treatment-Naïve Adult Subjects with HIV-1 Infection

In pooled 96-week trials of antiretroviral treatment-naïve 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-Naïve Adult Subjects with HIV-1 Infection

In pooled 48-week trials of antiretroviral treatment-naïve 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 (14)]. Antiretroviral treatment-naïve 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-naïve HIV-1 infected adults treated with FTC+TAF with EVG+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 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.

Bone Mineral Density Effects

In the pooled analysis of two 48-week trials of antiretroviral treatment-naïve 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-naïve 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-naïve 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-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.

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

Odefsey Description

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.

Each tablet contains 200 mg of FTC, 25 mg of RPV (equivalent to 27.5 of rilpivirine hydrochloride) and 25 mg of TAF (equivalent to 28 mg of tenofovir alafenamide fumarate) and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 20, and povidone. The tablets are film-coated with a coating material containing iron oxide black, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.

Emtricitabine: The chemical name of FTC is 4-amino-5-fluoro-1-(2R-hydroxymethyl-1,3-oxathiolan-5S-yl)-(1H)-pyrimidin-2-one. FTC is the (-)enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5 position.

FTC has a molecular formula of C8H10FN3O3S and a molecular weight of 247.24 and has the following structural formula:

FTC is a white to off-white powder with a solubility of approximately 112 mg per mL in water at 25 °C.

Rilpivirine: The chemical name of rilpivirine hydrochloride drug substance is 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile monohydrochloride. Its molecular formula is C22H18N6 ∙ HCl and its molecular weight is 402.88. Rilpivirine hydrochloride has the following structural formula:

Rilpivirine hydrochloride is a white to almost white powder. Rilpivirine hydrochloride is practically insoluble in water over a wide pH range.

Tenofovir Alafenamide: The chemical name of tenofovir alafenamide fumarate drug substance is L-alanine, N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester, (2E)-2-butenedioate (2:1).

Tenofovir alafenamide fumarate has an empirical formula of C21H29O5N6P∙½(C4H4O4) and a formula weight of 534.50 and has the following structural formula:

Tenofovir alafenamide fumarate is a white to off-white or tan powder with a solubility of 4.7 mg per mL in water at 20 °C.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Post-treatment Acute Exacerbation of Hepatitis B in Patients with HBV Coinfection

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued products containing FTC and/or TDF, and may likewise occur with discontinuation of Odefsey [see Warnings and Precautions (5.1)]. Advise the patient to not discontinue Odefsey without first informing their healthcare provider.

Severe Skin Reactions and Hypersensitivity

Inform patients that skin reactions ranging from mild to severe, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported with RPV-containing products. Instruct patients to immediately stop taking Odefsey and seek medical attention if they develop a rash associated with any of the following symptoms: fever, blisters, mucosal involvement, eye inflammation (conjunctivitis), severe allergic reaction causing swelling of the face, eyes, lips, mouth, tongue or throat which may lead to difficulty swallowing or breathing, and any signs and symptoms of liver problems, as they may be a sign of a more serious reaction. Patients should understand that if severe rash occurs, they will be closely monitored, laboratory tests will be performed and appropriate therapy will be initiated [see Warnings and Precautions (5.2)].

Drug Interactions

Odefsey may interact with many drugs and is not recommended to be coadministered with numerous drugs. Advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St. John's wort [see Contraindications (4), Warnings and Precautions (5.3) and Drug Interactions (7)].

Depressive Disorders

Inform patients that depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) have been reported with RPV. Inform patients to seek immediate medical evaluation if they experience depressive symptoms [see Warnings and Precautions (5.5)].

Hepatotoxicity

Inform patients that hepatotoxicity has been reported with RPV, therefore, it is important to inform the healthcare professional if patients have underlying hepatitis B or C or elevations in liver-associated tests prior to treatment [see Dosage and Administration (2.1) and Warnings and Precautions (5.6)].

Immune Reconstitution Syndrome

Advise patients to inform their healthcare provider immediately of any symptoms of infection, as in some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started [see Warnings and Precautions (5.7)].

