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Odefsey Side Effects

Generic name: emtricitabine / rilpivirine / tenofovir alafenamide

Medically reviewed by Drugs.com. Last updated on Oct 2, 2024.

Note: This document provides detailed information about Odefsey Side Effects associated with emtricitabine / rilpivirine / tenofovir alafenamide. Some dosage forms listed on this page may not apply specifically to the brand name Odefsey.

Applies to emtricitabine / rilpivirine / tenofovir alafenamide: oral tablet.

Important warnings This medicine can cause some serious health issues

Oral route (tablet)

Emtricitabine/rilpivirine/tenofovir alafenamide is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of emtricitabine/rilpivirine/tenofovir alafenamide have not been established in patients coinfected with human immunodeficiency virus-1 (HIV-1) and HBV.

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with emtricitabine / rilpivirine / tenofovir alafenamide.

Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several moths in patients who are coinfected with HIV-1 and HBV and discontinue emtricitabine / rilpivirine / tenofovir alafenamide.

If appropriate, initiation of antihepatitis B therapy may be warranted.

Precautions

It is very important that your doctor check your or your child's progress at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

This medicine does not decrease the risk of transmitting HIV infection to others through sexual contact or by contamination through blood. HIV may be acquired from or spread to others through infected body fluids, including blood, vaginal fluid, or semen. If you are infected, it is best to avoid any sexual activity involving an exchange of body fluids with other people. If you do have sex, always wear (or have your partner wear) a condom (“rubber”). Only use condoms made of latex or polyurethane and use them every time you have contact with semen, vaginal secretions, or blood. Also, do not share needles or equipment with anyone or use dirty needles. If you have any questions about this, check with your doctor.

This medicine should not be used together with dexamethasone (Decadron®), certain seizure medicines (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, Dilantin®, Tegretol®, Trileptal®), medicines for tuberculosis (eg, rifampin, rifapentine, Priftin®, Rifadin®, Rimactane®), certain stomach medicines (eg, dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, Aciphex®, Dexilant®, Nexium®, Prevacid®, Prilosec®), or St. John's wort.

The medicines in this combination tablet are also available as Atripla®, Edurant®, Emtriva®, Stribild®, Truvada®, and Viread®. Do not take the emtricitabine, rilpivirine, and tenofovir alafenamide combination with any of these medicines.

This medicine may cause a rare, but serious, unwanted effect called lactic acidosis (too much acid in the blood). Call your doctor right away if you have abdominal or stomach discomfort, decreased appetite, diarrhea, fast, shallow breathing, general feeling of discomfort, muscle pain or cramping, nausea, sleepiness, or unusual tiredness or weakness.

This medicine may cause rare, but serious, liver problems. This is more common in patients with a history of hepatitis B or C infection or those who already have liver disease. Check with your doctor right away if you have clay-colored stools, dark urine, decreased appetite, fever, headache, itching, nausea and vomiting, skin rash, stomach pain or tenderness, swelling of the feet or lower legs, unusual tiredness or weakness, or yellow eyes or skin.

This medicine may cause serious types of allergic reactions, including skin reactions and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Check with your doctor right away if you have blistering, peeling, or loosening of the skin, large, hive-like swelling of the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals, severe acne or skin rash, sores or ulcers on the skin, or fever or chills with this medicine.

Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you or anyone in your family has ever had a heart rhythm problem such as QT prolongation.

Tell your doctor right away if you start to feel depressed or have thoughts about hurting yourself. Report any unusual thoughts or behavior that troubles you, especially if they are new or get worse quickly.

