PROAMATINE - midodrine hydrochloride tablet 
Physicians Total Care, Inc.
Warning: Because ProAmatine® can cause marked elevation of supine blood pressure, it should be used in patients whose lives are considerably impaired despite standard clinical care. The indication for use of ProAmatine® in the treatment of symptomatic orthostatic hypotension is based primarily on a change in a surrogate marker of effectiveness, an increase in systolic blood pressure measured one minute after standing, a surrogate marker considered likely to correspond to a clinical benefit. At present, however, clinical benefits of ProAmatine®, principally improved ability to carry out activities of daily living, have not been verified.

DESCRIPTION
Name: ProAmatine®(midodrine hydrochloride) Tablets

Dosage Form: 2.5-mg, 5-mg and 10-mg tablets for oral administration

Active Ingredient: Midodrine hydrochloride, 2.5 mg, 5 mg and 10 mg

Inactive Ingredients: Colloidal Silicone Dioxide NF, Corn Starch NF, FD&C Blue No. 2 Lake (10-mg tablets), FD&C Yellow No. 6 Lake (5-mg tablet), Magnesium Stearate NF, Microcrystalline Cellulose NF, Talc USP

Pharmacological Classification: Vasopressor/Antihypotensive

Chemical Names (USAN: Midodrine Hydrochloride): (1) Acetamide, 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]-monohydrochloride, (±)-;

(2) (±)-2-amino-N-(β-hydroxy-2,5-dimethoxyphenethyl)acetamide monohydrochloride

BAN, INN, JAN: Midodrine

Structural formula:

Molecular formula: C12H18N2O4HCl; Molecular Weight: 290.7

Organoleptic Properties: Odorless, white, crystalline powder

Solubility: Water: Soluble

Methanol: Sparingly soluble

pKa: 7.8 (0.3% aqueous solution) pH: 3.5 to 5.5 (5% aqueous solution)

Melting Range: 200 to 203°C

CLINICAL PHARMACOLOGY
Mechanism of Action: ProAmatine® forms an active metabolite, desglymidodrine, that is an alpha1-agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. Desglymidodrine does not stimulate cardiac beta-adrenergic receptors. Desglymidodrine diffuses poorly across the blood-brain barrier, and is therefore not associated with effects on the central nervous system.

Administration of ProAmatine® results in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension of various etiologies. Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10-mg dose of midodrine, with some effect persisting for 2 to 3 hours. ProAmatine® has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure.

Pharmacokinetics:ProAmatine® is a prodrug, i.e., the therapeutic effect of orally administered midodrine is due to the major metabolite desglymidodrine, formed by deglycination of midodrine. After oral administration, ProAmatine® is rapidly absorbed. The plasma levels of the prodrug peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about 3 to 4 hours. The absolute bioavailability of m