New Onset or Worsening Renal Impairment

Advise patients to avoid taking Odefsey with concurrent or recent use of nephrotoxic agents. Renal impairment, including cases of acute renal failure, has been reported in association with the use of tenofovir prodrugs [see Warnings and Precautions (5.8)].

Lactic Acidosis and Severe Hepatomegaly

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of drugs similar to Odefsey. Advise patients to stop taking Odefsey if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.9)].

Missed Dosage

Inform patients that it is important to take Odefsey on a regular dosing schedule with a meal and to avoid missing doses, as it can result in development of resistance [see Dosage and Administration (2.2)].

Pregnancy Registry

Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnant women exposed to Odefsey [see Use in Specific Populations (8.1)].

Lactation

Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk [see Use in Specific Populations (8.2)].

Odefsey is a trademark of Gilead Sciences, Inc., or its related companies. All other trademarks referenced herein are the property of their respective owners.

Patient Information
Odefsey® (oh-DEF-see)
(emtricitabine, rilpivirine and tenofovir alafenamide)
tablets
This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 08/2017  
Important: Ask your healthcare provider or pharmacist about medicines that should not be taken with Odefsey. For more information, see "What should I tell my healthcare provider before taking Odefsey?"

What is the most important information I should know about Odefsey?

Odefsey can cause serious side effects, including:
Worsening of Hepatitis B virus infection. Odefsey is not for use to treat chronic hepatitis B virus (HBV) 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.
For more information about side effects, see "What are the possible side effects of Odefsey?"
What is Odefsey?
Odefsey is a prescription medicine that is used to treat Human Immunodeficiency Virus-1 (HIV-1) in people 12 years of age and older:
  • 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 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).
Who should not take Odefsey?
Do not take Odefsey if you also take a medicine that contains:
  • carbamazepine (CARBATROL®, EPITOL®, EQUETRO®, TEGRETOL®, TEGRETOL-XR®, TERIL®)
  • dexamethasone (OZURDEX®, MAXIDEX®, DECADRON®, BAYCADRON™)
  • dexlansoprazole (DEXILANT®)
  • esomeprazole (NEXIUM®, VIMOVO®)
  • lansoprazole (PREVACID®)
  • omeprazole (PRILOSEC®, ZEGERID®)
  • oxcarbazepine (TRILEPTAL®)
  • pantoprazole sodium (PROTONIX®)
  • phenobarbital (LUMINAL®)
  • phenytoin (DILANTIN®, DILANTIN-125®, PHENYTEK®)
  • rabeprazole (ACIPHEX®)
  • rifampin (RIFADIN®, RIFAMATE®, RIFATER®, RIMACTANE®)
  • rifapentine (PRIFTIN®)
  • St. John's wort (Hypericum perforatum) or a product that contains St. John's wort

What should I tell my healthcare provider before taking Odefsey?

Before taking Odefsey, tell your healthcare provider about all your medical conditions, including if you:
  • have liver problems, including hepatitis B or C virus infection
  • have kidney problems
  • have a history of depression or suicidal thoughts
  • are pregnant or plan to become pregnant. It is not known if Odefsey can harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with Odefsey.
    Pregnancy Registry: There is a pregnancy registry for women who take Odefsey during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry.
  • are breastfeeding or plan to breastfeed. Do not breastfeed if you take Odefsey.
    • You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.
    • At least one of the medicines in Odefsey can pass to your baby in your breast milk. It is not known if the other medicines in Odefsey can pass into your breast milk.
    Talk with your healthcare provider about the best way to feed your baby during treatment with Odefsey.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Some medicines may interact with Odefsey. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
  • You can ask your healthcare provider or pharmacist for a list of medicines that interact with Odefsey.
  • Do not start a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take Odefsey with other medicines.
How should I take Odefsey?
  • Take Odefsey exactly as your healthcare provider tells you to take it. Odefsey is taken by itself (not with other HIV-1 medicines) to treat HIV-1 infection.
  • Take Odefsey 1 time each day with a meal.
  • Do not change your dose or stop taking Odefsey without first talking with your healthcare provider. Stay under a healthcare provider's care during treatment with Odefsey.
  • Do not miss a dose of Odefsey.
  • If you take too much Odefsey, call your healthcare provider or go to the nearest hospital emergency room right away.
  • When your Odefsey supply starts to run low, get more from your healthcare provider or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to Odefsey and become harder to treat.