Your immune system may get stronger when you start using HIV medicines. Tell your doctor right away if you notice any changes in your health. Sometimes the immune system will start to fight infections that were hidden in your body, such as pneumonia, herpes, or tuberculosis. Autoimmune disorders such as Graves disease, polymyositis, and Guillain-Barré syndrome may also occur.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Serious side effects of Odefsey

Along with its needed effects, emtricitabine / rilpivirine / tenofovir alafenamide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking emtricitabine / rilpivirine / tenofovir alafenamide:

More common side effects

  • discouragement
  • feeling sad or empty
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • mental depression
  • thoughts of killing oneself
  • tiredness
  • trouble concentrating
  • trouble sleeping

Less common side effects

  • body aches or pain
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • chest pain
  • chills
  • cough
  • difficulty with breathing
  • ear congestion
  • fever
  • headache
  • loss of voice
  • runny or stuffy nose
  • sneezing
  • sore throat
  • tightness in the chest
  • unsteadiness or awkwardness
  • unusual tiredness or weakness
  • weakness in the arms, hands, legs, or feet

Incidence not known

  • agitation
  • bloating
  • bloody or cloudy urine
  • confusion
  • constipation
  • dark urine
  • decreased appetite
  • decreased urination
  • diarrhea
  • difficulty swallowing
  • dizziness
  • dry mouth
  • fast heartbeat
  • fast, shallow breathing
  • frequent urination
  • hostility
  • increased thirst
  • indigestion
  • irritability
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
  • light-colored stools
  • muscle pain or cramps
  • muscle tenderness, wasting, or weakness
  • nausea
  • pain in the stomach, side, or abdomen, possibly radiating to the back
  • rapid weight gain
  • seizures
  • skin rash, hives, itching
  • sleepiness
  • stomach discomfort
  • swelling of the face, ankles, hands, feet, or lower legs
  • unusual drowsiness, dullness, or feeling of sluggishness
  • vomiting
  • yellow eyes or skin

Other side effects of Odefsey

Some side effects of emtricitabine / rilpivirine / tenofovir alafenamide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common side effects

  • abnormal dreams

Less common side effects

  • back pain
  • belching
  • difficulty with moving
  • heartburn
  • pain in the joints
  • pain or tenderness around the eyes and cheekbones
  • stomach discomfort or upset

Incidence not known

  • lack or loss of strength

For healthcare professionals

Applies to emtricitabine / rilpivirine / tenofovir alafenamide: oral tablet.

General adverse events

The most common side effects reported with emtricitabine / rilpivirine / tenofovir alafenamide in virologically-suppressed patients with HIV-1 infection were headache and sleep disturbances.

During clinical studies, 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. 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, tenofovir alafenamide, and tenofovir DF should be consulted.[Ref]

Gastrointestinal

Emtricitabine / rilpivirine / tenofovir alafenamide:

Emtricitabine/rilpivirine/tenofovir DF:

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir DF:

Increased pancreatic amylase (greater than 2 times the upper limit of normal [2 x ULN]) and lipase (greater than 3 x ULN) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

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.

Increased amylase (greater than 2 x ULN) and lipase have been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF; lipase test was performed only for patients with serum amylase greater than 1.5 x ULN.

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 x ULN), serum amylase (greater than 175 units/L), and lipase (greater than 3 x ULN) have been reported with emtricitabine and/or tenofovir DF.[Ref]

Nervous system

Emtricitabine / rilpivirine / tenofovir alafenamide:

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir DF:

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]

Psychiatric

Emtricitabine / rilpivirine / tenofovir alafenamide:

Emtricitabine/rilpivirine/tenofovir DF:

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

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]

Musculoskeletal

Emtricitabine / rilpivirine / tenofovir alafenamide:

Emtricitabine/rilpivirine/tenofovir DF:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Tenofovir DF:

Combination antiretroviral therapy:

In 2 trials, BMD increased in patients who switched to emtricitabine / rilpivirine / tenofovir alafenamide and remained stable or decreased in patients who remained on emtricitabine/rilpivirine/tenofovir DF. BMD decreases occurred more often in patients using emtricitabine/rilpivirine/tenofovir DF than those using emtricitabine / rilpivirine / tenofovir alafenamide.

