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|Owner||Food and Drug Administration|
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The iPLEDGE program is a mandatory distribution program in the United States for isotretinoin (commonly sold under the trade names Claravis, Absorica, Amnesteem, Myorisan, Sotret or Zenatane), intended to prevent the use of the drug during pregnancy due to the high risk of birth defects (see Teratogenicity of isoretinoin). As of March 1, 2006, patients and their doctors and pharmacists are required by the U.S. Food and Drug Administration (FDA) to register and use a web site in order to receive this medication.
Overview and Process
The iPLEDGE Program website and automated phone system are part of the iPLEDGE Program, which is an FDA-mandated REMS (Risk Evaluation Mitigation Strategy) program designed to mitigate the risks associated with taking isotretinoin. The stated goal is to prevent female patients of childbearing potential from receiving the drug if they are pregnant, and to prevent them from becoming pregnant if they are taking the drug.
Once a doctor decides a patient is a candidate for isotretinoin, they will counsel the patient to ensure the patient understands the drug and the potential side effects. Once you sign the necessary paperwork, your doctor will give you a patient ID number and ID card, as well as other program educational materials. After you've been registered in iPLEDGE by your doctor, you'll receive your password in the mail after 5-10 business days. Patients are classified either as females of child-bearing potential (FCBPs), females not of child-bearing potential (FnCBPs) or males.
FCBPs are required to pick and use two birth control methods (abstinence included), and must take doctor-administered pregnancy tests in two consecutive months. After the second (confirmatory) pregnancy test, the FCBP must also take an online comprehension test to ensure they understand the requirements of the Program. Once those two items are complete, the FCBP is authorized to receive drug at an authorized pharmacy. From the date of the second (confirmatory) pregnancy test, FCBPs have 7 days to pickup their prescription. FCBPs must see their doctor and take a pregnancy test in each subsequent month in order to get another prescription for the next 30 days.
Males and FnCBPs must see their doctor every month, but don't have to take the pregnancy or comprehension tests. They have 30 days from the dates of their office visit to pickup their prescriptions - after that point they have to see their doctor for another 30-day prescription.
Before dispensing isotretinoin, the pharmacist will check the iPLEDGE Program website to ensure the patient is authorized to receive drug. Isotretinoin may only be dispensed at authorized US pharmacies that are registered with the iPLEDGE Program, and FDA has taken action against Canadian and internet pharmacies that insist upon dispensing isotretinoin outside of the iPLEDGE Program.
The typical course of isotretinoin treatment will last 4-5 months, and is generally considered the be an option when nothing else has worked.<https://www.ipledgeprogram.com/>
The iPLEDGE program was instituted by the FDA on March 1, 2006 as a replacement for the failed SMART program (System to Manage Accutane Related Teratogenicity). Instituted in April 2002, SMART aimed to eliminate isotretinoin-induced birth defects by preventing pregnant women from being prescribed or exposed to the drug. The program mandated two consecutive negative pregnancy tests, birth defect risk counseling and a pledge to use two forms of contraception when engaging in intercourse for all women of childbearing age seeking an isotretinoin prescription. A voluntary registration program called The Accutane Survey was also established. However, no effort was made to verify the compliance of doctors and pharmacists, only a small percentage of women registered in the survey, and isotretinoin's reputation as an acne wonder drug continued to fuel demand for new prescriptions, an increasing number of which were being written and dispensed for relatively minor cases of acne vulgaris without proper screening, supervision or evidence that less risky medications had first been attempted.
Failure of previous system
In 2003, a first-year review of SMART compliance conducted by the pharmaceutical industry revealed that the number of pregnant women prescribed isotretinoin actually increased by hundreds of documented cases over the previous year, before the program was instituted. Of these cases, the majority of women underwent abortions—either spontaneous or elective—with a handful of children reported to be born with typical isotretinoin-induced birth defects. When surveyed, many pregnant women reported that their physicians had attempted to downplay the risks of isotretinoin or violated the standards in other ways, such as failing to inform women they needed to use two forms of birth control or allowing them to substitute a single, less-accurate urine pregnancy test conducted in the doctor's office for the two laboratory-conducted blood pregnancy tests mandated by SMART. The FDA also concluded that, considering the voluntary nature of the reporting program and lack of mandatory record-keeping, the actual number of pregnant women affected was likely far higher than the reported number.
Introduction of mandatory reporting and verification
The report led to SMART being dismissed as "a total failure", with the FDA quickly moving to halt the downward slide with a stricter mandatory registry system to document and verify all isotretinoin prescriptions written or dispensed to childbearing-age women in the United States. This was a feature originally included in the plan for SMART recommended by the original FDA advisory panel and wholeheartedly endorsed by the pharmaceutical manufacturers, but removed due to concerns that political opposition from lobbying groups would delay the program's implementation. Although eventually resolved, the older concerns proved valid in 2003 when the launch of iPLEDGE was held up for three years while objections from women's rights, patient's rights, physician's rights and pro-choice lobbyists were debated in committee.
Criticisms of the iPLEDGE program include the following:
Difficulty of compliance
The time and expense of compliance with iPLEDGE is significant, and may pose a barrier to treatment if doctors do not wish to expend the effort required.