What are the possible side effects of Odefsey?

Odefsey may cause serious side effects, including:
  • See "What is the most important information I should know about Odefsey?"
  • Severe skin rash and allergic reactions. Skin rash is a common side effect of Odefsey. Rash can be serious. Call your healthcare provider right away if you get a rash. In some cases, rash and allergic reaction may need to be treated in a hospital.
    If you get a rash with any of the following symptoms, stop taking Odefsey and call your healthcare provider or get medical help right away:
  • fever
  • skin blisters
  • mouth sores
  • redness or swelling of the eyes (conjunctivitis)
  • swelling of the face, lips, mouth, or throat
  • trouble breathing or swallowing
  • pain on the right side of the stomach (abdominal) area
  • dark "tea colored" urine
  • Depression or mood changes. Tell your healthcare provider right away if you have any of the following symptoms:
    • feel sad or hopeless
    • feel anxious or restless
    • have thoughts of hurting yourself (suicide) or have tried to hurt yourself
  • Change in liver enzymes. People with a history of hepatitis B or C virus infection or who have certain liver enzyme changes may have an increased risk of developing new or worsening liver problems during treatment with Odefsey. Liver problems can also happen during treatment with Odefsey in people without a history of liver disease. Your healthcare provider may need to do tests to check your liver enzymes before and during treatment with Odefsey.
  • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having any new symptoms after starting your HIV-1 medicine.
  • New or worse kidney problems, including kidney failure. Your healthcare provider should do blood and urine tests to check your kidneys before you start and during treatment with Odefsey. Your healthcare provider may tell you to stop taking Odefsey if you develop new or worse kidney problems.
  • Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat.
  • Severe liver problems. In rare cases, severe liver problems can happen that can lead to death. Tell your healthcare provider right away if you get these symptoms: skin or the white part of your eyes turns yellow, dark "tea-colored" urine, light-colored stools, loss of appetite for several days or longer, nausea, or stomach-area pain.
The most common side effects of Odefsey are headache and problems sleeping.
These are not all the possible side effects of Odefsey.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Odefsey?
  • Store Odefsey below 86°F (30°C).
  • Keep Odefsey in its original container.
  • Keep the container tightly closed.
Keep Odefsey and all medicines out of reach of children.
General information about the safe and effective use of Odefsey.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Odefsey for a condition for which it was not prescribed. Do not give Odefsey to other people, even if they have the same symptoms you have. It may harm them.
You can ask your healthcare provider or pharmacist for information about Odefsey that is written for health professionals.
For more information, call 1-800-445-3235 or go to www.Odefsey.com.
What are the ingredients in Odefsey?
Active ingredients: emtricitabine, rilpivirine, and tenofovir alafenamide
Inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 20, and povidone. The tablet film coating contains iron oxide black, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide
Manufactured and distributed by: Gilead Sciences, Inc. Foster City, CA 94404
Odefsey is a trademark of Gilead Sciences, Inc., or its related companies. All other trademarks referenced herein are the property of their respective owners.
© 2017 Gilead Sciences, Inc. All rights reserved.
208351-GS-002

Odefsey side effects

Get emergency medical help if you have signs of an allergic reaction to Odefsey: hives, blistering skin rash with fever; mouth sores, eye redness; difficulty breathing; swelling of your face, lips, tongue, or throat.

