INDICATIONS AND USAGE Midodrine Hydrochloride Tablets, USP are indicated for the treatment of symptomatic orthostatic hypotension (OH).

Because Midodrine Hydrochloride Tablets, USP can cause marked elevation of supine blood pressure (BP>200 mmHg systolic), it should be used in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations.

The indication is based on Midodrine Hydrochloride Tablets, USP effect on increases in 1-minute standing systolic blood pressure, a surrogate marker considered likely to correspond to a clinical benefit.

At present, however, clinical benefits of Midodrine Hydrochloride Tablets, USP principally improved ability to perform life activities, have not been established.

Further clinical trials are underway to verify and describe the clinical benefits of Midodrine Hydrochloride Tablets, USP.

After initiation of treatment, Midodrine Hydrochloride Tablets, USP should be continued only for patients who report significant symptomatic improvement.

WARNINGS Supine Hypertension: The most potentially serious adverse reaction associated with Midodrine hydrochloride therapy is marked elevation of supine arterial blood pressure (supine hypertension).

Systolic pressure of about 200 mmHg were seen overall in about 13.4% of patients given 10 mg of Midodrine hydrochloride.

Systolic elevations of this degree were most likely to be observed in patients with relatively elevated pre-treatment systolic blood pressures (mean 170 mmHg).

There is no experience in patients with initial supine systolic pressure above 180 mmHg, as those patients were excluded from the clinical trials.

Use of Midodrine hydrochloride in such patients is not recommended.

Sitting blood pressures were also elevated by Midodrine hydrochloride therapy.

It is essential to monitor supine and sitting blood pressures in patients maintained on Midodrine hydrochloride.

Uncontrolled hypertension increases the risk of cardiovascular events, particularly stroke.

ADVERSE REACTIONS The most frequent adverse reactions seen in controlled trials were supine and sitting hypertension; paresthesia and pruritus, mainly of the scalp; goosebumps; chills; urinary urge; urinary retention and urinary frequency.

The frequency of these events in a 3-week placebo-controlled trial is shown in the following table: Adverse Events 1 Includes hyperesthesia and scalp paresthesia 2 Includes dysuria (1), increased urinary frequency (2), impaired urination (1), urinary retention (5), urinary urgency (2) 3 Includes scalp pruritus 4 Includes patients who experienced an increase in supine hypertension 5 Includes abdominal pain and pain increase Placebo n=88 Midodrine n=82 Event #of reports % of patients #of reports % of patients Total #of reports 22 77 Paresthesia 1 4 4.5 15 18.3 Piloerection 0 0 11 13.4 Dysuria 2 0 0 11 13.4 Pruritis 3 2 2.3 10 12.2 Supine hypertension 4 0 0 6 7.3 Chills 0 0 4 4.9 Pain 5 0 0 4 4.9 Rash 1 1.1 2 2.4 Less frequent adverse reactions were headache; feeling of pressure/fullness in the head; vasodilation/flushing face; confusion/thinking abnormality; dry mouth; nervousness/anxiety and rash.

Other adverse reactions that occurred rarely were visual field defect; dizziness; skin hyperesthesia; insomnia; somnolence; erythema multiforme; canker sore; dry skin; dysuria; impaired urination; asthenia; backache; pyrosis; nausea; gastrointestinal distress; flatulence and leg cramps.

The most potentially serious adverse reaction associated with Midodrine hydrochloride therapy is supine hypertension.

The feelings of paresthesia, pruritus, piloerection and chills are pilomotor reactions associated with the action of midodrine on the alpha-adrenergic receptors of the hair follicles.

Feelings of urinary urgency, retention and frequency are associated with the action of midodrine on the alpha-receptors of the bladder neck.