Determination That PROAMATINE (Midodrine Hydrochloride) Tablets, 2.5 Milligrams, 5 Milligrams, and 10 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA or Agency) has determined that PROAMATINE (midodrine hydrochloride) tablets, 2.5 milligrams (mg), 5 mg, and 10 mg, were not withdrawn from sale for reasons of safety or effectiveness. This determination allows FDA to approve abbreviated new drug applications (ANDAs) for midodrine hydrochloride tablets, 2.5 mg, 5 mg, and 10 mg, if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT:

Kristiana Brugger, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6262, Silver Spring, MD 20993-0002, 301-796-3601.

SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of drug products under an ANDA procedure. ANDA applicants must, with certain exceptions, show that the drug for which they are seeking approval contains the same active ingredient in the same strength and dosage form as the “listed drug,” which is a version of the drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA).

The 1984 amendments include what is now section 505(j)(7)(A) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)(A)), which requires FDA to publish a list of all approved drugs. FDA publishes this list as part of the “Approved Drug Products With Therapeutic Equivalence Evaluations,” which is known generally as the “Orange Book.” Under FDA regulations, drugs are removed from the list if the Agency withdraws or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).

A person may petition the Agency to determine, or the Agency may determine on its own initiative, whether a listed drug was withdrawn from sale for reasons of safety or effectiveness.

PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, is the subject of NDA 019815, held by Shire Development LLC (Shire), and initially approved on September 6, 1996, under the accelerated approval process (see 21 CFR 314.510). PROAMATINE is indicated for the treatment of orthostatic hypotension. PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, is currently listed in the “Discontinued Drug Product List” section of the Orange Book. Shire no longer markets PROAMATINE in any strength; although there are approved ANDAs referencing NDA 019815, PROAMATINE has been withdrawn from sale.

We have carefully reviewed our files for records concerning the withdrawal of PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, from sale. We have also independently evaluated relevant literature and data for possible postmarketing adverse events. FDA has determined under § 314.161 that PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, were not withdrawn from sale for reasons of safety or effectiveness.

Accordingly, FDA will continue to list PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, in the “Discontinued Drug Product List” section of the Orange Book. We note that, because PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, were approved under the accelerated approval pathway, Shire was required to conduct post-approval studies to verify the clinical benefit of PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg. The clinical benefit of PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, remains subject to verification.

ANDAs that refer to PROAMATINE (midodrine hydrochloride) tablets, 2.5 mg, 5 mg, and 10 mg, may be approved by the Agency as long as they meet all other legal and regulatory requirements for the approval of ANDAs. If FDA determines that labeling for this drug product should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.