Some people develop lactic acidosis while taking HIV medication. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Call your doctor at once if you have:

  • confusion, severe depression, unusual thoughts or behavior, suicidal thoughts or actions;

  • increased thirst and urination, loss of appetite, weakness, constipation;

  • kidney problems - little or no urinating, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath;

  • liver problems - swelling around your midsection, upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

  • signs of inflammation in your body - swollen glands, flu symptoms, easy bruising or bleeding, severe tingling or numbness, muscle weakness, upper stomach pain, jaundice (yellowing of the skin or eyes), chest pain, new or worsening cough with fever, trouble breathing;

Odefsey may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment. Tell your doctor if you have:

  • signs of a new infection - fever, night sweats, swollen glands, diarrhea, weight loss;

  • chest pain (especially when you breathe), dry cough, wheezing;

  • cold sores, sores on your genital or anal area;

  • feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

  • trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common Odefsey side effects may include:

  • headache, dizziness, tiredness;

  • depressed mood, sleep problems (insomnia), strange dreams;

  • rash;

  • nausea, diarrhea; or

  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

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.

For Healthcare Professionals

Applies to emtricitabine / rilpivirine / tenofovir alafenamide: oral tablet

General

During clinical studies, 550 antiretroviral therapy-naive patients received rilpivirine in combination with emtricitabine-tenofovir disoproxil fumarate (DF). The most common side effects were depression/depressive disorders, nausea, dizziness, abnormal dreams, headache, diarrhea, and insomnia. Treatment was discontinued due to side effects, regardless of severity, in 2% of patients taking rilpivirine in combination with emtricitabine-tenofovir DF. The most common side effects leading to discontinuation were psychiatric disorders. In virologically-suppressed patients switching to emtricitabine/rilpivirine/tenofovir DF, the most common side effects were fatigue, diarrhea, nausea, and insomnia.

The manufacturer product information for emtricitabine, rilpivirine, and tenofovir DF should be consulted.[Ref]

Hepatic

Increased ALT (grade 1: 19%; grade 2: 5%; grade 3: 1%; grade 4: 1%), AST (grade 1: 16%; grade 2: 4%; grade 3: 2%; grade 4: 1%), and total bilirubin (grade 1: 6%; grade 2: 3%; grade 3: 1%) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HBV and HIV-1 after discontinuation of emtricitabine or tenofovir DF and were associated with liver failure and liver decompensation in some emtricitabine-treated patients.

The incidence of hepatic enzyme elevation was higher in patients receiving rilpivirine who were coinfected with hepatitis B or C than in patients without coinfection.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Hepatic steatosis and hepatitis have also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine-tenofovir DF plus rilpivirine:
-Very common (10% or more): Increased ALT (up to 19%), increased AST (up to 16%)
-Common (1% to 10%): Increased total bilirubin

Emtricitabine and/or tenofovir DF:
-Frequency not reported: Severe hepatomegaly with steatosis, severe acute exacerbations of hepatitis B

Emtricitabine:
-Common (1% to 10%): Elevated serum AST and/or elevated serum ALT, hyperbilirubinemia
-Frequency not reported: Liver failure, liver decompensation

Rilpivirine:
-Very common (10% or more): Increased transaminases (AST and/or ALT)
-Common (1% to 10%): Cholecystitis, cholelithiasis, increased bilirubin
-Frequency not reported: Hepatic enzyme elevation, hepatotoxicity, drug-induced acute allergic hepatitis

Tenofovir DF:
-Common (1% to 10%): Increased transaminases (AST and/or ALT)
-Rare (less than 0.1%): Hepatic steatosis, hepatitis
-Frequency not reported: Lactic acidosis/severe hepatomegaly with steatosis
-Postmarketing reports: Elevated liver enzymes (primarily AST, ALT, GGT)[Ref]

Metabolic

Emtricitabine-tenofovir DF plus rilpivirine:
-Very common (10% or more): Increased fasted total cholesterol (up to 14%), increased fasted low-density lipoprotein (LDL) cholesterol (up to 13%)
-Common (1% to 10%): Increased fasted triglycerides, hypophosphatemia

