Abbott ADHD Drug Cylert Withdrawn But FDA Stops Short Of Immediate Recall

FDA is opting for a phased withdrawal of pemoline products (Abbott's Cylert and generics) rather than a full recall to give patients time to transition to alternate therapies.

The agency announced the withdrawal of the ADHD drug Oct. 24. Pemoline has been associated with liver failure.

"Given the availability of multiple other drug treatments for attention deficit hyperactivity disorder, including one that is not scheduled and several products that can be given once a day, FDA has concluded that the risk of liver failure with this drug outweighs the potential benefits," the agency said in an alert for healthcare professionals posted on its website.

FDA has made Cylert "available through pharmacies and wholesalers until supplies are exhausted," after which "no additional product will be available."

The agency has not issued a formal notice of withdrawal in the Federal Register.

In its alert, FDA recommends that healthcare professionals who prescribe Cylert or generic pemoline "transition their patients to an alternative therapy."

Abbott stopped marketing Cylert in May, citing declining sales. The company said the discontinuation was not due to issues raised in a petition to FDA by Public Citizen that asserted labeling revisions had been ineffective in reducing the risk of liver toxicity associated with the drug (¹ , p. 8).

Public Citizen now criticizes the agency's phased withdrawal for lacking "any sense of urgency." In an Oct. 24 letter, the consumer advocacy group pressed FDA for an "immediate recall of these dangerous products."

"Even though Abbott announced in the spring that it would no longer market or sell Cylert, almost 10,000 of these prescriptions were for its version of the drug since April," the group said. Between Public Citizen's petition filed in March, and the end of September, more than 60,000 prescriptions for pemoline were filled in the U.S., the group said.

A phased withdrawal of pemoline does not pose a safety risk because patients using the drug have been stabilized on it for years, FDA said. Cylert was approved in 1975; generics entered the market in 1999.

Six firms - Amide, Teva, Mallinckrodt, Vintage, Watson and Sandoz - hold ANDAs for generic pemoline; five companies voluntarily stopped marketing pemoline shortly after Abbott ceased marketing the brand version. Sandoz had complied with FDA's request to stop marketing pemoline by Oct. 7.

"All generic companies have agreed to stop sales and marketing of this product (pemoline tablets and chewable tablets)," FDA's alert says.

Cylert labeling added a "black box" warning in 1996 describing it as a second-line therapy for ADHD due to its potential for "life threatening hepatic failure." A patient consent requirement and a liver monitoring program recommendation were added to labeling in 1999.

FDA's alert notes that despite labeling revisions, "a risk of liver failure remains." The agency reports one new case of pemoline-associated liver failure since the 1999 "black box" revisions.

In total, the agency is aware of 13 reports of liver failure resulting in liver transplant or death, "usually within four weeks of onset of signs and symptoms of liver failure."

"Although the absolute number of reported cases of liver failure with pemoline is not large, the reporting rate for liver failure with pemoline is 10 to 25 times greater than the background rate of liver failure in the general population," FDA said.

FDA is conducting a post-marketing safety analysis of all ADHD products; it is expected to present the results to the Pediatric Advisory Committee in early 2006.

Concerns about cardiovascular events with ADHD products were raised with the Canadian suspension of Shire's Adderall XR (extended-release amphetamine) in February (² (Also see "Shire Adderall XR Sales Suspended In Canada; FDA Stands By “Black Box”" - Pink Sheet, 14 Feb, 2005.), p. 7). FDA also issued a public health advisory regarding suicidal thinking for Lilly's Strattera (atomoxetine) (³ (Also see "ADHD Suicidal Thinking Health Advisory Limited To Lilly’s Strattera" - Pink Sheet, 3 Oct, 2005.), p. 8).