Intelence

Contraindications

Coadministration with drugs (eg, CYP inducers) where significant decreases in etravirine plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance to other NNRTIs

Cautions

Hypersensitivity

Risk of severe skin reactions, including Stevens-Johnson Syndrome, erythema multiforme, toxic epidermal necrolysis (sometimes accompanied by hepatic failure)

Hypersensitivity reactions including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have also been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction

Discontinue if severe rash develops and initiate appropriate therapy

Risk of immune reconstitution syndrome

50% decrease in absorption when administered under fasting conditions: only take with meal

Do not coadminister with other NNRTIs

Etravirine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• vomiting
• abdominal pain
• diarrhea
• headache
• increase in blood pressure
• pain, burning, numbness, or tingling in the hands or feet

Some side effects can be serious. If you experience any of these symptoms, stop taking etravirine and call your doctor immediately:

• rash
• redness, bumps, or blisters on the skin or in the mouth
• redness or swelling of the eyes
• swelling of the face
• sore throat, cough, fever, chills, or other signs of infection
• general ill feeling
• tiredness
• muscle or joint aches
• yellowing of the skin or eyes
• dark-colored urine
• pale-colored stools
• pain in the upper right part of the stomach
• loss of appetite

Etravirine 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 Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Avoid using grapefruit juice or warm (more than 104°F or 40°C) or carbonated beverages when taking this medication.

Etravirine is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body.

Etravirine is used with other medicines to treat HIV in adults and children who are at least 6 years old. HIV causes the acquired immunodeficiency syndrome (AIDS). Etravirine is not a cure for HIV or AIDS.

Etravirine may also be used for purposes not listed in this medication guide.

You should not take etravirine if you are allergic to it.

To make sure you can safely take etravirine, tell your doctor if you have any liver disease, including hepatitis B or C.

Etravirine must be taken in combination with other HIV medications. However, there are certain combinations of medicines that should not be used together with etravirine. Follow your doctor's dosing instructions very carefully.

You SHOULD NOT take etravirine together with:

• delavirdine;

• efavirenz;

• nevirapine;

• rifabutin, rifapentine, rifampin;

• rilpivirine;

• St. John's wort;

• ritonavir when given with fosamprenavir or tipranavir;

• ritonavir in doses of more than 600 milligrams twice daily; or

• seizure medications--carbamazepine, phenytoin, phenobarbital.

You MUST take etravirine together with ritonavir if you are also taking a protease inhibitor, such as atazanavir, dolutegravir, fosamprenavir, indinavir, or nelfinavir.

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

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.

In the U.S.

• Intelence

Available Dosage Forms:

• Tablet

Therapeutic Class: Antiretroviral Agent

Pharmacologic Class: Non-Nucleoside Reverse Transcriptase Inhibitor

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of etravirine is not recommended in children younger than 6 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of etravirine in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients using etravirine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Dasabuvir

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amiodarone
• Amprenavir
• Artemether
• Atazanavir
• Avanafil
• Axitinib
• Bepridil
• Bosutinib
• Carbamazepine
• Cilostazol
• Clarithromycin
• Clopidogrel
• Cobicistat
• Cyclosporine
• Daclatasvir
• Deflazacort
• Delavirdine
• Dexamethasone
• Diazepam
• Disopyramide
• Dolutegravir
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Efavirenz
• Elbasvir
• Enzalutamide
• Etonogestrel
• Flecainide
• Fosamprenavir
• Fosphenytoin
• Grazoprevir
• Ifosfamide
• Indinavir
• Ketoconazole
• Lidocaine
• Lumefantrine
• Maraviroc
• Mexiletine
• Naloxegol
• Nelfinavir
• Nevirapine
• Nifedipine
• Orlistat
• Phenobarbital
• Phenytoin
• Piperaquine
• Posaconazole
• Propafenone
• Quinidine
• Rifabutin
• Rifampin
• Rifapentine
• Rilpivirine
• Ritonavir
• Simeprevir
• Sirolimus
• St John's Wort
• Tacrolimus
• Tipranavir
• Warfarin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atorvastatin
• Boceprevir
• Clobazam
• Digoxin
• Fluconazole
• Methadone
• Ospemifene
• Raltegravir
• Sildenafil
• Voriconazole

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Liver disease (including hepatitis B or C)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

It is important to take this medicine together with other medicines for HIV. Be sure to take all of the medicines your doctor ordered, and to take them at the right times. If you need help in planning the best times to take your medicine, check with your doctor.

