FDA Approvals & News New Boxed Warning for Elidel and ProtopicPimecrolimus (Elidel) and tacrolimus (Protopic) will soon carry a boxed warning to indicate that a possible risk of cancer exists, now that the FDA has approved new labeling.The boxed warning informs healthcare providers that the long-term safety of Elidel and Protopic has not been established. In addition, the new labeling indicates that these drugs are intended for short-term use, and if longer-term use is needed patients should take time off from these therapies first. FDA also stipulated that these drugs be accompanied by a medication guide to ensure that patients using these prescriptions medicines are aware of this concern. The labeling emphasizes that Elidel and Protopic are to be used as second-line agents, and gives patients clear indications for when and when not to use these therapies.Even though the drugs will be accompanied by a “boxed warning” but not a “black box warning”, which was initially recommended last winter by the FDA’s Pediatric Advisory Committee, there is still concern among patients regarding these therapies. “I do not understand the FDA’s efforts in this area which have resulted in high levels of fear and anxiety,” comments Steven Feldman, M.D., Ph.D., from Wake Forest University Medical Center and Chief Medical Editor for Skin & Aging. “These drugs seem like extraordinarily safe drugs. The state of terror the FDA caused in some people’s minds concerning these products seems to me to have been counterproductive to good patient care,” he adds. In a statement issued by Novartis, the manufacturer of Elidel, the company notes that “FDA’s review of the safety of topical calcineurin inhibitors was based on a theoretical risk stemming from the adverse events associated with the systemic use of calcineurin inhibitors in animal studies and transplant patients. These adverse events are associated with intense and prolonged systemic immunosuppression. This effect cannot be achieved with the topical application of Elidel Cream in patients with eczema. The absorption of Elidel Cream through the skin is so low that in most cases studied it was not possible to measure the amount of the active ingredient entering the bloodstream.”Astellas Pharma, the manufacturer of Protopic, also issued a statement that reads, “Regarding the clinical data, it’s important to note that clinical studies involving more than 19,000 patients and post-marketing data on approximately 1.7 million U.S. patients treated with Protopic do not demonstrate an increased risk of malignancy compared with the expected rates in the general population.”Both companies indicate that they are working in conjunction with FDA to communicate the labeling changes to physicians and patients. It was last February that the FDA’s Pediatric Advisory Committee took the dermatology profession by surprise when the committee recommended a black box warning, an action taken based on rare reports of cancers (skin and lymphoma, for example). Then, a month later, the FDA issued a public health advisory about the possible cancer risk.  New Indication for ThermaCoolThermage has received regulatory clearance from the FDA for a new indication for ThermaCool, its radiofrequency device. The device is now cleared for off-the-face procedures for the non-invasive treatment of rhytids. This monopolar radiofrequency device has been previously cleared for treating the periorbital region and the mid and lower face.Thermage is developing treatment protocols for off-the-face areas such as the thighs, buttocks, hands and abdomen (see photo above for results of treatment of the abdominal area in one patient). Skin & Aging NewsPast and present officers of the American Academy of Dermatology had a chance to meet Joe Torre, Manager of the New York Yankees, at the Winter Clinical Dermatology Conference — Hawaii 2006 in January. Pictured from left to right are Raymond L. Cornelison, Jr., M.D., Stephen P. Stone, M.D., Diane R. Baker, M.D., Darrell S. Rigel, M.D., Joe Torre, Clay J. Cockerell, M.D., Roger Ceilley, M.D., and Boni E. Elewski, M.D.  