An Overview of Complera (Rilpivirine/Tenofovir/Emtricitabine)

Brand Name: Complera
Drug Class: Combination Drugs

Emtricitabine/rilpivirine/tenofovir DF, also known as FTC/RPV/TDF or Complera, is a fixed-dose combination (FDC) tablet containing three antiretroviral medicines. Rilpivirine (Edurant) is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Emtricitabine (Emtriva) and tenofovir DF (Viread) are nucleoside reverse transcriptase inhibitors (NRTIs).

Complera works by disrupting one of the early steps in the HIV life cycle, called reverse transcription. During normal reverse transcription, HIV's reverse transcriptase enzyme (a type of protein) converts HIV's RNA -- a single strand of genetic information -- into DNA -- a double strand of genetic information. It does this by recoding the RNA building blocks into complementary DNA building blocks. As the HIV life cycle proceeds, the newly formed DNA is used to make more copies of HIV virus.

When Complera is present, however, rilpivirine, one of the active ingredients, attaches directly to reverse transcriptase, blocking the conversion of RNA into DNA. Emtricitabine and tenofovir DF, the other two active drug ingredients of Complera, competes with available DNA building blocks called deoxycytidine 5'-triphosphate and deoxyadenosine 5′-triphosphate. By replacing these DNA building blocks in the newly developing HIV DNA, emtricitabine and tenofovir DF are able to stop reverse transcriptase from completing its job. This prevents the HIV DNA strand from being formed. The processes of rilpivirine, emtricitabine, and tenofovir DF halt the HIV life cycle.

HIV/AIDS-Related Uses

Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera) was approved by the U.S. Food and Drug Administration (FDA) on August 10, 2011 for treatment of HIV-1 infection in antiretroviral treatment-naive adult patients (patients who have never taken HIV therapies, and are starting HIV therapy for the first time). Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination tablet is a complete regimen for treatment of HIV infection in treatment-naive patients; therefore, Complera should not be administered with other antiretroviral medications.

Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination does not cure or prevent HIV infection or AIDS and does not reduce the risk of passing the virus to other people.

Dosage Form/Administration

Always take this medication as your doctor instructs. Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination tablets (Complera) are taken by mouth with food (a meal).

Dosage forms and strengths

• Tablet (fixed-dose combination): emtricitabine 200 mg/rilpivirine 25 mg/tenofovir DF 300 mg

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

What other information should I know?

• Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
• It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Other drugs that contain emtricitabine, rilpivirine, or tenofovir DF

• Efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla)
• Emtricitabine (Emtriva)
• Tenofovir DF/emtricitabine (Truvada)
• Tenofovir DF (Viread)
• Rilpivirine (Edurant)

What storage conditions are needed for this medication?

Store emtricitabine/rilpivirine/tenofovir DF fixed-dose combination tablets (Complera) at room temperature between 59°F to 86°F (15°C to 30°C).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

Recommended Daily Dose

For the treatment of HIV-1 infection in antiretroviral treatment-naive adult patients:

• One tablet (FTC 200 mg/RPV 25 mg/TDF 300 mg) taken once daily by mouth and with a meal

Note:

• Depending on certain factors, emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera) may not be right for you. Always take emtricitabine/rilpivirine/tenofovir DF fixed-dose combination tablets exactly as prescribed by your doctor.
• Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination tablet (Complera) is NOT recommended for use in patients less than 18 years of age.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed dose.

Contraindications

What special precautions should I follow?

Before taking emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera),

• Tell your doctor and pharmacist if you are allergic to emtricitabine, rilpivirine, tenofovir DF or any other medications.
• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
• Tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking emtricitabine/rilpivirine/tenofovir DF fixed-dose combination, call your doctor.
• Tell your doctor if you are breast-feeding. You should not breastfeed if you are infected with HIV or if you are taking emtricitabine/rilpivirine/tenofovir DF fixed-dose combination.
• Note that many different medicines should not be used if you are taking emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera). Ask your doctor or pharmacist to find out more information about these medicines.
• Tell your doctor about any medical conditions you may have had or currently have, including liver problems (such as hepatitis B or C virus infection), kidney problems, bone problems, and mental health problems.

Possible Side Effects

Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination may cause side effects.

The following life-threatening or serious side effects have been reported. Contact your doctor immediately if you experience:

Lactic Acidosis (buildup of an acid in the blood). This can be a medical emergency and may require treatment in the hospital. Call your health care provider right away if you experience any of the following signs of lactic acidosis:

• weak or tired
• unusual muscle pain
• trouble breathing
• stomach pain with nausea and vomiting
• cold sensation, especially in your arms and legs
• dizzy or lightheaded
• fast or irregular heartbeat

Hepatoxicity (serious liver problem). Some patients may develop hepatotoxicity with hepatomegaly (liver enlargement) and steatosis (fat in the liver). Call your health care provider right away if you experience the following signs of liver problems:

• skin or white part of the eyes turn yellow (jaundice)
• urine turns dark
• bowel movements turn light in color
• uninterested in eating food for several days or longer
• nauseous
• stomach pain

Note: You may be more likely to experience lactic acidosis or liver problems if you are female, are very overweight (obese), or have been taking nucleoside analog medicines, including tenofovir DF, an active ingredient of Complera, for a long time.

