Odefsey

The most common side effects of Odefsey include the following:

• trouble sleeping (insomnia)
• headache
• depression
• tiredness
• dizziness
• nausea
• stomach pain
• rash
• vomiting

This is not a complete list of Odefsey's side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Serious side effects have been reported with this medication, including the following:

• 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 doctor or get medical help right away:
  • fever
  • skin blisters
  • swelling of the face, lips, mouth, or throat
  • trouble breathing or swallowing
  • mouth sores
  • pain on the right side of the stomach (abdominal) area
  • redness or swelling of the eyes (conjunctivitis)
  • dark “tea colored” urine
• Depression or mood changes. Tell your healthcare provider right away if you have any of the following symptoms:
  • feeling sad or hopeless
  • feeling 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 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 if you start having new symptoms after starting your HIV medicine.
• A build-up of an acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take Odefsey or similar (nucleoside analogs) medicines. Lactic acidosis is a serious medical emergency that can lead to death.
  • Lactic acidosis can be hard to identify early, because the symptoms could seem like symptoms of other health problems. Call your healthcare provider right away if you get any of the following symptoms which could be signs of lactic acidosis:
    • feeling very weak or tired
    • have unusual (not normal) muscle pain
    • have trouble breathing
    • have stomach pain with nausea (feel sick to your stomach)
    • vomiting
    • feel cold, especially in your arms and legs
    • feel dizzy or lightheaded
    • have a fast or irregular heartbeat
• Severe liver problems. Severe liver problems may happen in people who take Odefsey. In some cases, these liver problems can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis). Call your healthcare provider right away if you get any of the following symptoms of liver problems:
  • your skin or the white part of your eyes turns yellow (jaundice)
  • light-colored bowel movements (stools) o nausea o dark “tea-colored” urine
  • loss of appetite o pain, aching, or tenderness on the right side of your stomach area

You may be more likely to get lactic acidosis or severe liver problems if you are female, very overweight (obese), or have been taking Odefsey or a similar medicine containing nucleoside analog for a long time. 

• 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. 
• New or worse kidney problems, including kidney failure, can happen in some people who take Odefsey. Your healthcare provider should do blood tests to check your kidneys before starting treatment with Odefsey. If you have had kidney problems in the past or need to take another medicine that can cause kidney problems, your healthcare provider may need to do blood tests to check your kidneys during your treatment with Odefsey.

Do not take this medication if you are:

• allergic to Odefsey or to any of its ingredients
• taking the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• taking the antimycobacterials rifampin or rifapentine
• taking proton pump inhibitors, such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
• taking the glucocorticoid systemic dexamethasone (more than a single dose)
• taking St. John's wort (Hypericum perforatum)

If you take Odefsey, you should not take:

• other medicines that contain tenofovir (Viread, Truvada, Stribild, Atripla)
• other medicines that contain emtricitabine or lamivudine (Emtriva, Combivir, Epivir or Epivir-HBV, Epzicom, Trizivir, Atripla, Truvada, Stribild)
• rilpivirine (Edurant)
• adefovir (Hepsera)

Tell your doctor if you are pregnant or plan to become pregnant.

There are insufficient human data on the use of this medication during pregnancy to inform a drug-associated risk of birth defects and miscarriage. 

There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.

You should not take this medicine if you are allergic to emtricitabine, rilpivirine, or tenofovir.

Do not take this medicine with other medicines that also contain emtricitabine, rilpivirine, tenofovir, adefovir, or lamivudine.

There are many other drugs that can make rilpivirine less effective and should not be used at the same time:

• dexamethasone;

• St. John's wort;

• tuberculosis medication--rifabutin, rifampin, rifapentine;

• seizure medicine--carbamazepine, oxcarbazepine, phenobarbital, phenytoin; or

• stomach acid reducers--dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• kidney disease;

• liver disease (including hepatitis B or C);

• a history of depression or mental illness;

• a personal or family history of Long QT syndrome; or

• osteoporosis, or osteopenia (low bone mineral density).

Some people taking tenofovir develop a serious condition called lactic acidosis. This may be more likely in women, in people who are overweight or have liver disease, and in people who have taken HIV/AIDS medication for a long time. Talk with your doctor about your risk.

HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection. Tell your doctor if you become pregnant during treatment. If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of the medicine on the baby.

Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

This medicine is not approved for use by anyone younger than 12 years old.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Always take this medicine with food.

If a child is using this medicine, tell your doctor if the child has any changes in weight. Doses are based on weight in children, and any changes may affect your child's dose.

While using this medicine, you may need frequent blood tests. Your bone density may also need to be tested.

If you have hepatitis B you may develop liver symptoms after you stop taking this medication, even months after stopping. Your doctor may want to check your liver function for several months after you stop using this medicine.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store in original container at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Be sure to take the medicine with a meal. If you are more than 12 hours late, skip the missed dose. Do not take extra medicine to make up the missed dose.

In the U.S.