Emtricitabine and tenofovir alafenamide:
-Frequency not reported: Increased total cholesterol, increased LDL cholesterol, increased high-density lipoprotein (HDL) cholesterol, increased triglycerides

Emtricitabine and/or tenofovir DF:
-Frequency not reported: Increased alkaline phosphatase, increased or decreased serum glucose, lactic acidosis

Emtricitabine:
-Common (1% to 10%): Hyperglycemia, hypertriglyceridemia

Rilpivirine:
-Very common (10% or more): Increased fasted total cholesterol, increased fasted LDL cholesterol
-Common (1% to 10%): Decreased appetite, increased fasted triglycerides

Tenofovir DF:
-Very common (10% or more): Hypophosphatemia
-Uncommon (0.1% to 1%): Hypokalemia
-Rare (less than 0.1%): Lactic acidosis

Antiretroviral therapy:
-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased blood lipid levels, increased glucose levels[Ref]

Increased fasted total cholesterol (grade 1: 14%; grade 2: 6%; grade 3: less than 1%), fasted LDL cholesterol (grade 1: 13%; grade 2: 5%; grade 3: 1%) and fasted triglycerides (grade 2: 1%; grade 3: 1%) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

In clinical trials, the following mean increases were reported in antiretroviral therapy-naive patients after using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat for 48 weeks: total cholesterol increased by 30 mg/dL, LDL cholesterol by 15 mg/dL, HDL cholesterol by 7 mg/dL, and triglycerides by 29 mg/dL.

Increased alkaline phosphatase (greater than 550 units/L) and increased or decreased serum glucose (less than 40 or greater than 250 mg/dL) have been reported with emtricitabine or tenofovir DF.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Hypokalemia and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Lactic acidosis, hypokalemia, and hypophosphatemia have also been reported during postmarketing experience with tenofovir DF.[Ref]

Psychiatric

Depression, insomnia, and abnormal dreams have been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Anxiety has been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.

During Phase 3 trials through 96 weeks, depressive disorders (regardless of causality, severity) were reported in 9% of patients receiving rilpivirine.[Ref]

Emtricitabine/rilpivirine/tenofovir DF:
-Common (1% to 10%): Insomnia

Emtricitabine-tenofovir DF plus rilpivirine:
-Common (1% to 10%): Depression, depressive disorders (reported as depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation), insomnia, abnormal dreams

Emtricitabine and/or tenofovir DF:
-Very common (10% or more): Depression, insomnia, abnormal dreams
-Common (1% to 10%): Anxiety

Emtricitabine:
-Common (1% to 10%): Insomnia, abnormal dreams

Rilpivirine:
-Very common (10% or more): Insomnia
-Common (1% to 10%): Depressive disorders, anxiety, abnormal dreams, depression, sleep disorders, depressed mood[Ref]

Dermatologic

During phase 3 trials, 1% of patients using rilpivirine with emtricitabine and tenofovir DF reported at least grade 2 therapy-related rashes; most rashes were grade 1 or 2 and developed in the first 4 to 6 weeks of therapy.

Rash has been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF.

Rash has also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine/rilpivirine/tenofovir DF:
-Postmarketing reports: Severe skin and hypersensitivity reactions (including drug reaction with eosinophilia and systemic symptoms [DRESS]), severe skin reactions with systemic symptoms (including rashes with fever, blisters, conjunctivitis, angioedema, elevated liver function tests, and/or eosinophilia)

Emtricitabine-tenofovir DF plus rilpivirine:
-Common (1% to 10%): Rash

Emtricitabine and tenofovir DF:
-Very common (10% or more): Rash
-Frequency not reported: Lipodystrophy

Emtricitabine:
-Common (1% to 10%): Vesiculobullous rash, pustular rash, maculopapular rash, rash, pruritus, urticaria, skin discoloration (palmar-plantar hyperpigmentation)
-Postmarketing reports: Angioedema

Rilpivirine:
-Common (1% to 10%): Rash
-Postmarketing reports: Severe skin and hypersensitivity reactions (including DRESS)

