Skip to Content

Midodrine

Medically reviewed by Drugs.com. Last updated on Jun 27, 2020.

Pronunciation

(MI doe dreen)

Index Terms

  • Midodrine HCl
  • Midodrine Hydrochloride
  • ProAmatine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Generic: 2.5 mg, 5 mg, 10 mg

Pharmacologic Category

  • Alpha1 Agonist

Pharmacology

Midodrine forms an active metabolite, desglymidodrine, which 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.

Absorption

Rapid

Distribution

Poorly crosses blood-brain barrier

Metabolism

Hepatic and many other tissues; midodrine is a prodrug which undergoes rapid deglycination to desglymidodrine (active metabolite)

Excretion

Urine (Midodrine: Insignificant; Desglymidodrine: 80% by active renal secretion)

Onset of Action

~1 hour

Time to Peak

Desglymidodrine: 1 to 2 hours; Midodrine: 30 minutes

Duration of Action

2 to 3 hours

Half-Life Elimination

Desglymidodrine: ~3 to 4 hours; Midodrine: 25 minutes

Protein Binding

Minimal

Use: Labeled Indications

Hypotension, symptomatic orthostatic: Treatment of symptomatic orthostatic hypotension.

Off Label Uses

Ascites, cirrhotic, diuretic resistant or with hypotension

Data from a limited number of patients studied suggest that midodrine may be beneficial for the treatment of diuretic-resistant cirrhosis-induced ascites [Singh 2012], [Yosry 2019].

Based on American Association for the Study of Liver Diseases (AASLD) clinical practice guidelines for the management of adult patients with ascites due to cirrhosis, midodrine, in addition to diuretics, should be considered for the management of refractory ascites, especially in hypotensive patients [AASLD [Runyon 2013]].

Hemodialysis-induced hypotension, prevention

Data from several small studies have demonstrated hemodynamic improvements (eg, systolic and diastolic BP) with midodrine in patients who experience hemodialysis-induced hypotension [Cruz 1997], [Cruz 1998], [Flynn 1996], [Prakash 2004].

Based on the Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for cardiovascular disease in dialysis patients, midodrine is effective and recommended in the prevention of or the amelioration of the symptoms and severity of dialysis-induced hypotension (also known as intradialytic hypotension) [KDOQI 2005].

Hepatorenal syndrome (type 1)

Data from a small controlled trial in patients with type 1 hepatorenal syndrome treated with midodrine, octreotide, and albumin showed significant improvement in renal plasma flow, glomerular filtration rate, and urinary sodium excretion [Angeli 1999]. Retrospective data also suggest improvement in 30-day mortality with the combination of midodrine, octreotide, and albumin [Esrailian 2007], [Skagen 2009].

Based on AASLD clinical practice guidelines for the management of adult patients with ascites due to cirrhosis, midodrine in combination with octreotide and albumin should be considered for the treatment of type 1 hepatorenal syndrome [AASLD [Runyon 2013]].

Hypotension in the ICU, vasopressor sparing

Data from one small, prospective, observational study and several retrospective, single-center, observational studies suggest that the use of midodrine as adjunctive therapy to IV vasopressors in stable patients in the ICU may be beneficial to decrease the duration of IV vasopressor use and shorten length of ICU stay [Levine 2013], [Poveromo 2016], [Rizvi 2018], [Whitson 2016].

Postural tachycardia syndrome

Data from a limited number of patients studied suggest that midodrine may be beneficial for the treatment of postural tachycardia syndrome [Gordon 2000], [Jacob 1997].

Syncope, vasovagal

Data from 2 randomized, double-blind, placebo-controlled studies in a limited number of patients with frequent syncopal episodes who were not initially treated with nonpharmacologic therapy (eg, adequate fluid and salt intake, regular exercise, physical counterpressure maneuvers) suggest that the use of midodrine may be beneficial in the treatment of vasovagal syncope [Perez-Lugones 2001], [Ward 1998].

Based on the 2018 European Society of Cardiology guidelines for the diagnosis and management of syncope, use of midodrine may be considered for treatment of patients with the orthostatic form of vasovagal syncope [ESC [Brignole 2018]].

Based on the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines for the evaluation and management of patients with syncope, midodrine may be used for treatment in patients with recurrent vasovagal syncope with no history of hypertension, heart failure, or urinary retention [ACC/AHA/HRS [Shen 2017]].

