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 (Ref).
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 (Ref).
Hepatorenal syndrome type 1 or acute kidney injury, treatment (alternative agent) (off-label use):
Note: Alternative to norepinephrine or terlipressin (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
Postural orthostatic tachycardia syndrome (off-label use):
Oral: Initial: 2.5 mg 3 times daily (eg, morning, midday, and late afternoon); may increase gradually (eg, every 3 to 4 days) in increments of 2.5 mg/dose (eg, may increase from 2.5 mg 3 times daily to 5 mg 3 times daily) to a maximum of 10 mg 3 times daily. Avoid administering <4 hours before bedtime to minimize risk of supine hypertension (Ref).
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 (Ref).
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 (Ref).
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 (Ref). Although generally reported to be well-tolerated, midodrine-induced vascular ischemia has been reported in a dialysis patient with underlying peripheral vascular disease (Ref).
Altered kidney function:
eGFR ≥30 mL/minute/1.73m2: No dosage adjustment necessary (Ref).
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 (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (extent undetermined) (Ref): 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 (Ref). For use in the treatment of hemodialysis-induced hypotension, refer to adult dosing.
Peritoneal dialysis: Likely to be dialyzable (low protein binding) (Ref): 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 (Ref).
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 (Ref).
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 (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Refer to adult dosing.
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).
Risk factors:
• 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).
Risk factors:
• 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.
>10%:
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%) (table 1)
Drug (Midodrine) |
Placebo |
Number of Patients (Midodrine) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|
7% |
0% |
82 |
88 |
N/A |
13% |
N/A |
N/A |
N/A |
Increased systolic blood pressure (~200 mmHg) |
Dermatologic: Skin rash (2%)
Nervous system: Chills (5%), pain (5%; including abdominal pain)
<1%:
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
Gastrointestinal: Xerostomia
Nervous system: Abnormality in thinking, anxiety, confusion, headache, nervousness, sensation of pressure (intracranial)
Postmarketing:
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.
Disease-related concerns:
• 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.
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
Yes
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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 (indigo carm) 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 or acute kidney injury, treatment; Hypotension in the ICU, vasopressor sparing; Postural orthostatic tachycardia syndrome; Syncope, vasovagal
Midodrine may be confused with midostaurin, Midrin, minoxidil
ProAmatine may be confused with protamine
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha1-Blockers (Nonselective): May diminish the therapeutic effect of Midodrine. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Atropine (Systemic): May enhance the hypertensive effect of Alpha1-Agonists. Risk C: Monitor therapy
Benzylpenicilloyl Polylysine: Alpha1-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider delaying skin testing until alpha1-agonists are no longer required, or 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
Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy
Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. 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
Absorption: Rapid
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)
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