• Odefsey

Available Dosage Forms:

• Tablet

Therapeutic Class: Antiretroviral Agent

Pharmacologic Class: Nucleoside Reverse Transcriptase Inhibitor

Odefsey is 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 [see Microbiology (12.4) and Clinical Studies (14)].

Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV

Patients with HIV-1 should be tested for the presence of hepatitis B virus (HBV) before initiating antiretroviral therapy [see Dosage and Administration (2.1)]. Odefsey is not approved for the treatment of chronic HBV infection, and the safety and efficacy of Odefsey have not been established in patients coinfected with HIV-1 and HBV.

Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing FTC and/or TDF, and may occur with discontinuation of Odefsey. Patients coinfected with HIV-1 and HBV who discontinue Odefsey should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, initiation of antihepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since post treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

Skin and Hypersensitivity Reactions

Severe skin and hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with RPV-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunction, including elevations in hepatic serum biochemistries. During Phase 3 clinical trials of RPV, treatment-related rashes with at least Grade 2 severity were reported in 1% of subjects. Overall, most rashes were Grade 1 or 2 and occurred in the first four to six weeks of therapy [see Adverse Reactions (6.2)].

Discontinue Odefsey immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia. Clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated.

Loss of Virologic Response Due to Drug Interactions

The concomitant use of Odefsey and other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of Odefsey and possible development of resistance due to reduced exposure of RPV.

See Table 3 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations [see Contraindications (4) and Drug Interactions (7)]. Consider the potential for drug interactions prior to and during Odefsey therapy; review concomitant medications during Odefsey therapy; and monitor for the adverse reactions associated with the concomitant drugs.

Prolongation of QTc Interval with Higher Than Recommended Dosages

In healthy subjects, higher than recommended doses of RPV (75 mg once daily and 300 mg once daily – 3 and 12 times the recommended dosages, respectively) have been shown to prolong the QTc interval of the electrocardiogram [see Drug Interactions (7.2) and Clinical Pharmacology (12.2)]. Consider alternatives to Odefsey when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsades de Pointes.

Depressive Disorders

Depressive disorders (including depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) have been reported with RPV. Promptly evaluate patients with severe depressive symptoms to assess whether the symptoms are related to Odefsey, and to determine whether the risks of continued therapy outweigh the benefits.

In Phase 3 trials of RPV in adult subjects (N=1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among RPV-treated subjects (n=686) was 9%. Most events were mild or moderate in severity. In RPV-treated subjects, the incidence of Grades 3 and 4 depressive disorders (regardless of causality) was 1%, the incidence of discontinuation due to depressive disorders was 1%, and suicidal ideation and suicide attempt was reported in 4 and 2 subjects, respectively.

During the Phase 2 trial in RPV-treated pediatric subjects 12 to less than 18 years of age (N=36), the incidence of depressive disorders (regardless of causality, severity) was 19% (7/36) through 48 weeks. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 6% (2/36). None of the subjects discontinued due to depressive disorders. Suicidal ideation and suicide attempt were reported in 1 subject.

Hepatotoxicity

Hepatic adverse events have been reported in patients receiving an RPV-containing regimen. Patients with underlying hepatitis B or C, or marked elevations in liver-associated tests prior to treatment, may be at increased risk for worsening or development of liver-associated test elevations with use of Odefsey. A few cases of hepatic toxicity have been reported in adult patients receiving a RPV-containing regimen who had no preexisting hepatic disease or other identifiable risk factors. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with Odefsey is recommended in patients with underlying hepatic disease such as hepatitis B or C, or in patients with marked elevations in liver-associated tests prior to treatment initiation. Liver-associated test monitoring should also be considered for patients without preexisting hepatic dysfunction or other risk factors.

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including FTC and RPV, both components of Odefsey. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment.

New Onset or Worsening Renal Impairment

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir prodrugs in both animal toxicology studies and human trials. In clinical trials of FTC+TAF with EVG+COBI, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). In clinical trials of FTC+TAF with EVG+COBI in treatment-naïve subjects and in virologically-suppressed subjects switched to FTC+TAF with EVG+COBI with eGFRs 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 study of virologically-suppressed subjects with baseline eGFRs between 30 and 69 mL per minute treated with FTC+TAF with EVG+COBI for a median duration of 43 weeks, FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) subjects with a baseline eGFR between 30 and 50 mL per minute [see Adverse Reactions (6.1)]. Odefsey is not recommended in patients with estimated creatinine clearance below 30 mL per minute because data in this population are insufficient.

Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents, including nonsteroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.

It is recommended that serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose and urine protein be assessed before initiating Odefsey therapy and during therapy in all patients as clinically appropriate. Discontinue Odefsey in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of Odefsey, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals. Treatment with Odefsey should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Clinical Trial Results in HIV-1 Virologically-Suppressed Subjects Who Switched to Odefsey

In Trial 1216, the efficacy and safety of switching from emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) to Odefsey were evaluated in a randomized, double-blind study of virologically-suppressed HIV-1 infected adults. Subjects were suppressed (HIV-1 RNA <50 copies/mL) on their baseline regimen of FTC/RPV/TDF for at least 6 months and have no documented resistance mutations to FTC, TAF, or RPV prior to study entry. Subjects were randomized in a 1:1 ratio to either switch to Odefsey (N=316) once daily or stay on FTC/RPV/TDF (N=314) once daily. Subjects had a mean age of 45 years (range: 23–72), 90% were male, 75% were White, and 19% were Black. The mean baseline CD4+ cell count was 709 cells/mm3 (range: 104–2527).

