Intelence Information
Intelence (Etravirine) Indications And Usage
Intelence (Etravirine) , in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.
This indication is based on Week 48 analyses from 2 randomized, double-blind, placebo-controlled trials of Intelence (Etravirine) . Both studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, N[t]RTI, PI) treatment-experienced adults.
The following points should be considered when initiating therapy with Intelence (Etravirine) :
Intelence (Etravirine) Dosage And Administration
The recommended oral dose of Intelence (Etravirine) 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. Patients who are unable to swallow Intelence (Etravirine) tablet(s) whole may disperse the tablet(s) in a glass of water. Once dispersed, patients should stir the dispersion well and drink it immediately. The glass should be rinsed with water several times and each rinse completely swallowed to ensure the entire dose is consumed.
Intelence (Etravirine) Contraindications
Intelence (Etravirine) Warnings And Precautions
Severe, potentially life-threatening, and fatal skin reactions have been reported. These include cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme. Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. In Phase 3 clinical trials, Grade 3 and 4 rashes were reported in 1.3% of subjects receiving Intelence (Etravirine) compared to 0.2% of placebo subjects. A total of 2.2% of HIV-1-infected subjects receiving Intelence (Etravirine) discontinued from Phase 3 trials due to rash []. Rash occurred most commonly during the first 6 weeks of therapy.
Discontinue Intelence (Etravirine) immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema). Clinical status including liver transaminases should be monitored and appropriate therapy initiated. Delay in stopping Intelence (Etravirine) treatment after the onset of severe rash may result in a life-threatening reaction.
Intelence (Etravirine) Adverse Reactions
The following adverse reactions are described in greater detail in other sections:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety assessment is based on all data from 1203 subjects in the Phase 3 placebo-controlled trials, TMC125-C206 and TMC125-C216, conducted in antiretroviral treatment-experienced HIV-1-infected adult subjects, 599 of whom received Intelence (Etravirine) (200 mg b.i.d.). In these pooled trials, the median exposure for subjects in the Intelence (Etravirine) arm and placebo arm was 52.3 and 51.0 weeks, respectively. Discontinuations due to adverse drug reactions (ADRs) were 5.2% in the Intelence (Etravirine) arm and 2.6% in the placebo arm.
The most frequently reported ADR at least Grade 2 in severity was rash (10.0%). Stevens-Johnson syndrome, drug hypersensitivity reaction and erythema multiforme were reported in
The following events have been identified during postmarketing use of Intelence (Etravirine) . Because these events are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Musculoskeletal and Connective Tissue Disorders
Intelence (Etravirine) Drug Interactions
Etravirine is a substrate of CYP3A, CYP2C9, and CYP2C19. Therefore, co-administration of Intelence (Etravirine) with drugs that induce or inhibit CYP3A, CYP2C9, and CYP2C19 may alter the therapeutic effect or adverse reaction profile of Intelence (Etravirine) (see ). [.]
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 (Etravirine) may alter the therapeutic effect or adverse reaction profile of the co-administered drug(s) (see )..]
Table 3 shows the established and other potentially significant drug interactions based on which, alterations in dose or regimen of Intelence (Etravirine) and/or co-administered drug may be recommended. Drugs that are not recommended for co-administration with Intelence (Etravirine) are also included in Table 3.
In addition to the drugs included in Table 3, the interaction between Intelence (Etravirine) 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.
Intelence (Etravirine) Use In Specific Populations
The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.
mothers should be instructed not to breastfeed if they are receiving Intelence (Etravirine)
Intelence (Etravirine) Overdosage
There is no specific antidote for overdose with Intelence (Etravirine) . Human experience of overdose with Intelence (Etravirine) is limited. The highest dose studied in healthy volunteers was 400 mg once daily. Treatment of overdose with Intelence (Etravirine) consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. If indicated, elimination of unabsorbed active substance is to be achieved by emesis or gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance. Because etravirine is highly protein bound, dialysis is unlikely to result in significant removal of the active substance.