A physician said[who?], "It will be easier to get a firearm, an abortion or thalidomide, than to obtain this safe and important medication." He went on to say that this program requires the pharmacist, the physician, and the patient to get online, answer personal and sensitive questions about the patients' sexual practices, urine tests, and menstrual cycles to a faceless governmental confessor, all according to a very tight schedule, just so that a patient may have her acne treated. If any of the numerous requirements are not met, the drug cannot be dispensed and further activity for the patient is delayed for 30 days."
For many patients, the iPLEDGE program has caused delays in receiving isotretinoin. Doctors may not prescribe more than a 30 day supply. A new prescription may not be written for at least 30 days. Pharmacies are also under similar restriction. No more than a 30 day supply may be filled. There is also a 7 day window in which the medication must be picked up at the pharmacy; if the prescription has not been filled within the 7th day of the doctor handing the patient the prescription, it is then voided and can not be filled/sold. If the original prescription is lost, or pick-up window is missed, the patient must wait 30 days without any medication. Doctors and pharmacists must also verify written prescriptions in an online system before patients may fill the prescription. This sequence of requirements can make it very difficult for patients to receive and take isotretinoin on the prescribed schedule. Many patients are forced to wait several days without medication. Moreover, delays in treatment result in some woman taking isotretinoin for longer periods, which is a further burden and can result in more side effects due to longer exposure.
The website includes a privacy statement, which discusses what information is collected, how it is used, and where questions can be directed. Requirements of the program include monthly pregnancy tests.
Participation of Males and Non-Child Bearing Females
The iPLEDGE Program requires the participation of both males and FnCBPs, and this has been a subject of criticism over the course of the program's lifetime. Participation is required to ensure that these two groups understand the basic requirements, as sharing of medication with women who can get pregnant is a real concern. The Program requirements for males and FnCBPs are more lenient, as those two groups do not need to take either pregnancy or comprehension tests on a monthly basis, and their prescription window is 30 days from the office visit, rather than seven days.
Criticisms of the iPLEDGE website
Some criticisms of the iPLEDGE website include the website provides no information about who administers the site or how patients' private information is secured. Another criticism is that a website is not an effective pregnancy prevention program.
The program was mandated by the FDA despite criticism from practicing medical doctors that its cumbersome nature would make the drug unavailable to deserving patients. In practice, the website has presented many problems to physicians; once information is entered, it can be difficult or impossible to change or correct it. If there is an error, the patient is locked out for 30 days and cannot receive the medication. Problems are common and take days to correct. Technical assistance by phone is available via a toll free number. The iPLEDGE presumes that the woman will not be honest about her sexual activities by requiring the pregnancy test; but at the same time assumes she will by the pledge be trustworthy to either use contraceptives or not engage in sex.
Although the goal of the program is to prevent pregnancies, male patients must also use the same program even though the questions and "Pledge" are geared towards females. This includes promising that they will not get pregnant as part of the iPLEDGE questioning. There has been no link to birth defects from Accutane associated with males using the drug, though male sexual dysfunction has been suggested by at least one study. However, this is not acknowledged as a side effect in the official literature accompanying the medication.
- "Ipledgeprogram.com Site Info". Alexa Internet. Retrieved 2014-04-01.
- WebMD Medical News: "FDA OKs Tighter Controls for Accutane." News release, John Wiley & Sons, Inc.
- WebMD Medical News: "Accutane's Pregnancy Risk: Are Women Aware?" Miranda Hitti. Oct. 14
- Robertson, Julia; et al. (November 2005). "A survey of pregnant women using isotretinoin". Birth Defects Research (Part A): Clinical and Molecular Teratology 73 (11): 881–887. doi:10.1002/bdra.20197. PMID 16228976. Retrieved 2009-02-07 Almost 1/4 of the women surveyed (24%; 8/34) did not recall having contraception counselling before starting their medications. Once therapy was initiated, 62% (21/34) recalled using a birth control method, but only 29% (6/21) recalled using 2 forms of birth control, as specified by the voluntary pregnancy prevention programs. Monthly pregnancy tests were not always conducted during treatment, as recalled by the surveyed women (56%; 19/34). As many as 24% (8/34) of the women surveyed recalled that they were not screened using 2 pregnancy tests before receiving a prescription, another recommendation of the programs. Only a small number of the women (30%; 6/20) in the United States recalled being enrolled in any manufacturers' voluntary pregnancy prevention survey. . . Results demonstrate that essential components of voluntary pregnancy prevention programs were not consistently followed, which resulted in fetal exposures..
- WebMD Medical News: "FDA Panel Urges Stricter Acne Drug Tracking; Women Still Having Risky Pregnancies While Taking Accutane", Feb 27, 2004
- Tirado Sánchez A; León Dorantes G. (Nov–Dec 2005). "[Erectile dysfunction during isotretinoin therapy]". Actas urologicas españolas. 29 (10): 974–6. PMID 16447596.
- [Erectile dysfunction during isotretinoin therapy] 29 (10). 2005. pp. 974–6. PMID 16447596.
- ipledgeprogram.com The official iPledge program web site.
- FDA press release about the program
- Information from the CDC CDC and the March of Dimes about Accutane and birth defects
- Medscape Medical News, Dermatologists Frustrated With Problematic iPledge Program, AAD 64th Annual Meeting. Focus session, March 6, 2006
- The iPLEDGE Program Patient Introductory Brochure iPLEDGE Committed to Pregnancy Prevention