Midodrine Hydrochloride (Page 3 of 4)

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 midodrine hydrochloride 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
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
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 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.
To report SUSPECTED ADVERSE REACTIONS contact AvKARE, Inc. at 1-855-361-3993; email drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

Symptoms of overdose could include hypertension, piloerection (goosebumps), a sensation of coldness and urinary retention. There are 2 reported cases of overdosage with midodrine hydrochloride , both in young males. One patient ingested midodrine hydrochloride drops, 250 mg, experienced systolic blood pressure greater than 200 mmHg, was treated with an IV injection of 20 mg of phentolamine, and was discharged the same night without any complaints. The other patient ingested 205 mg of midodrine hydrochloride (41 5-mg tablets), and was found lethargic and unable to talk, unresponsive to voice but responsive to painful stimuli, hypertensive and bradycardic. Gastric lavage was performed, and the patient recovered fully by the next day without sequelae.

The single doses that would be associated with symptoms of overdosage or would be potentially life-threatening are unknown. The oral LD ₅₀ is approximately 30 to 50 mg/kg in rats, 675 mg/kg in mice, and 125 to 160 mg/kg in dogs.

Desglymidodrine is dialyzable.

Recommended general treatment, based on the pharmacology of the drug, includes induced emesis and administration of alpha-sympatholytic drugs (e.g., phentolamine).

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 P.M.). 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 hydrochloride 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 hydrochloride 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 hydrochloride 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.

Blood levels of midodrine and desglymidodrine were similar when comparing levels in patients 65 or older vs. younger than 65 and when comparing males vs. females, suggesting dose modifications for these groups are not necessary.

HOW SUPPLIED

Midodrine hydrochloride tablets, USP 2.5 mg are available for oral administration as white, round, scored tablets, imprinted “APO” on one side and “MID” above bisect “2.5” on the other side. They are supplied as follows:

Bottles of 90 (NDC 42291-560-90)

Midodrine hydrochloride tablets, USP 5 mg are available for oral administration as orange, round, scored tablets, imprinted “APO” on one side and “MID” above bisect “5” on the other side. They are supplied as follows:

Bottles of 90 (NDC 42291-561-90)

Midodrine hydrochloride tablets, USP 10 mg are available for oral administration as light blue, round, scored tablets, imprinted “APO” on one side and “MID” above bisect “10” on the other side. They are supplied as follows:

Bottles of 90 (NDC 42291-562-90)

Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container [see USP].

APOTEX INC.
MIDODRINE HYDROCHLORIDE TABLETS , USP 2.5 mg, 5 mg and 10 mg

Manufactured for: AvKARE, Inc. Pulaski, TN 38478 Mfg. Rev. (2) 02/17 AV 05/17 (P)