No

Alpha₁ Agonist

Treatment of symptomatic orthostatic hypotension

C

Clinical effects on the fetus: No studies are available; use during pregnancy and lactation should be avoided unless the potential benefit outweighs the risk to the fetus

Severe organic heart disease, urinary retention, pheochromocytoma, thyrotoxicosis, persistent and significant supine hypertension; hypersensitivity to midodrine or any component; concurrent use of fludrocortisone

Only indicated for patients for whom orthostatic hypotension significantly impairs their daily life. Use is not recommended with supine hypertension and caution should be exercised in patients with diabetes, visual problems, urinary retention (reduce initial dose) or hepatic dysfunction; monitor renal and hepatic function prior to and periodically during therapy; safety and efficacy has not been established in children; discontinue and re-evaluate therapy if signs of bradycardia occur.

>10%:

Dermatologic: Piloerection (13%), pruritus (12%)

Genitourinary: Urinary urgency, retention, or polyuria, dysuria (up to 13%)

Neuromuscular & skeletal: Paresthesia (18.3%)

1% to 10%:

Cardiovascular: Supine hypertension, (7%) facial flushing

Central nervous system: Confusion, anxiety, dizziness, chills (5%)

Dermatologic: Rash, dry skin (2%)

Gastrointestinal: Xerostomia, nausea, abdominal pain

Neuromuscular & skeletal: Pain (5%)

<1%: Flushing, headache, insomnia, flatulence, leg cramps, visual changes

Symptoms of overdose include hypertension, piloerection, urinary retention

Treatment is symptomatic following gastric decontamination; alpha-sympatholytics and/or dialysis may be helpful

Increased effect: Concomitant fludrocortisone results in hypernatremia or an increase in intraocular pressure and glaucoma; bradycardia may be accentuated with concomitant administration of cardiac glycosides, psychotherapeutics, and beta-blockers; alpha-agonists may increase the pressure effects and alpha-antagonists may negate the effects of midodrine

Midodrine forms an active metabolite, desglymidodrine, that is an alpha₁-agonist. This agent increases arteriolar and venous tone resulting in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension.

Pure autonomic failure (Bradbury-Eglleston syndrome, idiopathic orthostatic hypotension)

Autonomic failure with multiple system atrophy (Shy-Drager syndrome)

Familial dysautonomia (Riley-Day syndrome)

Dopamine beta-hydroxylase deficiency

Secondary Autonomic Causes of Orthostatic Hypotension:

Chronic alcoholism

Parkinson's disease

Diabetes mellitus

Porphyria

Amyloidosis

Various carcinomas

Vitamin B₁ or B₁₂ deficiency

Nonautonomic Causes of Orthostatic Hypotension:

Hypovolemia (such as associated with hemorrhage, burns, or hemodialysis) and dehydration

Diminished homeostatic regulation (such as associated with aging, pregnancy, fever, or prolonged best rest)

Medications (eg, antihypertensives, insulin, tricyclic antidepressants)

Onset of action: Within 1 hour

Duration: May last for 2-3 hours

Absorption: Rapid

Distribution: V_d (desglymidodrine): <1.6 L/kg; poorly distributed across membrane (eg, blood brain barrier)

Protein binding: Minimal

Metabolism: Rapid deglycination to desglymidodrine occurs in many tissues and plasma; further metabolism in the liver

Bioavailability: Absolute, 93%

Half-life: ~3-4 hours (active drug); 25 minutes (prodrug)

Time to peak serum concentration: 1-2 hours (active drug); 30 minutes (prodrug)

Elimination: Renal, minimal (2% to 4%); clearance of desglymidodrine: 385 mL/minute (predominantly by renal secretion)

Adults: Oral: 10 mg 3 times/day during daytime hours (every 3-4 hours) when patient is upright (maximum: 40 mg/day)

Blood pressure, renal and hepatic parameters

May cause anxiety, dizziness, confusion, or insomnia

None reported

No information available to require special precautions

1% to 10% of patients experience significant dry mouth

This drug may relieve positional hypotension; effects must be evaluated regularly. Take prescribed amount 3 times daily (shortly before rising in the morning, at midday, and in late afternoon); do not take after 6 PM or within 4 hours of bedtime or when lying down for any length of time. Follow recommended diet and exercise program. Do not use OTC medications which may affect blood pressure (eg, cough or cold remedies, diet pills, stay-awake medications) without consulting prescriber. You may experience urinary urgency or retention (void before taking or consult prescriber if difficulty persists); or dizziness, drowsiness, or headache (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report skin rash, severe gastric upset or pain, muscle weakness or pain, or other persistent side effects. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Doses may be given in approximately 3- to 4-hour intervals (eg, shortly before or upon rising in the morning, at midday, in the late afternoon not later than 6 PM); avoid dosing after the evening meal or within 4 hours of bedtime; continue therapy only in patients who appear to attain symptomatic improvement during initial treatment; standing systolic blood pressure may be elevated 15-30 mm Hg at 1 hour after a 10 mg dose; some effect may persist for 2-3 hours

Tablet, as hydrochloride: 2.5 mg, 5 mg