MIDODRINE HYDROCHLORIDE- midodrine hydrochloride tablet
Global Pharmaceuticals, Division of Impax Laboratories Inc.
Rx only
WARNING
Because midodrine hydrochloride 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 midodrine hydrochloride 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 midodrine hydrochloride, principally improved ability to carry out activities of daily living, have not been verified.
DESCRIPTION
Name: Midodrine Hydrochloride Tablets
Dosage Form: 2.5 mg, 5 mg and 10 mg tablets for oral administration
Active Ingredient: Midodrine hydrochloride
Inactive Ingredients: Microcrystalline Cellulose, NF; Corn Starch, NF; Colloidal Silicon Dioxide, NF; Magnesium Stearate, NF; Talc, USP; FD&C Yellow No. 6 (5 mg tablet); Lake Blend Green (10 mg tablet).
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 -((beta)-hydroxy-2,5-dimethoxyphenethyl)acetamide monohydrochloride BAN, INN, JAN: Midodrine. Molecular Formula: C12 H18 N2 O4 HCl; 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
Midodrine hydrochloride 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 midodrine HCl 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. Midodrine HCl has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure. DOSAGE AND ADMINISTRATION
The recommended dose of midodrine hydrochloride tablets is 10 mg, 3 times daily. Dosing should take place during the daytime hours when the patient needs to be upright, pursuing the activities of daily living. A suggested dosing schedule of approximately 4-hour intervals is as follows: shortly before or upon arising in the morning, midday, and late afternoon (not later than 6 PM). Doses may be given in 3-hour intervals, if required, to control symptoms, but not more frequently. Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (about 45%) at this dose. In order to reduce the potential for supine hypertension during sleep, midodrine HCl tablets should not be given after the evening meal or less than 4 hours before bedtime. Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established. Because of the risk of supine hypertension, midodrine HCl tablets should be continued only in patients who appear to attain symptomatic improvement during initial treatment.
The supine and standing blood pressure should be monitored regularly, and the administration of midodrine HCl tablets should be stopped if supine blood pressure increases excessively.
Because desglymidodrine is excreted renally, dosing in patients with abnormal renal function should be cautious; although this has not been systematically studied, it is recommended that treatment of these patients be initiated using 2.5 mg doses.
Dosing in children has not been adequately studied.
