Intelence

Intelence, 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 2 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.

Intelence can cause serious side effects including:

Severe skin rash and allergic reactions. Skin rash is a common side effect of Intelence. Rash can be serious. Call your doctor right away if you get a rash. In some cases, severe rash and allergic reaction may need to be treated in a hospital and may potentially lead to death. If you get a rash with any of the following symptoms, stop taking Intelence and call your doctor or get medical help right away:

• hives or sores in your mouth, or your skin blisters and peels
• trouble swallowing or breathing
• swelling of your face, eyes, lips, tongue, or throat
• fever,
• yellowing of the skin or whites of the eyes,
• dark urine, or
• pain on the right side of the stomach-area (abdominal pain).

Changes in body fat can happen in people taking HIV medicines. These changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these problems are not known.

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. Call your doctor right away if you start having any new symptoms after starting your HIV medicine. In adults, common side effects of Intelence include:

• tingling,
• numbness, or
• pain in the hands or feet.

In children, diarrhea is a common side effect of Intelence.

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects with Intelence. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Adult Patients

The recommended oral dose of Intelence tablets is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. The type of food does not affect the exposure to etravirine.

Pediatric Patients (2 Years to Less Than 18 Years of Age)

The recommended dose of Intelence for pediatric patients 2 years to less than 18 years of age and weighing at least 10 kg is based on body weight not exceeding the recommended adult dose. Intelence tablet(s) should be taken orally, following a meal. The type of food does not affect the exposure to etravirine.

Etravirine is a substrate of CYP3A, CYP2C9, and CYP2C19. Therefore, co-administration of Intelence with drugs that induce or inhibit CYP3A, CYP2C9, and CYP2C19 may alter the 9 therapeutic effect or adverse reaction profile of Intelence. Etravirine is an inducer of CYP3A and inhibitor of CYP2C9, CYP2C19 and P-glycoprotein. Therefore, co-administration of drugs that are substrates of CYP3A, CYP2C9 and CYP2C19 or are transported by P-glycoprotein with Intelence may alter the therapeutic effect or adverse reaction profile of the co-administered drug(s).

The interaction between Intelence and the following drugs were evaluated in clinical studies and no dose adjustment is needed for either drug:

• didanosine,
• enfuvirtide (ENF),
• ethinylestradiol/norethindrone,
• omeprazole,
• paroxetine,
• raltegravir,
• ranitidine, and
• tenofovir disoproxil fumarate.

Pregnancy

Pregnancy Category B No adequate and well-controlled studies of Intelence use in pregnant women have been conducted. In addition, no pharmacokinetic studies have been conducted in pregnant patients. Intelence should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Antiretroviral Pregnancy Registry To monitor maternal-fetal outcomes of pregnant women exposed to Intelence, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

Animal Data Reproductive and developmental toxicity studies were performed in rabbits (at oral doses up to 375 mg per kg per day) and rats (at oral doses up to 1000 mg per kg per day). In both species, no treatment-related embryo-fetal effects including malformations were observed. In addition, no treatment-related effects were observed in a separate pre- and postnatal study performed in rats at oral doses up to 500 mg per kg per day. The systemic drug exposures achieved in these animal studies were equivalent to those at the recommended human dose (400 mg per day).

Breastfeeding

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. It is not known whether etravirine is secreted in human milk. Because of both the potential for HIV transmission and the potential for adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Intelence.

Intelence (etravirine) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1). Etravirine is a white to slightly yellowish-brown powder. Etravirine is practically insoluble in water over a wide pH range. It is very slightly soluble in propylene glycol and slightly soluble in ethanol. Etravirine is soluble in polyethylene glycol (PEG)400 and freely soluble in some organic solvents (e.g., N,N-dimethylformamide and tetrahydrofuran).

Intelence 25 mg tablets are available as white to off-white, oval scored tablets for oral administration. Each 25 mg tablet contains 25 mg of etravirine and the inactive ingredients hypromellose, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and lactose monohydrate. Intelence 100 mg tablets are available as white to off-white, oval tablets for oral administration.

Each 100 mg tablet contains 100 mg of etravirine and the inactive ingredients hypromellose, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and lactose monohydrate. Intelence 200 mg tablets are available as white to off-white, biconvex, oblong tablets for oral administration.

Each 200 mg tablet contains 200 mg of etravirine and the inactive ingredients hypromellose, silicified microcrystalline cellulose, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium and magnesium stearate.

Mechanism of Action

Etravirine is an NNRTI of human immunodeficiency virus type 1 (HIV-1). Etravirine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. Etravirine does not inhibit the human DNA polymerases α, β, and γ.