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Accutane Warnings

History of Accutane Label Warnings

Before any prescription drug can be legally sold in the United States it must be tested in a series of trials and must be approved by the Food and Drug Administration (FDA).

Once the drug is approved for sale, the FDA continues to monitor its safety through MedWatch, a program that allows consumers and health care professionals to report serious side effects, quality control issues, and medical errors associated with drugs and products regulated by the FDA.

If a side effect is reported that is a large threat to the public, the FDA may issue a warning to the public and/or request that changes be made to the drug's label.

Below is a brief history of the reports and warnings issues for Accutane:

1971

Pharmaceutical company Hoffman La-Roche (Roche) develops Accutane, but decides not to market the drug due to the risks of birth defects.

June, 1982

The Food and Drug Administration (FDA) approves Accutane to treat cases of severe acne where other treatment options have failed.  Shortly after introduction of the drug, the FDA and Roche receive reports of birth defects in infants from mothers taking Accutane.

September, 1983

The consumer advocacy group Public Citizen petitions the FDA to require warning labels on Accutane for the drug’s risk of birth defects and other side effects.

March and October, 1984

The FDA issues physician instructions and requires stronger label warnings for the risk of birth defects from Accutane.

June, 1985

Roche alters the package insert of Accutane to include warnings for “seizures, emotional instability including depression, dizziness, nervousness, drowsiness, malaise, weakness, insomnia, lethargy and paresthesias."

August, 1986

Roche further amends the package literature included with Accutane to disclose:
"Depression has been reported in some patients on Accutane therapy. In some of these patients, this has subsided with discontinuation and recurred with reinstitution of therapy."

May, 1988

An FDA ruling calls for stronger label warnings on Accutane and additional instructions to physicians regarding the risk of birth defects from the drug. The FDA also orders additional studies, including a follow-up survey of patients.

The FDA ignores a recommendation by an advisory committee that Accutane prescription to board-certified dermatologists be restricted.

1990

An FDA memo details the conclusions of a study on Accutane-related birth defects which revealed that Accutane has accounted for 11,000 to 13,000 abortions and 900 to 1,100 birth defects. The FDA comments that, "The magnitude of injury and death has been great and permanent…"

1996

Bad year for Accutane. After an FDA doctor notes two cases of suicide associated with Accutane, the agency initiates a re-evaluation of the drug's potential link to suicide. Some reports describe consistent symptoms in patients with no previous history of depression and no other identifiable reason for their occurrence. Other reports show symptoms beginning with Accutane treatment and resolving soon after treatment has stopped.

The FDA begins the MedGuide program to provide patients with drug information leaflets. Congress allows the FDA to develop MedGuides for 40 drugs with serious side-effects, including Accutane.

Roche attempts to suppress public availability of extensive Accutane documents, including adverse event reports, marketing plans and clinical data, relating to Accutane's risk of birth defects.  They lose in a New Jersey Federal Court.

May, 1997

After a review of the FDA database shows 51 patients taking Accutane had attempted or committed suicide, with only 11 having previously-documented psychiatric illness, FDA medical review officer Dr. Kathyrn O Connell issues memo stating that depression should be added to the boxed warning for Accutane.

August, 1997

The FDA issues a letter to Roche warning them for failing to submit serious adverse event reports in a timely manner. Roche claims the delays of up to 8 years were due to problems with its’ computer systems.

February, 1998

An FDA memo charges that Roche "had not acted in good faith to truly and accurately answer questions relating to Accutane use in women and pregnancy exposure." The memo proposes "active consideration of removal of Accutane from the market." In response, Roche recommends more intensive patient education on the drug's risks of birth defects, including patient materials and informed consent forms.

February 25, 1998

The FDA orders Roche to add a bold-face warning to Accutane's physician package insert:

"WARNINGS - Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events.”

"ADVERSE REACTIONS - In the postmarketing period, a number of patients treated with Accutane have reported depression, psychosis and rarely, suicidal, ideation, suicide attempts and suicide. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy."

In an accompanying press release, Roche claims there is no proof Accutane causes depression and that "teenagers are at particular risk for depression."

March, 1998

Regulating agencies in the U.K. and Ireland order warnings of Accutane's risk of psychiatric disorders similar to those in the United States.

March 5, 1998

The FDA issues a warning letter to Roche ordering that the company cease "false and misleading" advertisements which promote Accutane as an "effective treatment of severe acne... [that] minimizes negative psychosocial effects such as depression and poor self-image."

July, 1998

The FDA learns that Roche failed to disclose that in 1997, French regulatory agencies had already required the addition of a "suicide attempt" warning on Accutane, as well as a 1992-94 study in France associating Accutane with depression.

May 1, 2000

Roche amends the Accutane package label warnings to include: “…Depression and rarely suicidal thoughts, suicide attempts and suicide…”. This is the first time the drug packaging contains full psychiatric warnings.

November, 2002

The FDA amends Accutane label warnings to include Aggression and Violent behavior. The label warning now reads "Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors"

According to MedWatch, an FDA-controlled safety information program, the warnings were the result of "post-marketing safety reports."

August, 2005

The FDA Amends Accutane label warnings under psychiatric Disorders to read: "Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. No mechanism of action has been established for these events. Prescribers should read the brochure, Recognizing Psychiatric Disorders in Adolescents and Young Adults: A Guide for Prescribers of Isotretinoin. Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initation of Accutane therapy, patients and family members should be asked about any history of psychiatric disorder, and at each visit during therapy patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. Signs and symptoms of depression, as described in the brochure (Recognising Psychiatric Disorders in Adolescents and Young Adults) include sad mood, hopelessness, feelings of guilt, worthlessness or helplessness, loss of pleasure or interests in activities, fatigue, difficulty in concentrating, change in sleep pattern, change in weight or appetite, suicidal thoughts or attempts, restlessness, irritability, acting on dangerous impluses, and peristent physical symptoms unresponsive to treatment. Patients should stop Accutane and the patient or a family member should promplty contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression, without waiting until the next visit. Discontinuation of Accutane therapy may be insufficent; further evaluation may be necessary. While such monitoring may be helpful, it may not detect all patients at risk. Patients may report mental health problems or family history of psychiatric disorders. These reports should be discussed with the patient and/or the patient's family. A referral to a mental health professional may be necessary. The physican should consider whether Accutane therapy is appropiate in this setting; for some patients the risks may outweigh the benefits of Accutane therapy.”