Tenofovir DF:
-Very common (10% or more): Rash
-Postmarketing reports: Angioedema[Ref]

Nervous system

Headache and dizziness have been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Paresthesia and peripheral neuropathy (including peripheral neuritis and neuropathy) have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.[Ref]

Emtricitabine-tenofovir DF plus rilpivirine:
-Common (1% to 10%): Headache, dizziness

Emtricitabine and/or tenofovir DF:
-Very common (10% or more): Headache, dizziness
-Common (1% to 10%): Paresthesia, peripheral neuropathy (including peripheral neuritis, neuropathy)

Emtricitabine:
-Very common (10% or more): Headache
-Common (1% to 10%): Dizziness

Rilpivirine:
-Very common (10% or more): Headache, dizziness
-Common (1% to 10%): Somnolence

Tenofovir DF:
-Very common (10% or more): Dizziness
-Common (1% to 10%): Headache[Ref]

Renal

Emtricitabine-tenofovir DF plus rilpivirine:
-Common (1% to 10%): Increased creatinine

Emtricitabine and tenofovir alafenamide:
-Frequency not reported: Increased serum creatinine, decreased urine protein-to-creatinine ratio (UPCR), worsening renal function

Rilpivirine:
-Common (1% to 10%): Membranous glomerulonephritis, mesangioproliferative glomerulonephritis, nephrolithiasis
-Frequency not reported: Increased serum creatinine, decreased estimated glomerular filtration rate (eGFR)
-Postmarketing reports: Nephrotic syndrome

Tenofovir DF:
-Uncommon (0.1% to 1%): Increased creatinine
-Rare (less than 0.1%): Renal failure (acute and chronic), acute tubular necrosis, proximal renal tubulopathy (including Fanconi syndrome), nephrogenic diabetes insipidus
-Frequency not reported: New onset or worsening renal impairment
-Postmarketing reports: Renal insufficiency, interstitial nephritis (including acute cases)

Tenofovir prodrugs:
-Frequency not reported: Renal impairment (including renal failure, Fanconi syndrome)[Ref]

Increased creatinine (grade 1: 6%; grade 2: 1%; grade 3: less than 1%) has been reported with emtricitabine-tenofovir DF plus rilpivirine.

In 2 trials in antiretroviral therapy-naive HIV-1-infected patients (median eGFR 115 mL/min at baseline) using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine increased by 0.1 mg/dL from baseline to week 48; median UPCR was 44 mg/g at baseline and at week 48. In a trial in virologically-suppressed tenofovir DF-treated patients (mean eGFR 112 mL/min at baseline) who switched to emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine was similar to baseline; median UPCR was 61 mg/g at baseline and 46 mg/g at week 48. In a trial in renal dysfunction patients (baseline eGFR 30 to 69 mL/min) using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine was 1.5 mg/dL at baseline and week 24; median UPCR was 161 mg/g at baseline and 93 mg/g at week 24.

During phase 3 trials, an increase in serum creatinine and decrease in eGFR were seen over 96 weeks of therapy with rilpivirine. Most of these changes occurred within the first 4 weeks of therapy, with a mean change of 0.1 mg/dL (range: -0.3 to 0.6 mg/dL) for creatinine and -13.3 mL/min/1.73 m2 (range: -63.7 to 40.1 mL/min/1.73 m2) for eGFR observed after 96 weeks of therapy. In subjects with mild or moderate baseline renal dysfunction, the serum creatinine increase observed was similar to that seen in subjects with normal renal function. These changes were not considered clinically relevant and no subject discontinued therapy due to increases in serum creatinine.