Contraindications

Severe organic heart disease; acute renal disease; urinary retention; pheochromocytoma; thyrotoxicosis; supine hypertension; poorly controlled hypertension.

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to midodrine or any component of the formulation; obliterative or spastic vessel disease; renal insufficiency; hypertrophy of prostate gland with formation of residual urine; hyperthyroidism; narrow angle glaucoma.

Dosing: Adult

Ascites, cirrhotic, diuretic resistant or with hypotension (off-label use):

Oral: Initial: 5 to 7.5 mg 3 times daily; adjust dose in increments of 2.5 mg per dose (eg, increase from 5 mg 3 times daily to 7.5 mg 3 times daily) every 24 hours to achieve target mean arterial pressure; maximum dose: 17.5 mg 3 times daily (AASLD [Runyon 2013]; Runyon 2020a; Singh 2012; Skagen 2009; Yosry 2019).

Hemodialysis-induced hypotension, prevention (off-label use):

Note: Used in conjunction with other therapy adjustments for preventing recurrent intradialytic hypotension.

Oral: Initial: 2.5 to 5 mg given 15 to 30 minutes prior to hemodialysis. If response is insufficient, may increase up to 10 mg given 15 to 30 minutes prior to the next hemodialysis session; if hypotension occurs near the end of hemodialysis, may give an additional 2.5 to 5 mg dose mid-dialysis provided it is administered ≥3 hours after pre-dialysis dose (Cruz 1997; Cruz 1998; Flynn 1996; Henrich 2020; KDOQI 2005; Prakash 2004).

Hepatorenal syndrome (type 1) (alternative agent) (off-label use):

Note: Alternative to terlipressin (not available in the US or Canada) for patients not admitted to the ICU.

Oral: Initial: 5 to 10 mg 3 times daily in combination with albumin and octreotide; adjust dose (eg, by 2.5 to 5 mg per dose) as needed after each 8-hour dosing interval, with an immediate goal of increasing mean arterial pressure by ~10 to 15 mm Hg; maximum dose: 15 mg 3 times daily (AASLD [Runyon 2013]; Angeli 1999; Esrailian 2007; Garcia-Tsao 2009; Runyon 2020b).

Hypotension in the ICU, vasopressor sparing (off-label use):

Note: According to some experts, may be useful to facilitate discontinuation of low-dose IV vasopressors; prospective data are limited. Reevaluate therapy regularly, including at each transition of care (Buckley 2019; Rizvi 2018).

Oral: Initial: 5 to 10 mg every 8 hours; titrate based on response and tolerability; usual dose: 10 to 20 mg every 8 hours; maximum reported dose: 40 mg every 8 hours. When hemodynamically stable, taper and discontinue (Buckley 2019; Hammond 2019; Levine 2013; Poveromo 2016; Rizvi 2018; Whitson 2016).

Hypotension, symptomatic orthostatic:

Note: Individual doses >10 mg and total daily doses >30 mg can cause severe supine hypertension and bradycardia. Adjust dose or discontinue if supine BP increases excessively.

Oral: Initial: 2.5 mg 3 times daily during daytime hours (eg, every 3 to 4 hours) when patient is upright; titrate as needed based on response and tolerability up to a usual maximum dose of 10 mg 3 times daily. Avoid administering <4 hours before bedtime to minimize risk of supine hypertension (ESC [Brignole 2018]; Kaufmann 2020).

Postural tachycardia syndrome (off-label use):

Oral: Usual dosage range: 2.5 to 10 mg 3 times daily when patient is upright. Slow upward titration with BP monitoring is advised. Avoid administering <4 hours before bedtime to minimize risk of supine hypertension (Gordon 2000; Jacob 1997; Kaufmann 2020).

Syncope, vasovagal (off-label use):

Note: Consider for use in patients refractory to nonpharmacologic measures; regularly reassess dose (eg, every 3 to 6 months) and need for continued use (Benditt 2020; ESC [Brignole 2018).

Oral: Initial: 2.5 to 5 mg 3 times daily during daytime hours (eg, every 6 hours administered in morning, at noon, and late afternoon) when patient is upright; gradually increase dose as needed based on response and tolerability up to 10 mg 3 times daily; maximum reported dose: 15 mg 3 times daily. Avoid administering <4 hours before bedtime to minimize risk of supine hypertension (ESC [Brignole 2018]; Perez-Lugones 2001; Ward 1998).

