Pregnancy
Pregnancy Category C. ProAmatine® increased the rate of embryo resorption, reduced fetal body weight in rats and rabbits, and decreased fetal survival in rabbits when given in doses 13 (rat) and 7 (rabbit) times the maximum human dose based on body surface area (mg/m2). There are no adequate and well-controlled studies in pregnant women. ProAmatine® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. No teratogenic effects have been observed in studies in rats and rabbits.

Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ProAmatine® is administered to a nursing woman.

Pediatric Use
Safety and effectiveness in pediatric patients have not been established.

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 
 Placebo
n=88  Midodrine
n=82 
Event # of reports % of patients # of reports % of patients
Total # of reports  22 
 77 
 
Paresthesia1 4  4.5  15  18.3 
Piloerection  0  0  11  13.4 
Dysuria2 0  0  11  13.4 
Pruritis3 2  2.3  10  12.2 
Supine hypertension4 0  0  6  7.3 
Chills  0  0  4  4.9 
Pain5 0  0  4  4.9 
Rash  1  1.1  2  2.4 

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

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 ProAmatine® 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-receptor