FDA, Roche to Implement New Dispensing Procedures for Isotretinoin
Despite extensive warnings, pregnant women continue to receive isotretinoin prescriptions, and female patients become pregnant while taking the teratogen, according to FDA.
Isotretinoin, used in the treatment of severe recalcitrant nodular acne, and widely known by the brand name Accutane, is known to cause severe birth defects and spontaneous abortion.
Starting April 10, 2002, pharmacists will be expected to dispense isotretinoin only when presented with a prescription that bears a yellow self-adhesive "Accutane Qualification Sticker" that has been completed and correctly filled in by the prescriber, according to the requirements of a new risk-management program approved by FDA.
After the program’s start date, pharmacists can dispense a 30-day supply of the medication but no refills. A new prescription with the yellow sticker must be presented each time a patient seeks an additional supply.
In addition, prescriptions intended for use by female patients should not be filled more than seven days past the qualification date.
The yellow sticker, said Thomas McGinnis, FDA’s pharmacy affairs director, is an assurance to pharmacists that a prescriber has qualified the patient to receive the drug.
Dermatologic and Ophthalmic Drugs Advisory Committee met in September 2000 to discuss the additional measures that might help prevent the exposure of unborn babies to isotretinoin.
To address the issues discussed at this meeting, F. Hoffmann–La Roche Ltd., Accutane’s manufacturer, developed the risk management program called System to Manage Accutane Related Teratogenicity (SMART).
Roche developed SMART in consultation with FDA, which approved the program October 30.
Gail Safian, spokeswoman for Roche, said SMART does not replace Roche’s Accutane Pregnancy Prevention Program, a patient education program. "It enhances it," she said.
Under the new program, each patient must be qualified by the prescriber to receive isotretinoin. This qualification signifies that each female patient has two negative urine or serum pregnancy tests before the initial prescription for isotretinoin was written, according to FDA.
For each month of therapy, female patients must have a negative pregnancy test result before receiving their next 30-day prescription. They must also commit to use two forms of contraception simultaneously, unless, according to FDA, absolute abstinence is the chosen method or the patient has undergone a hysterectomy.
Contraception use must begin at least one month before initiation of isotretinoin therapy and continue during therapy and for one month after discontinuation.
Under the qualification requirements, female patients must sign a patient information-and-consent form describing isotretinoin and birth defects. Prescribers are required to discuss with all patients other serious risks and adverse effects related to isotretinoin and obtain a signed consent form about those risks before prescribing the drug.
Prescriptions for male patients must also bear the yellow sticker to ensure that every patient has been informed and understands the risks involved.
Isotretinoin may cause depression, psychosis, and other metal disorders, according to the product’s labeling. The drug is also known to cause liver and gastrointestinal problems, in addition to hearing and vision impairments.
Roche and FDA are urging physicians to participate in a continuing-education program, available on CD-ROM, about isotretinoin.
"It's not a requirement, but we suggest they take the course," Safian said.
Under the new program, prescribers must give female patients the opportunity to enroll in the Accutane Survey.
This confidential survey, according to FDA, is a large epidemiological study of women who have taken isotretinoin and is conducted independently by the Slone Epidemiology Unit at Boston University’s School of Public Health.
Data from the survey will be reported to FDA and used to assess the effectiveness of the new program.
"It's a way for us to gauge if the program is working or not," McGinnis said.
McGinnis said pharmacists should also encourage female patients to enroll in the survey.
"We want pharmacists to be actively involved in the SMART program," he said.
Pharmacists are required by law to dispense to every patient the medication guide with every Accutane prescription, according to FDA.
On January 2, 2002, Roche will conduct a mass mailing to 10,000 dermatologists, 300,000 primary care physicians, and 65,000 pharmacies that will include the SMART Guide to Best Practices, an information booklet containing guidelines and information for physicians, pharmacists, and patients, Safian said.
Physicians also will receive the Accutane Letter of Understanding that they must sign and return to Roche before they can receive the yellow stickers.
The mailing to pharmacists will include a letter with specific guidelines for dispensing the medication.
As of April 10, pharmacists are prohibited to fill electronic prescriptions for isotretinoin or prescriptions sent over the phone or fax for the drug.
McGinnis said he has had discussions with the pharmacy community, including the American Society of Health-System Pharmacists, about the possible development and approval in the future of an electronic yellow sticker.
But, McGinnis said, after the April 10 start date of the new program, it will be "illegal" for pharmacists to fill a prescription without the paper script and the yellow sticker attached.
Safian said Roche will conduct an audit of pharmacies to check for the yellow sticker on prescriptions for isotretinoin.
McGinnis said it would be up to individual state boards of pharmacy to enforce the requirement.
Safian said mail-order pharmacies could fill isotretinoin prescriptions after April 10. But, she said, those pharmacies have to stick to the 7-day rule for female patients and the 30-day supply rule for all