The FDA (Food and Drug Administration, USA) has recommended withdrawing the approval of ProAmatine (midodrine hydrochloride), a Shire Development Inc. medication for the treatment of orthostatic hypotension – a temporary drop in blood pressure (hypotension), usually due to suddenly standing up; when standing up the patient becomes dizzy or faints. The FDA says that post-approval studies that verify the clinical benefit of the medication have not been done.

The FDA says that patients who are presently taking midodrine hydrochloride should not stop, but should consult their doctor about alternative treatment options.

Midodrine hydrochloride (ProAmatine) was approved in 1996 under the FDA’s accelerated approval regulation for medications for the treatment of serious or life-threatening diseases. The approval was on the condition that the manufacturer, Shire Development Inc, verify clinical benefits to patients through post-approval studies.

Since 1996, neither the original manufacturer no any generic one has demonstrated the drug’s clinical excellence, says the FDA. An example would be a study that shows that using the drug improved the patient’s ability to carry out life activities.

Norman Stockbridge, M.D., director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research, said:

We’ve worked continuously with the drug companies to obtain additional data showing the drug’s clinical benefits to patients. 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. It is the first time a notice of this kind has been issued for a drug that was approved under the FDA’s accelerated approval regulations.

The FDA has told Shire Development Inc., the maker of ProAmatine – the brand name drug – to respond within 15 days in writing to request a hearing. If Shire fails to do this 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.

The FDA wrote on its web site:

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that withdrawal of approval is warranted, approval of all midodrine products, including generic versions, will be withdrawn.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 midodrine hydrochloride are manufactured by Apotex Corp., Impax Laboratories Inc., Mylan Pharmaceuticals, Sandoz Inc., and Upsher-Smith Laboratories.

Pharmaceutical companies that obtain approval of a drug under the accelerated approval program must carry out additional clinical trials after approval to confirm the medication’s benefit.

The FDA writes:

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.

The FDA believes approximately 100,000 American patients 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.

Source: FDA

Written by Christian Nordqvist