FDA OKs Tighter Controls for Accutane

'iPLEDGE' Program Aims to Prevent Use of Acne Drug During Pregnancy

Aug. 12, 2005 -- The FDA has approved a plan to help prevent pregnant women from using the prescription acne drug Accutane and its generic versions.

Isotretinoin (Accutane and its generics) is a highly effective drug, but it carries a significant risk of birth defects if taken during pregnancy, according to an FDA news release.

That risk has long been noted on the acne drug's information packets. Now, drug companies are launching a new program to drive the message home to doctors, patients, pharmacies, and drug wholesalers.

'Long Overdue' Change?

"This is a system that has been long in the works, and, many would say, is long overdue," Sandra Kweder, MD, told reporters in a conference call. Kweder is the deputy director of the Office of New Drugs at the FDA's Center for Drug Evaluation and Research.

"The responsibilities for ensuring that fetuses are not exposed to this medicine is enormous and are shared by everyone who participates in distribution of the drug, or prescribing the drug, or taking the drug," says Kweder.

An FDA advisory committee recommended changing the drug's risk management in February 2004. Since then, the FDA and all involved drug companies have been hammering out the details. In November 2004 the drug companies announced that they had reached an agreement; a plan called iPLEDGE is the result of those efforts.

About the Program

The iPLEDGE plan requires virtually everyone involved with prescribing, supplying, or using the drug to register and accept certain responsibilities.

For women of childbearing age, those responsibilities include:

  • Signing an informed consent form in their doctor's office.
  • Personally registering with iPLEDGE.
  • Getting two negative pregnancy tests within seven days of starting the drug.
  • Agreeing to use two forms of birth control.
  • Getting a negative pregnancy test within seven days of seeking their monthly drug refill.

The pregnancy tests must be done in a doctor's office or at a lab. Home pregnancy tests do not count.

Men also have to sign an informed consent form and be registered through their doctor's office, but they don't need to personally sign up with iPLEDGE or follow the plan's pregnancy-related rules.

"This is a drug that's taken only for about four to six months," notes Kweder.

Doctors, Patients, Pharmacies Must Register

Doctors, pharmacies, and wholesalers must also register with iPLEDGE and take on certain duties.

For instance, the prescribing doctor must counsel patients about the drug's risks, give them an informed consent form, register with iPLEDGE, note patients taking the drug in the iPLEDGE system, and receive patients' pregnancy test results.

Pharmacies must log on to iPLEDGE and check that everything is in order before filling a prescription for the drug for women of childbearing age.

Wholesale companies must agree only to give the drug to pharmacies that register with iPLEDGE.

Close Monitoring

The drug companies behind iPLEDGE have pledged to watch the system closely. Pharmacies that don't comply could be cut off from receiving the drug, and the drug's Internet availability will also be monitored, says Kweder.

All four companies making the drug -- plus one distributor -- are involved in iPLEDGE, says Kweder. Those companies include:

  • Roche, manufacturer of Accutane.
  • Genpharm, manufacturer of Amnesteem, which is distributed by Mylan/Bertek.
  • Ranbaxy Pharmaceuticals, manufacturer of Sotret.
  • Barr Laboratories, manufacturer of Claravis.

Any companies that start making other generic versions of the drug must join iPLEDGE, says Kweder.

Changes to Drug's Psychiatric Notes

Accutane and generic versions of the drug may cause depression, psychosis, and, rarely, suicidal thinking, suicide attempts, suicide, and aggressive and/or violent behaviors. However a small study earlier this year failed to show a link between the drug to severe depression or suicide.

The FDA has approved changes to the drug's existing warnings, patient information, and informed consent. The goal is to help patients and prescribers "better identify and manage the risks of psychiatric symptoms and depression before or after prescribing isotretinoin," states the FDA's news release.

"The specific intent of the iPLEDGE program is to prevent pregnancy, but this is a drug that has a number of potential side effects including the concern about psychiatric effects, but others as well. The intent is that patients be educated about all of the potential risks as part of their participation in taking the medicine," says Kweder.

To Register for iPLEDGE

Starting on Aug. 22, doctors, patients, and pharmacies can get program information and register with iPLEDGE online at or by telephone ((866) 495-0654).

Starting Nov. 1, wholesalers and pharmacies will have to register with iPLEDGE to obtain isotretinoin from a manufacturer.

By Dec. 31, all patients and prescribers (doctors) must register and comply with requirements for office visits, counseling, birth control, and other responsibilities.

FDA: Report All Pregnancy Exposures to Drug

A reporting and collection system for serious side effects associated with isotretinoin has also been implemented.

All pregnancy exposures to isotretinoin must be reported immediately to the FDA's MedWatch system ((800) FDA-1088) and to iPLEDGE online or by phone at (866) 495-0654.

Statement From Roche

In a statement emailed to WebMD, the drug company Roche states that it is "pleased" with iPLEDGE's approval and pledges to keep working with the FDA and "support ongoing efforts to prevent, to the extent possible, the risk of fetal exposure to isotretinoin."

Show Sources

SOURCES: News release, FDA. Sandra Kweder, MD, deputy director, Office of New Drugs, FDA Center for Drug Evaluation and Research. Roche: "Accutane: Complete Product Information." Emailed statement, Roche.

© 2005 WebMD, Inc. All rights reserved. View privacy policy and trust info