FDA Notifications
New pediatric guidelines published by NIH, CDC
New guidelines, published by the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), are available through the AIDSinfo web site to assist health care workers in preventing and treating the secondary infections that can afflict U.S. children exposed to, or infected with, HIV.
The new guidelines, containing recommendations from the CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics, provide a reference manual for the treatment of secondary infections related to HIV, describe warning signs of potentially hazardous interactions between drugs used to treat HIV and its secondary infections, describe current standards for treating the inflammation accompanying immune system recovery made possible by new anti-HIV drugs, and provide guidance about when to discontinue preventative treatment no longer needed after the immune system has recovered.
Specifically, these pediatric guidelines include:
- Emphasis on the importance of effective antiretroviral therapy to improve children's immune function;
- Information on diagnosing and managing immune reconstitution inflammatory syndrome;
- Information on the management of antiretroviral therapy in children with opportunistic infections, including potential drug-drug interactions;
- New guidance on use of antibiotic drugs to prevent Pneumocystis jirovecii pneumonia in infants;
- Updated immunization recommendations for HIV-exposed and -infected children, including hepatitis A, human papillomavirus, meningococcal, and rotavirus vaccines;
- A new section outlining treatments for malaria, which may become an opportunistic infection in HIV-infected immigrant children or HIV-infected children who travel to countries with malaria;
- New recommendations on when to discontinue medication for preventing opportunistic infections.
Dear Healthcare letter for etravirine
Tibotec Therapeutics, in cooperation with the U.S. Food and Drug Administration, issued a Dear Healthcare Professional letter to relay important, updated prescribing information for etravirine (Intelence©) which reflects an important safety update regarding severe skin and hypersensitivity reactions.
You can view the Dear Health Professional Letter at http://www.tibotectherapeutics.com.
The text of the letter appears below: "IMPORTANT DRUG WARNING August 2009 Dear Healthcare Professional:
Tibotec Therapeutics, in cooperation with the U.S. Food and Drug Administration, would like to inform you of an important safety update to the Severe Skin Reactions WARNINGS AND PRECAUTIONS section (5.1) of the INTELENCE (etravirine) tablets prescribing information.
Specifically, the existing Warning and Precaution regarding Severe Skin Reactions has been strengthened to reflect that there have been postmarketing reports of:
- fatality due to toxic epidermal necrolysis
- hypersensitivity reactions, sometimes accompanied by hepatic failure
Additionally, Guidance has been added that INTELENCE should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop. Given the clinical relevance of these adverse reactions, the following information regarding severe skin and hypersensitivity reactions has been included in the INTELENCE Prescribing Information:
5.0 WARNINGS AND PRECAUTIONS
5.1 Severe Skin and Hypersensitivity Reactions
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™ compared to 0.2% of placebo subjects. A total of 2% of HIV-1-infected subjects receiving INTELENCE™ discontinued from Phase 3 trials due to rash [see Adverse Reactions (6)]. Rash occurred most commonly during the first 6 weeks of therapy.
Discontinue INTELENCE™ 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). Clinical status including liver transaminases should be monitored and appropriate therapy initiated. Delay in stopping INTELENCE™ treatment after the onset of severe rash may result in a life-threatening reaction.
In addition, the following sections of the INTELENCE Prescribing Information have been updated to include this new information: Highlights of Prescribing Information, Adverse Reactions and Patient Counseling. Furthermore the "What are the possible side effects of INTELENCE?" section of the patient Package Insert has also been updated.
Clinical Trials Experience:
In Phase 3 studies, the most frequently reported adverse drug reaction of at least Grade 2 in severity was rash (9.0%). Stevens-Johnson syndrome, hypersensitivity reaction, and erythema multiforme were reported in < 0.1% of subjects during clinical development with INTELENCE. In general, in clinical trials, rash was mild to moderate, occurred primarily in the second week of therapy, and was infrequent after Week 4. Rash generally resolved within 1-2 weeks on continued therapy. A total of 2% of HIV-1 infected subjects in Phase 3 trials receiving INTELENCE discontinued due to rash.
Overall, the cases referenced above within clinical and post-marketing experience illustrate the importance of clinical vigilance and familiarity with the signs and symptoms of severe skin rash and hypersensitivity reactions. Additionally they also underscore the importance of immediate discontinuation of INTELENCE in cases where severe rash or hypersensitivity reaction is suspected.
Enclosed, please find the updated Prescribing Information as well as the Patient Package Insert.
Please see INTELENCE Indication and additional Important Safety Information included on page 3 and page 4 of this letter.
Tibotec Therapeutics is committed to ensuring that INTELENCE is used safely and effectively and providing you with the most current information for our products.
Should you have any questions, require further information on product safety, or wish to report adverse patient experiences, please contact Tibotec Therapeutics Medical Information at 1-877-REACH TT (1-877-732-2488).
Alternatively, adverse events may be reported to FDA's MedWatch reporting system:
- By phone (1-800-FDA-1088), by facsimile (1-800-FDA-0178),
- Online (https://www.accessdata.fda.gov/scripts/medwatch/);
- Mailed, using the MedWatch FDA 3500 postage paid form, to the FDA Safety Information and Adverse Event Reporting Program, 5600 Fishers Lane, Rockville, MD 20852-9787.
Sincerely,
Ron Falcon, MD
Vice President, Clinical Affairs"
Generic efavirenz/emtricitabine/ fenofovir has tentative approval
On Aug. 12, 2009, the FDA granted tentative approval for a generic fixed dose combination product containing efavirenz/emtricitabine/fenofovir disoproxil fumarate 600 mg/200 mg/300 mg manufactured by Matrix Laboratories Limited of Hyberdad, India. It is indicated for use alone or in combination with other antiretroviral products for the treatment of HIV-1 infection in adults.
"Tentative approval" means that FDA has concluded that a drug product meets all required quality, safety and efficacy standards, but is not presently eligible for final approval or marketing in the U.S. because of existing patents and/or exclusivity rights. However, tentative approval does make the product eligible for purchase outside the United States under the President's Emergency Plan for AIDS Relief (PEPFAR).
As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility, and of the facilities performing the bioequivalence studies, to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application prior to granting approval or tentative approval to these applications.
The product is a generic formulation of Atripla Tablets, 600 mg/200 mg/300 mg of Gilead Sciences Inc., which is subject to various patent protections.
Patent information is available for this and other approved products in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book").
A complete list of all Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan is available on the FDA web site.
New guidelines, published by the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), are available through the AIDSinfo web site to assist health care workers in preventing and treating the secondary infections that can afflict U.S. children exposed to, or infected with, HIV.Subscribe Now for Access
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