Generic A.D.H.D. Drug, Not Equivalent to the Brand, Is in Use Anyway

When Dr. Louis Kraus, a chief of child psychiatry at a hospital in Chicago, writes prescriptions for patients who have attention-deficit hyperactivity disorder, he often chooses Concerta, an extended-release form of the drug Ritalin that gives patients relief from their symptoms for as long as 12 hours.

He was unconcerned when, a few years ago, pharmacies began substituting lower-cost generic alternatives for brand-name Concerta — after all, generic drugs are widely seen as effective and account for the overwhelming majority of prescriptions filled nationwide.

His feelings changed last November, however, when the
Food and Drug Administration announced that two of the three available Concerta generics, one made by Mallinckrodt Pharmaceuticals and the other by UCB, could no longer be considered the equivalent of the brand and, in most states, could not be automatically substituted by pharmacies for the brand name.

The agency said that although it considered the drugs to be safe, its own lab tests and other analyses suggested that their effectiveness began to wear off much more quickly — after about seven hours. That time frame is important, because the pill can be taken only once a day.

The agency allowed the companies to continue selling their drugs, but gave them six months to either prove the drugs were equivalent, or remove them from the market.

Seven months later, the deadline has passed and the drugs are still being sold. Major pharmacies like CVS and Rite Aid continue to stock them, and together the drugs have managed to hold on to about 30 percent of the market. (A third product, sold by Actavis, was found to be equivalent to the brand. Johnson & Johnson makes Concerta as well as the Actavis generic.)
“This has gone on for months,” said
Dr. Kraus, who is the chief of child psychiatry at Rush University Medical Center. The lack of action by the F.D.A., he said, has undermined his faith in generics. “We’re as much in the black as the patients are. And then we find this out, and it’s really frightening.”

UCB has said it submitted new information last week that will show it is equivalent to Concerta, although it has not shared that information publicly. But Mallinckrodt Pharmaceuticals has taken a different tack: It is challenging the agency’s decision in court. Both companies say they have no plans to withdraw their products.

A spokeswoman for the F.D.A. declined to comment because of the Mallinckrodt lawsuit.

In part, the dispute reflects the controversy around the ability of generic companies to reproduce extended-release drugs, which require more technical expertise to manufacture. The F.D.A. has said it is looking more closely at extended-release generics and
has set aside $20 million to test generics for safety and quality. Attention-deficit drugs were among the agency’s initial targets.

When Concerta was approved in 2000, it was welcomed by doctors because it eliminated the need for patients to take Ritalin three times a day. Previous efforts at developing long-acting forms of the drug had not been as successful. With Concerta, parents could give a child a pill before the child left for school, eliminating midday trips to the school nurse’s office for a new dose.

Concerta’s secret
was the way that it released the drug: The pill absorbed fluid as it passed through the body, and pumped the active drug out of a laser-cut hole.

Under F.D.A. rules, generic companies do not need to use the same mechanisms to produce copycat versions of long-acting drugs. The manufacturers must instead prove that their products release the drug into the body at the same rate as the brand-name drug. The Mallinckrodt and UCB products use different techniques, which may account for the shorter effectiveness.

When word of the F.D.A.’s November decision spread, many Wall Street analysts expected that sales of the two drugs would plummet or that Mallinckrodt and UCB would follow the path of the drug maker Teva, which in 2012
withdrew its version of an extended-release version of Wellbutrin, an antidepressant, after the F.D.A. made a similar decision about its product. Mallinckrodt’s stock dropped 7 percent at the time, but has since rebounded.

“It’s the first time we’re seeing something exactly like this,” said Ronny Gal, an analyst with Sanford C. Bernstein & Company. “I kind of thought the F.D.A. would tell them to go away. They haven’t.”

Instead, Mallinckrodt went on the offensive. And Actavis, now the only approved substitute for Concerta, raised its prices.

Dr. Kraus, the child psychiatrist, said he still fielded regular calls from pharmacies and some insurers asking him to change his prescriptions so they can dispense the cheaper generics — drugs that he considers inferior. “I’m enraged about it,” Dr. Kraus said.

Representatives for CVS and Rite Aid said they sell all three generic versions and noted that the F.D.A. has said they are safe. A spokesman for CVS, Michael J. DeAngelis, denied that the company was directing pharmacies to ask doctors to switch their prescriptions. He would not comment on suggestions by some that pharmacies and insurers are motivated to sell the cheaper brands because they reap financial benefits from doing so. He said CVS was dispensing more of the Actavis product than the other two versions.

Rite Aid would not comment on its financial arrangements with the generic companies, or on whether its pharmacists were asking doctors to switch prescriptions.

A spokeswoman for Walgreens said the Actavis product had been its preferred generic since 2011, although it continues to stock the other two versions because some doctors write prescriptions for them; more than 99 percent of its extended-release prescriptions were filled with the Actavis product in May.

In November, Actavis held about 50 percent of the market for generic Concerta, according to an analysis Mr. Gal provided. As of May, that share had grown to 70 percent, but the two other products still hold a significant portion of the market.

Mallinckrodt’s chief executive, Mark Trudeau, told investors in May that he expected to keep the product on the market for the “foreseeable future.”
“It’s very puzzling to me,” said Dr. Harry Lever, a cardiologist at the Cleveland Clinic who has become an advocate for improving the quality of generic drugs. “If the F.D.A. rules it’s not the same, how can it be sold? I don’t understand the rationale for that happening.”

Mr. Gal said the agency’s lack of action had created a bizarre secondary market for the drugs.

“From a regulatory standpoint, it’s a really bad idea to create an additional market for a drug that’s not exactly the same, but in the ballpark,” Mr. Gal said. “You’re a regulator. Regulate.”

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