Intelence (Etravirine) Description
Intelence (Etravirine) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1).
The chemical name for etravirine is 4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethylbenzonitrile. Its molecular formula is CHBrNO and its molecular weight is 435.28. Etravirine has the following structural formula:
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 (Etravirine) 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 (Etravirine) 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.
Intelence (Etravirine) How Supplied/storage And Handling
Intelence (Etravirine) 100 mg tablets are supplied as white to off-white, oval tablets containing 100 mg of etravirine. Each tablet is debossed with "TMC125" on one side and "100" on the other side.
Intelence (Etravirine) 200 mg tablets are supplied as white to off-white, biconvex, oblong tablets containing 200 mg of etravirine. Each tablet is debossed with "T200" on one side.
Intelence (Etravirine) tablets are packaged in bottles in the following configuration:
Intelence (Etravirine) Patient Counseling Information
A statement to patients and healthcare providers is included on the product's bottle label: A Patient Package Insert for Intelence (Etravirine) is available for patient information.
Patients should be informed that Intelence (Etravirine) is not a cure for HIV infection. Patients must stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses. Patients should be advised to continue to practice safer sex and to use latex or polyurethane condoms to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions or blood. Patients should also be advised to never re-use or share needles. Patients should be told that sustained decreases in plasma HIV RNA have been associated with a reduced risk of progression to AIDS and death. Patients should remain under the care of a physician while using Intelence (Etravirine) .
Patients should be advised to take Intelence (Etravirine) following a meal twice a day as prescribed. The type of food does not affect the exposure to etravirine. Patients should be instructed to swallow the tablets as a whole with a liquid such as water. Patients who are unable to swallow the Intelence (Etravirine) tablets whole may disperse the tablets in a glass of water. Once dispersed, patients should stir the dispersion well, and drink it immediately. The glass should be rinsed with water several times, and each rinse completely swallowed to ensure the entire dose is consumed. Intelence (Etravirine) must always be used in combination with other antiretroviral drugs. Patients should not alter the dose of Intelence (Etravirine) or discontinue therapy with Intelence (Etravirine) without consulting their physician. If the patient misses a dose of Intelence (Etravirine) within 6 hours of the time it is usually taken, the patient should be told to take Intelence (Etravirine) following a meal as soon as possible, and then take the next dose of Intelence (Etravirine) at the regularly scheduled time. If a patient misses a dose of Intelence (Etravirine) by more than 6 hours of the time it is usually taken, the patient should be told not to take the missed dose and simply resume the usual dosing schedule. Inform the patient that he or she should not take more or less than the prescribed dose of Intelence (Etravirine) at any one time.
Intelence (Etravirine) may interact with many drugs; therefore, patients should be advised to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St. John's wort.
Patients should be informed that severe and potentially life-threatening rash has been reported with Intelence (Etravirine) . Rash has been reported most commonly in the first 6 weeks of therapy. Patients should be advised to immediately contact their healthcare provider if they develop rash. Instruct patients to immediately stop taking Intelence (Etravirine) and seek medical attention if they develop a rash associated with any of the following symptoms as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome, toxic epidermal necrolysis or severe hypersensitivity: fever, generally ill feeling, extreme tiredness, muscle or joint aches, blisters, oral lesions, eye inflammation, facial swelling, swelling of the eyes, lips, mouth, breathing difficulty, and/or signs and symptoms of liver problems (e.g., yellowing of your skin or whites of your eyes, dark or tea colored urine, pale colored stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching or sensitivity on your right side below your ribs). Patients should understand that if severe rash occurs, they will be closely monitored, laboratory tests will be ordered and appropriate therapy will be initiated.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy, including Intelence (Etravirine) , and that the cause and long-term health effects of these conditions are not known at this time.
Intelence (Etravirine)
Intelence (Etravirine)
Intelence (Etravirine)
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