Flare-ups of Hepatitis B Virus (HBV) Infection. In patients coinfected with HBV, an HBV flare-up can occur upon stopping emtricitabine or tenofovir DF. A flare-up is when the disease suddenly returns in a worse way than before. Tell your health care provider about any new or unusual symptoms you may have after you stop taking emtricitabine or tenofovir DF.

New Onset or Worsening Renal (Kidney) Impairment. Kidney problems, including kidney failure, can occur in patients taking tenofovir DF, an active ingredient in Complera. Patients who have had kidney problems in the past or are taking other medicines that can cause kidney problems may require routine blood tests to check for renal impairment.

Depressive Disorder. Symptoms of depressive disorder may develop in patients taking emtricitabine/rilpivirine/tenofovir DF. Patients with severe depressive symptoms should seek immediate medical attention. Contact your doctor if you experience:

• feeling sad or hopeless
• have thoughts of hurting yourself (suicide) or have tried to hurt yourself
• unusual anxiety, restlessness, or irritability

Decreases in Bone Mineral Density. Bone problems include bone pain, softening or thinning (which may lead to fractures). Your doctor may need to do additional tests to check your bones.

Fat Redistribution (changes in body fat). Changes may include an increased amount of fat in the upper back and neck (buffalo hump), chest, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also occur. The exact cause and long-term health effects of these problems are not known.

Immune Reconstitution Syndrome (changes in your immune system). This can occur when you start HIV medicines. As your immune system becomes stronger, your body may begin to fight infections that have been "hidden" in your body for a long time. Call your doctor immediately if you start having any new symptoms after starting your HIV medicine.

Common side effects that may be associated with emtricitabine/rilpivirine/tenofovir DF fixed-dose combination include the following. Let your doctor know if any of these side effects do not go away or worsen:

• insomnia
• headache
• rash (contact your doctor if you develop a rash)
• diarrhea
• nausea
• fatigue
• dizziness
• depression
• abnormal dreams
• vomiting
• stomach pain/discomfort
• skin discoloration (small sports or freckles)
• pain

Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera) may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the U.S. FDA's MedWatch Adverse Event Reporting program online at www.fda.gov/Safety/MedWatch or by phone at 1-800-332-1088.

Drug and Food Interactions

Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera) may interact with other medicines. Before taking emtricitabine/rilpivirine/tenofovir DF fixed-dose combination, it is important to tell your doctor about any prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

The following medicines should not be used with emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera):

• anti-seizure medicines: carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• anti-tuberculosis medicines: rifabutin, rifampin, rifapentine
• proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
• dexamethasone (more than one dose)
• St. John's wort (Hypericum perforatum)
• medicines that contain lamivudine (Epivir, Epivir-HBV, Epzicom, Combivir, Trizivir)
• adefovir dipivoxil

Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination tablet (Complera) is a complete regimen for the treatment of HIV-1 infection; therefore, Complera should not be used with other antiretroviral medications for the treatment of HIV-1 infection.

Do not take emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera) with other medicines that contain the same active ingredients, such as:

• Efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla)
• Emtricitabine (Emtriva)
• Tenofovir DF/emtricitabine (Truvada)
• Tenofovir DF (Viread)
• Rilpivirine (Edurant)

Other medicines that may interact with emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera) and should be used with caution include the following:

• antacids (such as aluminium, magnesium hydroxide, or calcium carbonate)
• antifungal medicines (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole)
• H2-receptor antagonists (cimetidine, famotidine, nizatidine, ranitidine). Take these medicines at least 12 hours before or at least 4 hours after you take Complera.
• antibiotics (clarithromycin, erythromycin, troleandomycin)
• methadone

In addition to the lists above, there are other medicines that may interact with emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera). For a complete list of all medicines that may interact with emtricitabine/rilpivirine/tenofovir DF fixed-dose combination, talk with your doctor or pharmacist and check the manufacturer's website for the full prescribing information.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet. Emtricitabine/rilpivirine/tenofovir DF fixed-dose combination (Complera) should always be taken with food (a meal).

Clinical Trials

Click here to search ClinicalTrials.gov for trials that use Emtricitabine/Rilpivirine/Tenofovir disoproxil fumarate.

Manufacturer Information

Complera
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Phone: (650) 574-3000
Fax: (650) 578-9264

Emtricitabine/Rilpivirine/Tenofovir disoproxil fumarate
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Phone: (650) 574-3000
Fax: (650) 578-9264