ClarificationThe January article “Exploring Aesthetic Interventions”, explored intense pulsed light (IPL) for treatment of numerous conditions. On page 56, the authors offered a table of IPL systems, noting parameters of each. Lumenis’s IPL systems were inadvertently omitted from the chart. The specifics of their IPL systems are noted below.Plea to Postpone iPLEDGE AADA urges the FDA to re-evaluate the isotretinoin risk management program.By Stefanie Tuleya, Managing Editor Mounting problems encountered by dermatologists with the new iPLEDGE program have prompted the American Academy of Derma-tology Association (AADA) to contact the FDA. On January 30, the AADA sent a letter to the FDA requesting that the iPLEDGE program start date of March 1 be halted and re-evaluated. Currently, the FDA is mandating that as of March 1, all prescribers, patients, pharmacies, wholesalers and manufacturers must be registered in the iPLEDGE risk management program if they want to be involved with isotretinoin (Accutane, Amnesteem, Claravis, Sotret).The letter cited the AADA’s concerns about problems with iPLEDGE, such as the inability of prescribers and patients to access the phone and Web systems in real-time, difficulties with activating prescriber registrations, illogical requirements for males and females who cannot get pregnant to fill prescriptions within 7 days of office visits, lack of availability of program materials and much more. “In short, the iPLEDGE program should not become effective on March 1 or at any time in the future unless the concerns described in this letter are fully resolved. Forcing this flawed program onto the public would not promote the health, safety, and welfare of isotretinoin patients and would be detrimental to the practice of dermatology in this country,” the letter states. (Visit www.aad.org to view the letter in its entirety.)Concern for Patient WelfareClay J. Cockerell, M.D., President of the American Academy of Dermatology, says that the letter was written in response to the many complaints AAD members were voicing about difficulty signing up for iPLEDGE. “We believe the FDA bit off much more than it can chew,” explains Dr. Cockerell. “This registry will be for 1 million prescriptions per year. The thalidomide registry, which [iPLEDGE] is basically modeled on, is for only 1,000 prescriptions per year.” He added that the FDA is being swamped with complaints from AAD members and that the Academy is concerned that some patients will not be able to continue to receive isotretinoin after March 1 for a variety of reasons and that patient care will suffer as a result.A Cumbersome ProgramDiane M. Thiboutot, M.D., Chair of the AADA’s Ad Hoc Task Force on Isotretinoin, says the iPLEDGE program goes beyond the boundaries of regulating a drug to regulating the practice of medicine.“Under previous programs, prescribers adjusted their practice patterns to comply with the regulation. Prescribers are now attempting to adjust their practice patterns to comply with iPLEDGE, but are failing because they have not been provided with the necessary details to incorporate the iPLEDGE program into their practices. Furthermore, they are failing in their attempts to get needed information and materials from the iPLEDGE call center or Web site,” says Dr. Thiboutot. Lockout ProblemsAccording to Dr. Thiboutot, one major problem with the program is that although prescribers have been asking for operational details since last August, none have been available in advance because the system is being rolled out in a “just-in-time” fashion, giving stakeholders little to no opportunity for input. Dr. Thiboutot says that most of the problems identified by AADA have not been resolved.“If the mandatory start date of March 1 is not delayed until prescribers and patients can be provided with the necessary details and materials needed to comply with this program, there will be significant drop out at all levels. This will force frustrated patients and families to purchase the medication on the Internet because they will have been unable to obtain it through their physicians, whose attempts to work within the system have failed due to the mandatory implementation of a known operationally flawed system,” explains Dr. Thiboutot.  More Details NeededWith waits of more than an hour on phone lines and patients and prescribers locked out of the program’s Web site, it has been nearly impossible for patients to fill prescriptions in the program’s mandatory 7-day window. Patients have to make repeated visits to their doctors to try to receive their medication by defaulting to the “yellow-sticker” program in place. According to the letter, the alternative to this would be to remain in iPLEDGE and go without medication for another 23 days due to a lockout resulting from the inability of the system to provide essential materials (passwords) in a timely fashion. “We have urged the FDA, Covance and the pharmaceutical manufacturers, that in the interest of patient safety and in the interest of any potential future success of this program, to delay the mandatory start date of Mar. 1, 2006, for 2 months,” says Dr. Thiboutot, “in order to provide prescribers and patients the details and materials needed to adjust their practices to comply with this program and to correct the illogical burden of a 23-day lockout . . . .”At press time, the FDA could not be reached for comment.