Proximal renal tubulopathy generally resolved or improved after tenofovir DF was stopped; however, decreased CrCl did not completely resolve in some patients after stopping the drug. Rhabdomyolysis, osteomalacia, bone abnormalities (infrequently contributing to fractures), hypokalemia, muscular weakness, myopathy, and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, nephrogenic diabetes insipidus, and acute tubular necrosis have also been reported during postmarketing experience with tenofovir DF.[Ref]

Gastrointestinal

Emtricitabine/rilpivirine/tenofovir DF:
-Common (1% to 10%): Diarrhea, nausea

Emtricitabine-tenofovir DF plus rilpivirine:
-Common (1% to 10%): Nausea, increased pancreatic amylase
-Uncommon (0.1% to 1%): Increased lipase

Emtricitabine and tenofovir alafenamide:
-Common (1% to 10%): Nausea

Emtricitabine and/or tenofovir DF:
-Very common (10% or more): Diarrhea, nausea
-Common (1% to 10%): Abdominal pain, dyspepsia, vomiting
-Frequency not reported: Increased pancreatic amylase, increased serum amylase, increased lipase

Emtricitabine:
-Very common (10% or more): Diarrhea, nausea
-Common (1% to 10%): Elevated amylase (including elevated pancreatic amylase), elevated serum lipase, vomiting, abdominal pain, dyspepsia

Rilpivirine:
-Very common (10% or more): Nausea, increased pancreatic amylase
-Common (1% to 10%): Vomiting, diarrhea, abdominal discomfort, abdominal pain, increased lipase, dry mouth

Tenofovir DF:
-Very common (10% or more): Diarrhea, vomiting, nausea
-Common (1% to 10%): Abdominal pain, abdominal distension, flatulence
-Uncommon (0.1% to 1%): Pancreatitis
-Postmarketing reports: Increased amylase[Ref]

In clinical trials, nausea was the most common side effect reported in antiretroviral therapy-naive HIV-1-infected patients using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat.

Diarrhea and nausea have been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Abdominal pain, dyspepsia, and vomiting have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.

Increased pancreatic amylase (greater than 2 times upper limit of normal [ULN]), serum amylase (greater than 175 units/L), and lipase (greater than 3 times ULN) have been reported with emtricitabine and/or tenofovir DF.

Pancreatitis and abdominal pain have also been reported during postmarketing experience with tenofovir DF.[Ref]

Other

Emtricitabine/rilpivirine/tenofovir DF:
-Common (1% to 10%): Fatigue
-Postmarketing reports: Weight increased

Emtricitabine and/or tenofovir DF:
-Very common (10% or more): Fatigue
-Common (1% to 10%): Fever, pain

Emtricitabine:
-Common (1% to 10%): Pain, asthenia

Rilpivirine:
-Common (1% to 10%): Fatigue
-Postmarketing reports: Weight increased

Tenofovir DF:
-Very common (10% or more): Asthenia
-Frequency not reported: Higher 1,25 vitamin D levels

Antiretroviral therapy:
-Frequency not reported: Increased weight[Ref]

Other side effects have included fatigue in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Fever and pain have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.

Asthenia has also been reported during postmarketing experience with tenofovir DF.[Ref]

Hypersensitivity

Emtricitabine/rilpivirine/tenofovir DF:
-Postmarketing reports: Severe skin and hypersensitivity reactions (including DRESS)

Emtricitabine:
-Common (1% to 10%): Allergic reaction

Rilpivirine:
-Postmarketing reports: Severe skin and hypersensitivity reactions (including DRESS)

Tenofovir DF:
-Postmarketing reports: Allergic reaction (including angioedema)[Ref]

Immunologic

Emtricitabine, rilpivirine, and/or tenofovir DF:
-Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Emtricitabine:
-Postmarketing reports: Immune reconstitution syndrome

Rilpivirine:
-Uncommon (0.1% to 1%): Immune reactivation syndrome

Tenofovir DF:
-Postmarketing reports: Immune reconstitution syndrome[Ref]

Musculoskeletal

Emtricitabine and tenofovir alafenamide:
-Very common (10% or more): Decreased bone mineral density (BMD)
-Uncommon (0.1% to 1%): Fractures (excluding fingers and toes)
-Frequency not reported: Increased biochemical markers of bone metabolism, increased BMD

