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.
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 2022a; 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 2 or 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]; Palma 2022).
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 with recurrent syncope despite nonpharmacologic measures. Regularly reassess dose (eg, every 3 to 6 months) and need for continued use (Benditt 2022; ESC [Brignole 2018).
Oral: Initial: 2.5 to 5 mg 3 times daily during daytime hours (eg, every 4 to 6 hours administered in morning, at noon, and late afternoon) when patient is upright; adjust dose and frequency as needed based on response and tolerability; usual dosage range: 2.5 mg twice daily 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; Sheldon 2021; Ward 1998).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Limited pharmacokinetic data available in kidney impairment. Desglymidodrine (active metabolite) is primarily renally eliminated and half-life is prolonged from 3 to 4 hours in patients with normal kidney function to 9 to 10 hours in patients with end-stage kidney disease (Blowey 1996; Rubinstein 2008). Although generally reported to be well-tolerated, midodrine-induced vascular ischemia has been reported in a dialysis patient with underlying peripheral vascular disease (Rubinstein 2008).
Altered kidney function:
eGFR ≥30 mL/minute/1.73m2: No dosage adjustment necessary (expert opinion).
eGFR <30 mL/minute/1.73m2: Initiate with a low dose (eg, 2.5 mg 1 to 3 times daily); increase to indication-specific dose as needed based on tolerability and response; use with caution (expert opinion; manufacturer's labeling).
Hemodialysis, intermittent (thrice weekly): Dialyzable (extent undetermined) (Blowey 1996): Initiate with a low dose (eg, 2.5 mg 1 to 2 times daily); increase to indication-specific dose as needed based on tolerability and response; use with caution (expert opinion). For use in the treatment of hemodialysis-induced hypotension, refer to adult dosing.
Peritoneal dialysis: Likely to be dialyzable (low protein binding) (expert opinion): Initiate with a low dose (eg, 2.5 mg 1 to 2 times daily); increase to indication-specific dose as needed based on tolerability and response; use with caution (expert opinion).
CRRT: Likely to be dialyzed: Initiate with doses on the lower end of the indication-specific recommended range and increase as needed based on tolerability and response; use with caution (expert opinion).
PIRRT: Likely to be dialyzed: Initiate with doses on the lower end of the indication-specific recommended range and increase as needed based on tolerability and response; use with caution (expert opinion).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Refer to adult dosing.
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
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Amatine: 10 mg [contains fd&c blue #2 aluminum lake]
Generic: 2.5 mg, 5 mg
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.
Hypotension, symptomatic orthostatic: Treatment of symptomatic orthostatic hypotension.
Ascites, cirrhotic, diuretic resistant or with hypotension; Hemodialysis-induced hypotension, prevention; Hepatorenal syndrome (type 1); Hypotension in the ICU, vasopressor sparing; Postural tachycardia syndrome; Syncope, vasovagal
Midodrine may be confused with midostaurin, Midrin, minoxidil
ProAmatine may be confused with protamine
Midodrine may cause bradycardia primarily due to vagal reflex (Ref).
Mechanism: Dose-related; related to the vasoconstrictive pharmacologic action; thought to be due to activation of the baroreceptor reflex (Ref).
• Higher doses (Ref)
• Concurrent medications with negative chronotropic effects (eg, beta-blockers, digoxin) (Ref)
• Kidney impairment (Ref)
• Sick sinus syndrome (Ref)
Midodrine may cause supine hypertension. Supine increases of 16 to 18 mm Hg have been reported (Ref).
Mechanism: Dose-related; related to the vasoconstrictive pharmacologic action. Increases blood pressure and vascular tone by stimulating arterial and venous alpha receptors (Ref).
• Higher doses (Ref)
• Supine position (Ref)
• Baseline blood pressure elevations (Ref)
• Concurrent use of vasoconstrictors (eg, phenylephrine, ephedrine, dihydroergotamine, phenylpropanolamine, pseudoephedrine)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Dermatologic: Piloerection (13%), pruritus (12%; mainly of the scalp)
Genitourinary: Dysuria (13%; including urinary frequency, urinary retention, urinary urgency)
Nervous system: Paresthesia (18%)
1% to 10%:
Cardiovascular: Supine hypertension (7%; increased systolic blood pressure [~200 mmHg]: 13%)
Number of Patients (Midodrine)
Number of Patients (Placebo)
Increased systolic blood pressure (~200 mmHg)
Dermatologic: Skin rash (2%)
Nervous system: Chills (5%), pain (5%; including abdominal pain)
Dermatologic: Erythema multiforme, xeroderma
Gastrointestinal: Aphthous stomatitis, flatulence, gastrointestinal distress, heartburn, nausea
Nervous system: Dizziness, drowsiness, hyperesthesia (skin), insomnia
Neuromuscular & skeletal: Asthenia, back pain, lower limb cramp
Ophthalmic: Visual field defect
Frequency not defined:
Cardiovascular: Facial flushing, vasodilation
Nervous system: Abnormality in thinking, anxiety, confusion, headache, nervousness, sensation of pressure (intracranial)
Cardiovascular: Bradycardia (Cordeiro 2019), vascular disease (Rubenstein 2008)
Dermatologic: Acute generalized exanthematous pustulosis (Sadeghpour 2014)
Gastrointestinal: Dysgeusia (Horger 2016)
Nervous system: Altered sense of smell (Horger 2016), myoclonus (Ye 2020)
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.
• Diabetes: Use with caution in patients with diabetes mellitus.
• Hepatic impairment: Use with caution in patients with hepatic impairment; midodrine is a prodrug metabolized to an active metabolite (desglymidodrine).
• 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.
Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: 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. Risk D: Consider therapy modification
Bradycardia-Causing Agents: Midodrine may enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Bromocriptine: May enhance the hypertensive effect of Alpha1-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider therapy modification
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: 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. Risk D: Consider therapy modification
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy
Droxidopa: Midodrine may enhance the hypertensive effect of Droxidopa. Risk C: Monitor therapy
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May enhance the vasoconstricting effect of Alpha1-Agonists. Risk X: Avoid combination
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: 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. Risk X: Avoid combination
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: 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. Risk D: Consider therapy modification
Lisuride: May enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination
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. Risk X: Avoid combination
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Pergolide: May enhance the hypertensive effect of Alpha1-Agonists. Risk C: Monitor therapy
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the therapeutic effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the therapeutic effect of Alpha1-Agonists. Risk C: Monitor therapy
Adverse events were observed in animal reproduction studies. Information related to the use of midodrine in pregnancy is limited (Glatter 2005).
It is not known if midodrine is excreted in breast milk. The manufacturer recommends that caution be exercised when administering midodrine to nursing women.
BP while supine, sitting, and standing upon awakening; signs or symptoms of bradycardia; renal and hepatic function.
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.
Onset of action: ~1 hour
Duration: 2 to 3 hours
Distribution: Poorly crosses blood-brain barrier
Protein binding: Minimal
Metabolism: Hepatic and many other tissues; midodrine is a prodrug which undergoes rapid deglycination to desglymidodrine (active metabolite)
Bioavailability: Desglymidodrine: 93%
Half-life elimination: Desglymidodrine: ~3 to 4 hours; Midodrine: 25 minutes
Time to peak, serum: Desglymidodrine: 1 to 2 hours; Midodrine: 30 minutes
Excretion: Urine (Midodrine: Insignificant; Desglymidodrine: 80% by active renal secretion)
Tablets (Midodrine HCl Oral)
2.5 mg (per each): $1.03 - $1.69
5 mg (per each): $1.04 - $4.49
10 mg (per each): $4.84 - $9.72
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