U.S. regulators plan an extensive study of blood-pressure drugs that generate almost 40 million prescriptions a year, after receiving thousands of complaints from doctors and patients.
Generics of AstraZeneca Plc’s extended release Toprol XL make up about 90 percent of physicians’ orders for the drug. The copycat drugs are made by Wockhardt Ltd. and Dr. Reddy’s Laboratories Ltd., both of which are based in India, and Mylan Inc. and Actavis Plc in the U.S.
Complaints against the drug, known generically as metoprolol succinate, cite both a lack of effectiveness and troublesome side effects, according to a review of 3,425 adverse incident reports by Bloomberg News. While the reports generally don’t identify manufacturers, the Food and Drug Administration tests will focus on whether the copies are chemically the same as the original, the funding request shows.
“The FDA will continue to monitor and review available safety and other information related to metoprolol succinate extended release products and take any further action as appropriate,” said Sandy Walsh, a spokeswoman, in an e-mail.
The plan to test metoprolol succinate expands on a $20 million FDA testing program begun in September. The agency has been ramping up its effort to improve the safety and quality of generic drugs, particularly from abroad, during the last year. The adverse incidents reported to the agency, obtained under a Freedom of Information Act, include reports over five years beginning in March 2009.
Adverse incident reports can be sent to the FDA by companies, medical professionals and patients. While they are largely unverified by the agency, they can sometimes serve as a first-alert that U.S. regulators should look more closely at an individual product.
In this case, the FDA undertook initial tests that showed generic forms of the drugs dissolved properly. The agency is now in the process of contracting with independent researchers to complete a more extensive study, Walsh said. The agency has also re-evaluated the criteria that formed the basis for approval of the generic products, she said.
Wockhardt, the seventh-largest drugmaker in India by revenue, controlled about 26 percent of the U.S. market for metoprolol succinate it made in its Chikalthana, India-based plant, according to the investment bank Needham & Co. The facility was banned from sending drugs to the U.S. on Nov. 26, 2013, one of more than 20 in India hit with U.S. bans since the beginning of last year. The FDA cited unsanitary conditions and workers that manipulated quality tests.
Dominic D’Souza, a spokesman for Wockhardt, didn’t respond to a call on his mobile phone and an e-mail seeking comment. A representative for Dr. Reddy’s wouldn’t immediately comment while spokesmen for Actavis and Mylan declined to comment.
The existing testing program includes 19 studies on generic copies of drugs such as immune-suppression medications and inhaled allergy treatments. Some of the research will be done as early as September while other studies may take several years to complete, the agency has said.
The added research into metoprolol succinate will begin as early as September and can last as long as three years, according to the FDA request.
Legislation passed in 2012 allows the FDA to collect fees from generic-drug companies to help fund new product reviews and increased inspections overseas. The agency began the widespread research program on generics last year that will last at least through 2017 using some of the money raised.
The FDA began its investigation into the generic blood pressure drug after Harry Lever, a cardiologist at the Cleveland Clinic, expressed concern to the FDA in 2012 that the pills he was prescribing worked inconsistently. In February, Lever discussed his issues with generic drugs during a congressional briefing.
Novartis AG’s Sandoz unit took its metoprolol succinate off the market after it recalled more than 6 million bottles in 2008 when it was discovered the product might not meet certain specifications, according to the FDA’s website.
Generic drugmakers don’t copy branded medicines’ extended-release technology like they do the drug. Patents on the technology can outlast the patent on the original medication causing generic firms to design an extended-release system around the patent, said David Rosen, a partner at Foley & Lardner in Washington, who was a senior FDA official working on generics in the 1980s.
“It’s an important issue and we want to make sure these products perform in the way they’re supposed to perform,” Rosen said in a telephone interview.