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: 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 to prevent supine hypertension.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from light and moisture.

Drug Interactions

Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Benzylpenicilloyl Polylysine: Alpha1-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Consider therapy modification

Bradycardia-Causing Agents: Midodrine may enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Droxidopa: Midodrine may enhance the hypertensive effect of Droxidopa. Monitor therapy

Ergot Derivatives: May enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Iobenguane Radiopharmaceutical Products: Alpha1-Agonists may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Avoid combination

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Exceptions: Linezolid. Avoid combination

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Consider therapy modification

Procarbazine: May enhance the adverse/toxic effect of Sympathomimetics. Management: Consider alternatives to this combination when possible. Procarbazine prescribing information states that this combination should be avoided. Consider therapy modification

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tricyclic Antidepressants: May enhance the therapeutic effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the therapeutic effect of Alpha1-Agonists. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Supine hypertension (7% to 13%)

Central nervous system: Paresthesia (18%)

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

Genitourinary: Dysuria (≤13%), urinary retention, urinary urgency

Renal: Polyuria

1% to 10%:

Central nervous system: Chills (5%), pain (5%)

Dermatologic: Skin rash (2%)

Gastrointestinal: Abdominal pain

<1%, postmarketing, and/or case reports: Anxiety, aphthous stomatitis, back pain, confusion, dizziness, drowsiness, erythema multiforme, facial flushing, flatulence, flushing, gastrointestinal distress, headache, heartburn, hyperesthesia, increased intracranial pressure, insomnia, leg cramps, nausea, visual field defect, weakness, xeroderma, xerostomia

ALERT: U.S. Boxed Warning

Appropriate use:

Because midodrine can cause marked elevation of supine blood pressure, it should be used in patients whose lives are considerably impaired despite standard clinical care. The indication for use of midodrine in the treatment of symptomatic orthostatic hypotension is based primarily on a change in a surrogate marker of effectiveness, an increase in systolic blood pressure measured 1 minute after standing, a surrogate marker considered likely to correspond to a clinical benefit. At present, however, clinical benefits of midodrine, principally improved ability to carry out activities of daily living, have not been verified.

Warnings/Precautions

Concerns related to adverse effects:

• Bradycardia: May slow heart rate primarily due to vagal reflex. Use caution when administered concurrently with negative chronotropes (eg, digoxin, beta blockers). Discontinue use if signs or symptoms of bradycardia occur.

• Hypertension: May cause supine hypertension; discontinue use immediately if supine hypertension persists. Use with caution when administered concurrently with vasoconstrictors (eg, phenylephrine, ephedrine, dihydroergotamine, phenylpropanolamine, pseudoephedrine). Use is not recommended in patients with initial supine systolic pressure >180 mm Hg. Due to marked elevation of supine blood pressure (BP >200 mm Hg systolic), use in patients whose lives are considerably impaired despite standard clinical care, including nonpharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations. Supine and sitting blood pressure should be monitored.

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes mellitus.

• Hepatic impairment: Use with caution in patients with hepatic impairment; has not been studied.

• Renal impairment: Desglymidodrine, the active metabolite, is primarily renally excreted; assess renal function prior to initial dose; use with caution in patients with renal impairment (has not been studied) and initiate with a reduced dose; contraindicated in patients with acute renal failure.

• Visual problems: Use with caution in patients with visual problems, especially if receiving fludrocortisone.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Indicated for patients for whom orthostatic hypotension significantly impairs their daily life despite standard clinical care. Use is not recommended with supine hypertension. Continue therapy only in patients who appear to attain symptomatic improvement during initial treatment.

Monitoring Parameters

Blood pressure while supine, sitting, and standing upon awakening; renal and hepatic function.

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Information related to the use of midodrine in pregnancy is limited (Glatter 2005).

Patient Education

What is this drug used for?

• It is used to treat low blood pressure.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Scalp tingling

• Itching

• Goose bumps

• Chills

• Passing a lot of urine

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Severe dizziness

• Passing out

• Severe headache

• Vision changes

• Slow heartbeat

• Pounding in the ears

• Trouble urinating

• Burning or numbness feeling

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.