Companies failed to provide evidence of clinical benefit of midodrine hydrochloride

SILVER SPRING, Md., Aug. 16 /PRNewswire-USNewswire/ -- The U.S. Food and Drug Administration today proposed to withdraw approval of the drug midodrine hydrochloride, used to treat the low blood pressure condition orthostatic hypotension, because required post-approval studies that verify the clinical benefit of the drug have not been done.

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Patients who currently take this medication should not stop taking it and should consult their health care professional about other treatment options.

The drug, marketed as ProAmatine by Shire Development Inc. and as a generic by others, was approved in 1996 under the FDA's accelerated approval regulations for drugs that treat serious or life-threatening diseases. That approval required that the manufacturer verify clinical benefit to patients through post-approval studies.

To date, neither the original manufacturer nor any generic manufacturer has demonstrated the drug's clinical benefit, for example, by showing that use of the drug improved a patient's ability to perform life activities.

Orthostatic hypotension is a condition in which patients are unable to maintain blood pressure in the upright position and, therefore, become dizzy or faint when they stand up.

"We've worked continuously with the drug companies to obtain additional data showing the drug's clinical benefits to patients," said Norman Stockbridge, M.D., director of the Division of Cardiovascular and Renal Drugs in the FDA's Center for Drug Evaluation and Research. "Since the companies have not been able to provide evidence to confirm the drug's benefit, the FDA is pursuing a withdrawal of the product."

The FDA today issued a Proposal to Withdraw Marketing Approval and Notice of Opportunity for a Hearing to the companies that manufacture midodrine. This is the first time the agency has issued such a notice for a drug approved under the FDA's accelerated approval regulations. Shire, the maker of the brand name drug, must respond to the FDA in writing within 15 days to request a hearing. If the company fails to do so, the opportunity for a hearing will be waived. Sponsors of generic versions of midodrine will have 30 days to submit written comments on the notice. If, after considering any relevant submissions, the FDA continues to believe that withdrawal of approval is warranted, approval of all midodrine products, including generic versions, will be withdrawn.

Generic versions of the drug are made by Apotex Corp., Impax Laboratories Inc., Mylan Pharmaceuticals, Sandoz Inc., and Upsher-Smith Laboratories.

Under accelerated approval, a drug company may obtain approval of a drug used to treat a serious or life-threatening disease or condition based upon a surrogate endpoint. A surrogate endpoint is a clinical marker, such as a positive effect on blood pressure, believed to predict actual clinical benefits such as improved survival or decreased severity of the disease.

Drug companies that obtain approval under this program are required to conduct additional clinical trials after approval to confirm the drug's benefit. If those trials fail to confirm clinical benefit to patients, or if the companies do not pursue the required confirmatory trials with due diligence, the FDA can withdraw approval of the drug using expedited procedures.

According to a database used by the FDA, about 100,000 patients in the United States filled prescriptions for brand or generic forms of midodrine in 2009.

The agency is working with the drug manufacturers to develop an expanded-access program to allow patients who currently receive the drug to continue to receive it. On a case-by-case basis, expanded-access programs allow the use of a drug outside of a clinical trial to treat patients with a serious or immediately life-threatening disease or a condition that has no comparable or satisfactory alternative treatment options.

For more information:

Notice of Opportunity for a Hearing

http://www.regulations.gov/search/Regs/home.html#searchResults?Ne=11+8+8053+8098+8074+8066+8084+1&Ntt=FDA-2007-N-0475&Ntk=All&Ntx=mode+matchall&N=0

Access to Investigational Drugs Outside of a Clinical Trial http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/AccesstoInvestigationalDrugs/ucm176098.htm

Media Inquiries: Sandy Walsh, 301-796-4669, sandy.walsh@fda.hhs.gov

Consumer Inquiries: 888-INFO-FDA

SOURCE U.S. Food and Drug Administration