It is best to take etravirine following a meal.

Swallow the tablet whole with a liquid such as water. Do not chew it. If you or your child cannot swallow the tablet whole, you may dissolve it in a glass with a small amount of water. You may also add more water, orange juice, or milk to make it easier to take. Do not use grapefruit juice, or warm or carbonated drinks. Be sure to drink or swallow the entire mixture right away. Then refill your glass with water, orange juice, or milk and drink it so that none of the medicine is left in the glass. .

Keep taking etravirine for the full time of treatment, even if you or your child begin to feel better. Do not change the amount or stop taking this medicine without checking first with your doctor. .

This medicine works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. .

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

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 HIV infection:
    • Adults—200 milligrams (mg) two times a day.
    • Children 6 years of age and older weighing at least 16 kg—Dose is based on body weight and must be determined by your doctor. The dose is usually 100 to 200 mg two times a day.
    • Children younger than 6 years of age—Use is not recommended.

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.

Do not take this medicine if it has been more than 6 hours since you missed your last dose.

Storage

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

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.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Intelence®1, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced patients ages 6 years and older, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.

The indication for adult use is based on Week 48 analyses from 2 randomized, double-blind, placebo-controlled trials of Intelence®. Both studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, N[t]RTI, PI) treatment-experienced adults. The indication for pediatric use is based on 24-week analyses of a single-arm, Phase 2 trial in antiretroviral treatment-experienced pediatric subjects 6 years to less than 18 years of age [see Use in Specific Populations (8.4)].

In treatment-experienced adult and pediatric patients, the following points should be considered when initiating therapy with Intelence®:

• Treatment history and resistance testing should guide the use of Intelence® due to concerns for potential cross-resistance [see Microbiology (12.4) and Clinical Studies (14)].
• In patients who have experienced virologic failure on an NNRTI-containing regimen, do not use Intelence® in combination with only N[t]RTIs [see Clinical Studies (14)].
• The use of other active antiretroviral agents with Intelence® is associated with an increased likelihood of treatment response.
• The safety and efficacy of Intelence® have not been established in pediatric patients less than 6 years of age or in treatment-naïve adult or pediatric patients.

Intelence (etravirine) is an antiviral medicine that prevents the human immunodeficiency virus (HIV) from multiplying in your body.

Intelence is used with other medicines to treat HIV in adults and children who are at least 6 years old. HIV causes the acquired immunodeficiency syndrome (AIDS).

Intelence is not a cure for HIV or AIDS.

Taking this medication 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.

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

In rare cases, Intelence can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.

Stop using Intelence and call your doctor at once if you have:

• swelling, rapid weight gain, little or no urinating;

• confusion, seizure;

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

• the first sign of any type of skin rash, no matter how mild; or

• severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Intelence 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 with this medicine. Tell your doctor if you have:

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

• chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

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

• rapid heart rate, 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 Intelence side effects may include:

• diarrhea;

• numbness or tingly feeling in your hands or feet;

• rash; 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.

Some drugs can raise or lower your blood levels of Intelence, which may cause side effects or make etravirine less effective. This medicine can also affect blood levels of certain other drugs, making them less effective or increasing side effects.

Many drugs can interact with etravirine. Not all possible interactions are listed here. TELL YOUR DOCTOR ABOUT ALL OTHER MEDICINES YOU USE, and any you start or stop using during treatment with Intelence, especially:

• artemether and lumefantrine;

• boceprevir or telaprevir;

• clarithromycin;

• clopidogrel;

• dexamethasone;

• diazepam (Valium);

• maraviroc;

• an antifungal medicine - itraconazole, ketoconazole, posaconazole;

• a blood thinner - warfarin, Coumadin;

• cholesterol lowering medicine - atorvastatin, fluvastatin, lovastatin, pitavastatin, simvastatin;

• heart rhythm medicine - amiodarone, digoxin, disopyramide, flecainide, mexiletine, propafenone, quinidine;

• medicine for erectile dysfunction or pulmonary arterial hypertension - sildenafil, tadalafil, vardenafil;

• medicines to prevent organ transplant rejection - cyclosporine, sirolimus, tacrolimus; or

• narcotic medication - buprenorphine, methadone.

This list is not complete. Other drugs may interact with etravirine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.