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 (at least 10 x ULN) has been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-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.[Ref]

Other

Emtricitabine / rilpivirine / tenofovir alafenamide:

Emtricitabine/rilpivirine/tenofovir DF:

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir DF:

Antiretroviral therapy:

In patients using emtricitabine / rilpivirine / tenofovir alafenamide from baseline to week 48, fasted total cholesterol, fasted HDL cholesterol, fasted LDL cholesterol, and fasted triglycerides increased in 1 trial and decreased in another trial; total cholesterol to HDL ratio increased in both trials. In patients using emtricitabine/rilpivirine/tenofovir DF from baseline to week 48, fasted total cholesterol and fasted HDL cholesterol did not change, fasted LDL cholesterol increased, fasted triglycerides decreased, and total cholesterol to HDL ratio increased in 1 trial while in another trial fasted total cholesterol, fasted HDL cholesterol, and fasted LDL cholesterol decreased, fasted triglycerides increased, and total cholesterol to HDL ratio did not change.

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.

Increased fasted total cholesterol (greater than 300 mg/dL), fasted LDL cholesterol (greater than 191 mg/dL), and fasted triglycerides (greater than 751 mg/dL) 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 fasted LDL cholesterol (greater than 190 mg/dL) and fasted total cholesterol (greater than 300 mg/dL) have been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF.

Increased alkaline phosphatase (greater than 550 units/L) has been reported with emtricitabine or tenofovir DF.

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.[Ref]

Renal

Emtricitabine / rilpivirine / tenofovir alafenamide:

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Rilpivirine:

Tenofovir DF:

Tenofovir prodrugs:

In 1 trial, baseline eGFR averaged 104 mL/min for patients who switched to emtricitabine / rilpivirine / tenofovir alafenamide from emtricitabine/rilpivirine/tenofovir DF; serum creatinine decreased by 0.02 mg/dL from baseline to week 48. In another trial, baseline eGFR averaged 110 mL/min for patients who switched to emtricitabine / rilpivirine / tenofovir alafenamide from emtricitabine/rilpivirine/tenofovir DF; serum creatinine increased by 0.1 mg/dL from baseline to week 48.

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

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 have occurred as a result of proximal renal tubulopathy.[Ref]

Dermatologic

Emtricitabine/rilpivirine/tenofovir DF:

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir alafenamide:

Tenofovir DF:

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.[Ref]

Hypersensitivity

Emtricitabine/rilpivirine/tenofovir DF:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir DF:

Hepatic

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir DF:

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.

Increased ALT (greater than 5 x ULN) and AST (greater than 5 x ULN) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

Increased ALT (greater than 5 x ULN) and AST (greater than 5 x ULN) have been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF.

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.[Ref]

Metabolic

Emtricitabine-tenofovir DF plus rilpivirine:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir DF:

Antiretroviral therapy:

Increased or decreased serum glucose (less than 40 or greater than 250 mg/dL) has 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 have occurred as a result of proximal renal tubulopathy.[Ref]

Immunologic

Emtricitabine, rilpivirine, and/or tenofovir DF:

Emtricitabine and/or tenofovir DF:

Emtricitabine:

Rilpivirine:

Tenofovir DF:

Combination antiretroviral therapy:

Genitourinary

Emtricitabine and tenofovir alafenamide:

Emtricitabine and/or tenofovir DF:

Tenofovir DF:

Increased urine RBC (hematuria; greater than 75 RBC/high power field) has been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF.

Increased glycosuria (3+ or greater) and hematuria (greater than 75 RBC/high power field) have been reported with emtricitabine or tenofovir DF.[Ref]

Respiratory

Emtricitabine and/or tenofovir DF:

Tenofovir DF:

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]

Hematologic

Emtricitabine or tenofovir DF:

Emtricitabine:

Rilpivirine:

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

Endocrine

Rilpivirine:

Tenofovir DF:

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]

See also:

References

1. Cerner Multum, Inc. "UK Summary of Product Characteristics."

2. Cerner Multum, Inc. "Australian Product Information."

3. (2011) "Product Information. Complera (emtricitabine/rilpivirine/tenofovir)." Gilead Sciences

4. (2016) "Product Information. Odefsey (emtricitabine/rilpivirine/tenofovir)." Gilead Sciences

5. Ahmed Y, Siddiqui W, Enoch CB, Albrecht H, Bookstaver PB (2012) "Rare case of rilpivirine-induced severe allergic hepatitis." J Antimicrob Chemother

Frequently asked questions

Further information

Odefsey side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.