In Trial 1160, the efficacy and safety of switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) to Odefsey were evaluated in a randomized, double-blind study of virologically-suppressed HIV-1 infected adults. Subjects must have been stably suppressed (HIV-1 RNA <50 copies/mL) on their baseline regimen of EFV/FTC/TDF for at least 6 months and have no documented resistance mutations to FTC, TAF, or RPV prior to study entry. Subjects were randomized in a 1:1 ratio to either switch to Odefsey (N=438) once daily or stay on EFV/FTC/TDF (N=437) once daily. Subjects had a mean age of 48 years (range: 19–76), 87% were male, 67% were White, and 27% were Black. The mean baseline CD4+ cell count was 700 cells/mm3 (range: 140–1862).

Treatment outcomes of Trials 1216 and 1160 are presented in Table 11.

Clinical Trial Results for Subjects with no Antiretroviral Treatment History for Components of Odefsey

The efficacy of RPV, FTC, and TAF in the treatment of HIV-1 infection in adults as initial therapy in those with no antiretroviral treatment history [see Indications and Usage (1)] was established in trials of:

• RPV+FTC/TDF in HIV-1 infected adults as initial therapy in those with no antiretroviral treatment history (n=550). The virologic response rate (i.e., HIV-1 RNA less than 50 copies per mL) was 77% at Week 96. The virologic response rate at 96 weeks was 83% in subjects with baseline HIV-1 RNA less than or equal to 100,000 copies per mL and 71% in subjects with baseline HIV-1 RNA greater than 100,000 copies per mL. Further, the virologic response rate at 96 weeks among subjects with baseline CD4+ cell counts less than 200 and greater than or equal to 200 cells/mm3 were 68% and 82%, respectively.
• FTC+TAF with EVG+COBI in HIV-1 infected adults as initial therapy in those with no antiretroviral treatment history (n=866). The virologic response rate (i.e., HIV-1 RNA less than 50 copies per mL) was 92% at Week 48.

The efficacy of RPV, FTC, and TAF in the treatment of HIV-1 infection in pediatric patients aged 12 to less than 18 years old and greater than 32–35 kg as initial therapy in those with no antiretroviral treatment history and to replace a stable antiretroviral regimen in those who are virologically-suppressed [see Indications and Usage (1)] was established in trials of antiretroviral treatment-naïve HIV-1 infected pediatric subjects 12 to less than 18 years old with:

• RPV in combination with other antiretroviral agents in 36 treatment-naïve HIV-1 infected adolescents weighing at least 32 kg. The majority of subjects (24/36) received RPV in combination with FTC and TDF. Of these 24 subjects, 20 had a baseline HIV-1 RNA less than or equal to 100,000 copies per mL. The virologic response rate in these 20 subjects (i.e., HIV-1 RNA less than 50 copies per mL) was 80% (16/20) at 48 weeks.
• FTC+TAF with EVG+COBI in 23 adolescents weighing at least 35 kg. The virologic response rate (i.e., HIV-1 RNA less than 50 copies per mL) was 91% at 24 weeks.

In the clinical trial of 248 HIV-1 infected adult patients with estimated creatinine clearance greater than 30 mL per minute but less than 70 mL per minute, 95% (235/248) of the combined populations of treatment-naïve (N=6) begun on FTC+TAF with EVG+COBI and those previously virologically-suppressed on other regimens (N=242) and switched to FTC+TAF with EVG +COBI had HIV-RNA levels less than 50 copies per mL at Week 24.

Odefsey tablets are gray, capsule-shaped, and film coated with "GSI" debossed on one side and "255" on the other side. Each bottle contains 30 tablets (NDC 61958-2101-1), a silica gel desiccant, and a polyester coil, and is closed with a child-resistant closure.

Store below 30 °C (86 °F).

• Keep container tightly closed.
• Dispense only in original container.

Odefsey contains a combination of emtricitabine, rilpivirine, and tenofovir. Emtricitabine, rilpivirine, and tenofovir are antiviral medicines that prevent human immunodeficiency virus (HIV) from multiplying in your body. HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

Odefsey is a prescription medicine that is used to treat Human Immunodeficiency Virus-1 (HIV-1) in people who have never taken HIV medicines before. This medicine is not a cure for HIV or AIDS.

Odefsey is for use in adults and children who are at least 12 years old.

Odefsey should not be taken together with other antiviral medications to treat HIV or AIDS.

Taking Odefsey will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

If you also take an antacid, take it at least 2 hours before or 4 hours after taking Odefsey. If you also take a heartburn or GERD medicine (such as Tagamet, Pepcid, Zantac), take it at least 12 hours before or 4 hours after taking Odefsey.