Public Citizen Petitions FDA to Take Pemoline Off the Market

March 24, 2005

Public Citizen Petitions FDA to Take Pemoline Off the Market

Attention Deficit Hyperactivity Disorder Drug Known to Cause Liver Failure

WASHINGTON, D.C. – Public Citizen today petitioned the U.S. Food and Drug Administration (FDA) to immediately remove pemoline (Cylert), a central nervous system stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD), from the market because it is known to have caused at least 21 cases of liver failure, including 13 resulting in liver transplantation or death.

In its petition, the consumer advocacy organization noted that the drug’s unfavorable risk-to-benefit ratio has led to its withdrawal in the United Kingdom and Canada while the FDA instead opted for two separate black box warning labels that a 2002 FDA study shows were ineffective in reducing the drug’s risks. “In light of this evidence of unique liver toxicity without evidence of unique therapeutic benefit, we contend that the only responsible course of action is to remove this dangerous drug from the market,” states the petition.

Pemoline originally appealed to clinicians because it allowed once-a-day dosing, as opposed to multiple daily doses that might raise logistical problems, especially for children in school during the day. However, due to the development of long-acting formulations of other stimulant medications, this is no longer a unique characteristic, Public Citizen’s petition says. In 2004, approximately 117,000 pemoline prescriptions were filled in the United States.

Reports of liver abnormalities appeared in U.S. clinical trials even before the drug was approved by the FDA in 1975. Between the 1975 approval and 1996, there were 193 adverse drug reactions involving the liver ascribed to pemoline reported to the FDA that involved patients under the age of 20. As of May 1996, there were 13 cases of acute liver failure due to pemoline, 11 of which resulted in death or liver transplantation.

An FDA analysis by Dr. David Graham, who testified at congressional hearings about Vioxx safety concerns, estimated a 16.8-fold increased risk of acute liver failure due to pemoline compared to the general population, assuming no underreporting. Given that adverse events are reported to the FDA about 10 percent of the time, the relative risk for acute liver failure could be closer to 168-fold.

The maker of   pemoline, Abbott Laboratories, challenged the FDA’s conclusion in 1996 that pemoline had “an unfavorable risk to benefit ratio” and should be withdrawn from the market. Abbott was allowed to continue marketing the drug by adding a black box warning and by sending a letter to all U.S. physicians warning about pemoline’s liver toxicity and recommending that it should no longer be considered a first-line therapy for ADHD.

A stronger black box warning urging periodic liver tests was issued in June 1999 as liver failure cases continued to accumulate. An FDA study demonstrated that most physicians were not doing the recommended testing.

“The Food and Drug Administration should immediately ban the sale of pemoline,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “Relatively safe and effective drug treatments exist for ADHD, and since there are no data that demonstrate pemoline has any unique benefit over other drugs, there is no responsible basis for keeping this unacceptably dangerous drug on the market.”

Public Citizen is joined in its petition to the FDA by Dr. Fredric Solomon, clinical professor of psychiatry and behavioral sciences at the George Washington University School of Medicine, who in the course of 42 years of clinical experience has evaluated and cared for hundreds of patients with ADHD.

###

To read Public Citizen’s petition, click here.