Midodrine Hydrochloride

2.5-mg, 5-mg and 10-mg tablets for oral administration. The 2.5-mg tablet is white, round, and biplanar, with a bevelled edge, and is scored on one side with “RPC” above and “2.5” below the score, and “003” on the other side. The 5-mg tablet is orange, round, and biplanar, with a bevelled edge, and is scored on one side with “RPC” above and “5” below the score, and “004” on the other side. The 10-mg is blue, round, and biplanar, with a bevelled edge, and is scored on one side with “RPC” above and “10” below the score, and “007” on the other side.

2.5-milligram Tablets (Bottle of 100): Shire US no longer markets this product

5.0-milligram Tablets (Bottle of 100): Shire US no longer markets this product

10-milligram Tablets (Bottle of 100): Shire US no longer markets this product

Store at 25°C (77°F)

Excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]

Shire US Inc., 300 Shire Way, Lexington, MA 02421, USA. Revised: Jan 2017

Symptoms of overdose could include hypertension, piloerection (goosebumps), a sensation of coldness and urinary retention. There are 2 reported cases of overdosage with ProAmatine®, both in young males. One patient ingested ProAmatine® 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 ProAmatine® (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 LD50 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).

Midodrine is a vasopressor. Midodrine causes constriction (tightening) of the blood vessels which leads to an increase in blood pressure.

Midodrine is used to treat low blood pressure.

Midodrine may also be used for purposes other than those listed here.

In some cases, midodrine may cause an excessive increase in blood pressure, especially when lying down. Contact your doctor immediately or seek emergency medical attention if you experience an unusual awareness of heartbeats, pounding in the ears, headache, or blurred vision. These may be signs of increased blood pressure.

In some cases, increased blood pressure may cause a slowed heart rate. Contact your doctor immediately or seek emergency medical attention if you experience decreased pulse rate, increased dizziness, fainting, or an unusual awareness of heartbeats. These may be signs of a slowed heart rate.

Midodrine can cause increased blood pressure when lying down. The last dose of midodrine should be taken at least 3 to 4 hours before bedtime. If you are going to be lying down for any length of time during the day, you may need to skip a dose of midodrine. Talk to your doctor about how to take midodrine if you lie down during the day.

Other prescription and over-the-counter medicines may cause an increase in blood pressure, which may be dangerous when taken with midodrine. Do not take any other prescription or over-the-counter medicines or herbal products especially cough, cold, or allergy products, weight loss products, asthma or respiratory medicines, migraine headache medicines, heart or blood pressure medicines, or antidepressants without first talking to your doctor.

A synthetic sympathomimetic amine structurally similar to methoxamine;2 9 a relatively long-acting α1-selective adrenergic agonist.1 3 4 5 6 7 8 9 11 12 13 14

Orthostatic Hypotension

Treatment of symptomatic orthostatic hypotension1 2 3 4 5 6 7 8 9 10 11 14 17 18 19 (designated an orphan drug by FDA for this use).15 Indication is based on effect on increases in 1-minute standing systolic BP, a surrogate marker; clinical benefits (principally improved ability to perform life activities) not established.22 Continue the drug only in patients who report substantial symptomatic improvement.22

Use recommended only in patients whose lives are considerably impaired despite standard clinical care; use only after nondrug therapies (e.g., support hose, increased sodium intake, life-style modifications) and fluid expansion have failed.1 11 12 18 20 May be more effective than comparative drugs (e.g., ephedrine) in managing postural symptoms.2 4

In August 2010, FDA proposed to withdraw approval of midodrine because required postapproval studies verifying the clinical benefit of the drug had not been done.23 24 25 FDA stated that neither the original manufacturer (Shire) nor any generic manufacturer had demonstrated clinical benefit (e.g., performance of life activities); data submitted had not verified expected clinical benefit.26 In September 2010, FDA clarified that its proposal was part of the regulatory process and that midodrine could remain on the market as that process moves forward.26 Subsequently, FDA and Shire reached an agreement that Shire would conduct 2 additional clinical studies to verify the clinical benefit of midodrine in patients with symptomatic orthostatic hypotension.28 29 In February 2012, FDA announced that the proposal to withdraw approval of midodrine will be deferred until these studies have been conducted; meanwhile, the drug remains approved and available on the US market.28 In September 2014, FDA extended the deadline to March 31, 2015 for final submission of study results and analyses for FDA review.30 31

• Midodrine is a prodrug; has little pharmacologic activity until metabolized to desglymidodrine.1 2 3 4 9 10 14 17 18

• Desglymidodrine is a relatively long-acting α1-selective adrenergic agonist1 3 4 5 6 7 8 9 11 12 13 14 that directly affects peripheral α-adrenergic receptors of the arterial and venous vasculature.1 2 3 4 5 6 9 11 12 13 17 18

• Increases SBP and DBP1 2 4 5 8 9 17 by increasing vascular tone,1 2 3 4 5 6 9 11 12 13 17 18 increasing total peripheral resistance,2 5 9 17 and possibly by expansion of extracellular fluid volume.4 7 12

• Has virtually no stimulant effect on β-adrenergic receptors, including those of the heart.1 2 3 4 5 6 11 13 Does not generally produce clinically important changes in pulse rates.1 5 Generally does not appear to produce appreciable CNS stimulation.1 2 3 5

• Efficacy may be related to autonomic function; patients with less severe autonomic dysfunction may benefit from midodrine therapy to a greater extent than those with severe autonomic dysfunction.7 12

• Risk of supine hypertension.1

• Importance of reporting promptly to their clinician symptoms of supine hypertension (e.g., cardiac awareness, pounding in the ears, headache, blurred vision).1

• Importance of administering last daily dose at least 4 hours before bedtime to reduce the occurrence of supine hypertension during sleep.1 14 16 18 Avoid taking a dose if patient will be supine for any length of time.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

• Importance of informing patients of other important precautionary information. (See Cautions.)