IPLEDGE program

iPLEDGE

Type of site	Regulatory/Government
Owner	Food and Drug Administration
URL	ipledgeprogram.com
Commercial	no

The iPLEDGE program is a mandatory distribution program in the United States for isotretinoin (commonly sold under the trade names Accutane, Amnesteem, Claravis or Sotret), 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.

Process

The program is intended to work as follows: First, the doctor prescribing the drug counsels the patient and then enters the patient's medical information—including selected birth control methods if the patient is a woman of child-bearing potential—on the iPLEDGE web site. The dispensing pharmacist then checks the website to ensure that proper birth control precautions have been taken before filling the prescription. 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.

Some Canadian pharmacies will honor US prescriptions, thus providing an alternate source of isotretinoin if US patients are unable to obtain it through FDA-approved procedures.

Recently the iPLEDGE program has been relaxed for males and women of non-childbearing age. Doctors can issue prescriptions a few days early if appointments do not happen to line up with the 30 day window. A lost or unfilled prescription can also be rewritten within 30 days. Mandatory patient counseling and reporting in the online system is still required for all patients.

History

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

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, "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.

Privacy

Some patients complain of the requirements of the iPLEDGE program and say patients must choose between privacy or treatment. Some requirements of the program include regular blood testing every thirty days and regular pregnancy tests every thirty days. Another issue is that of a potential breach in patient/doctor confidentiality. Compliance to the program requires a participating physician to reveal many aspects of a patient's sexual history including STIs, when a patient is registered into the program.

Males and Non-Child Bearing Females

The iPLEDGE program has recently relaxed their procedures regarding non-child bearing patients. However, those patients must still answer online questions monthly (along with their physicians), receive regular blood test, but are not subject to the 7 day window for filling their prescription while taking isotretinoin. Non-child bearing patients have 30 days to fill their prescription.

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.

External links

• ipledgeprogram.com The official iPledge program web site.
• FDA press release about the program
• Information from the CDC CDC and the March of Dimes[1] 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