Prescribing Isotretinoin:
The Search for a Workable
Risk Management Program

D uring the summer meeting of the American Academy of Dermatology last month, dermatologists were eager to view and discuss the final guidelines for the new isotretinoin risk management program, iPledge. But the meeting never took place, leaving a lot of questions unanswered and concern that the iPledge pregnancy risk management program may get implemented without important changes that the Academy insists need to be made. “The reason the meeting was canceled is that the iPledge material has not been finalized,” explained Barbara Reed, M.D., Chair of the Ad Hoc Task Force on Isotretinoin. “It would have been confusing to present partial information,” she added. There is a sense of urgency regarding the specifics of the proposed iPledge system. At this point, the FDA has not approved iPledge, but could do so any day. And in the view of the AAD, if iPledge does not incorporate the important changes it recommended, then there is concern that the program will not be workable for patients or prescribers, and concern for patient safety. Moreover, there’s an overall concern about whether iPledge will be unsuccessful, which it is feared could potentially lead to the removal of isotretinoin from the market. iPledge vs. S.M.A.R.T. The current isotretinoin pregnancy risk management program, known as the System to Manage Accutane Related Teratogenicity (S.M.A.R.T.), was launched in 2002. “When S.M.A.R.T. was launched,” explained Dr. Reed, “we had excellent communications with Roche and the FDA, and this program rolled out with relatively few problems.” However, in February 2004 the FDA reviewed 2 years of data on S.M.A.R.T. and the companion programs required of all isotretinoin manufacturers to determine effectiveness. It was found that roughly the same number of pregnancies in patients taking isotretinoin occurred before S.M.A.R.T. as after the program was implemented. At that point, the FDA got together with all of the drug companies that manufacture isotretinoin. The consensus of the drug companies was to develop a mandatory registry, an approach the FDA approved on the basis of a positive recommendation from an FDA advisory committee meeting held in February 2004. Based on current knowledge, it is expected that iPledge will replace S.M.A.R.T. when it is launched Nov. 1, 2005. Compared to the launch of S.M.A.R.T., the launch of iPledge is creating a lot of uncertainty and concern. “Dermatologists are the major prescribers of isotretinoin,” said Dr. Reed. “We account for about 85% to 90% of all of the prescriptions written for isotretinoin.” Yet, Dr. Reed said she was confused by the lack of contact the drug companies have made to the dermatology community in developing iPledge. “We’re not sure what has kept this communication from happening, but we are hopeful that the drug companies and FDA will heed our concerns since we are the physicians who will most often prescribe this drug and know what can help iPledge to be a success.” AAD Recommendations for Improving iPledge On June 30, the AAD sent the following recommended changes to iPledge to Lester Crawford, then Acting Commissioner of the FDA, as well as to the isotretinoin manufacturers and Covance, the vendor selected by the drug companies to design and operate the new program. The changes to the iPledge program requested by the AAD are based on recommendations by a work group comprised of isotretinoin experts drawn from the Academy’s membership, representatives of acne patient advocates and dermatology physician assistants. The following points were identified as high-priority changes: • The requirement to include a written prescription should be eliminated from iPledge. Instead, the AAD would like to see the option of phone, faxing or e-mailing a prescription to the pharmacy. The AAD work group pointed out that with a mandatory registry there’s not a need for the yellow sticker that signifies that the patient received a negative pregnancy test. The patient is tracked by computer in the mandatory registry and will not receive a prescription from the pharmacist unless a negative pregnancy test result is keyed into the registry. If practitioners can phone, fax or e-mail the patient’s prescription to the pharmacy, then it will eliminate the need for the patient to have to return to the dermatologist’s office for the yellow sticker, thereby eliminating potential hardship to patients who have difficulties returning to the office. • Within the prescribing program guidelines, the term “office visit” needs to be defined. The 7-day window in which prescriptions must be filled must be better defined. Instead of the 7-day period beginning at the date of the office visit and before the pregnancy test results have been received, the Academy recommends that day 1 of the 7-day window begin the day the pregnancy test result is received when the patient can move forward with attaining the prescription. • Prescriber duties and which of those duties can be delegated to other office staff needs re-examination. If dermatologists are required to register patients, enter pregnancy results, etc., then they will have far less time to spend with patients. The AAD is requesting that tasks such as these be allowed to be delegated to other office personnel under supervision by the physician. • Consent forms must be provided, reviewed and allowed to be modified if necessary. An essential part of iPledge, these forms have not been provided to the Academy for review. The AAD has concerns about this because of the 30-day post-treatment requirements for females of childbearing potential. The Academy wants to ensure that language is included on the form that would indicate that a female patient is responsible for taking two forms of contraception and for getting a pregnancy test 30 days after taking her last pill. This language would establish a legal “hold harmless” for practitioners of patients who don’t comply. • Other concerns about the new program include clearing up confusing language now included in the iPledge materials, eliminating unnecessary medical jargon and symbols in patient pamphlets, and developing a clear-cut plan of what steps to take if a patient’s prescription is denied. In addition, the AAD recommends that iPledge undergo pilot testing before its final implementation. Next Step At this point, the FDA could approve iPledge any day. Nationwide, dermatologists are contacting the FDA Commissioner to urge him not to approve iPledge until the dermatology recommended improvements are included. The race is on to persuade the FDA and the manufacturers of isotretinoin to make changes to the program that reflect what dermatologists see as essential to making iPledge a workable plan, boosting its chances for success. “Our goal,” said Dr. Reed, “is to improve iPledge before the program is launched, not after.”