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Arthralgia, back pain, myalgia
-Frequency not reported: Increased creatine kinase

Emtricitabine:
-Very common (10% or more): Elevated creatine kinase

Tenofovir DF:
-Uncommon (0.1% to 1%): Rhabdomyolysis, muscular weakness
-Rare (less than 0.1%): Myopathy
-Frequency not reported: Decreased BMD, increased biochemical markers of bone metabolism, bone abnormalities
-Postmarketing reports: Osteomalacia (manifested as bone pain and which may contribute to fractures)

Combination antiretroviral therapy:
-Frequency not reported: Osteonecrosis[Ref]

In clinical trials, a significant decline in BMD was seen in 15% of therapy-naive HIV-1-infected patients using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat. In virologically-suppressed tenofovir DF-treated patients who switched to emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean BMD increased between baseline and week 48; decreased BMD was also reported.

Arthralgia, back pain, and myalgia have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.

Increased creatine kinase (males: greater than 990 units/L; females: greater than 845 units/L) has been reported with emtricitabine or tenofovir DF.

Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy may occur due to proximal renal tubulopathy.

Rhabdomyolysis, muscular weakness, and myopathy have also been reported during postmarketing experience with tenofovir DF.[Ref]

Respiratory

Nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, increased cough, and rhinitis have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.[Ref]

Emtricitabine or tenofovir DF:
-Common (1% to 10%): Nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, increased cough, rhinitis

Tenofovir DF:
-Postmarketing reports: Dyspnea[Ref]

Hematologic

Decreased neutrophils (less than 750/mm3) have been reported with emtricitabine or tenofovir DF.[Ref]

Emtricitabine or tenofovir DF:
-Frequency not reported: Decreased neutrophils

Emtricitabine:
-Common (1% to 10%): Neutropenia
-Uncommon (0.1% to 1%): Anemia

Rilpivirine:
-Common (1% to 10%): Decreased white blood cell count, decreased hemoglobin, decreased platelet count[Ref]

Genitourinary

Increased glycosuria (3+ or greater) and hematuria (greater than 75 red blood cells/high power field) have been reported with emtricitabine or tenofovir DF.

Proteinuria has also been reported during postmarketing experience with tenofovir DF.[Ref]

Emtricitabine or tenofovir DF:
-Frequency not reported: Increased glycosuria, increased hematuria

Tenofovir DF:
-Uncommon (0.1% to 1%): Proteinuria
-Postmarketing reports: Polyuria[Ref]

Endocrine

Rilpivirine:
-Frequency not reported: Decreased basal cortisol, decreased adrenocorticotropic hormone (ACTH)-stimulated cortisol levels, adrenal insufficiency, abnormal 250 mcg ACTH stimulation test

Tenofovir DF:
-Frequency not reported: Higher serum parathyroid hormone levels[Ref]

In the pooled phase 3 trials, at week 96, there was an overall mean change from baseline in basal cortisol of -19.1 nmol/L (-0.69 mcg/dL) in the rilpivirine group, and of -0.6 nmol/L (-0.02 mcg/dL) in the efavirenz group. At week 96, the mean change from baseline in ACTH-stimulated cortisol levels was lower in the rilpivirine group (+18.4 nmol/L) than in the efavirenz group (+54.1 nmol/L). Mean values for both basal and ACTH-stimulated cortisol values at week 96 were within the normal range.

In the rilpivirine group, 43 of 588 patients with normal 250 mcg ACTH stimulation test at baseline developed abnormal 250 mcg ACTH stimulation test (peak cortisol level less than 18.1 mcg/dL) during the trial versus 18 of 561 patients in the efavirenz group. Abnormal 250 mcg ACTH stimulation test at week 96 was seen in 14 of the 43 rilpivirine patients and 9 of the 18 efavirenz patients. Clinical significance of abnormal 250 mcg ACTH stimulation tests (or the higher rate in the rilpivirine group) has not been established.

Overall, there were no serious side effects, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency.[Ref]

Some side effects of Odefsey may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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