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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(MI doe dreen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Orphan drug: Treatment of symptomatic orthostatic hypotension
Use: Unlabeled
Management of urinary incontinence; vasovagal syncope; prevention of dialysis-induced hypotension
Pregnancy Risk Factor
C
Pregnancy Considerations
Increased rate of embryo resorption and decreased fetal weight were observed in animal studies. Use during pregnancy should be avoided unless the potential benefit outweighs the risk to the fetus.
Lactation
Excretion in breast milk is unknown/use caution
Contraindications
Hypersensitivity to midodrine or any component of the formulation; severe organic heart disease; acute renal failure; urinary retention; pheochromocytoma; thyrotoxicosis; persistent and significant supine hypertension
Warnings/Precautions
Boxed warnings:
• Appropriate use: See “Other warnings/precautions” below.
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).
• Hypertension: May cause hypertension.
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 and initiate with a reduced dose; contraindicated in patients with acute renal failure.
• Urinary retention: Use with caution in patients with urinary retention; reduce initial dose.
• Visual problems: Use with caution in patients with visual problems, especially if receiving fludrocortisone.
Other warnings/precautions:
• Appropriate use: [U.S. 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.
• Monitoring: Monitor renal and hepatic function prior to and periodically during therapy.
Adverse Reactions
>10%:
Cardiovascular: Supine hypertension (7% to 13%)
Dermatologic: Piloerection (13%), pruritus (12%)
Genitourinary: Urinary urgency, retention, or polyuria, dysuria (up to 13%)
Neuromuscular & skeletal: Paresthesia (18%)
1% to 10%:
Central nervous system: Chills (5%), pain (5%)
Dermatologic: Rash (2%)
Gastrointestinal: Abdominal pain
<1%: Anxiety, backache, canker sore, confusion, dizziness, dry skin, erythema multiforme, facial flushing, flatulence, flushing, GI distress, headache, heartburn, hyperesthesia, insomnia, ICP increased, leg cramps, nausea, somnolence, visual field defect, weakness, xerostomia
Metabolism/Transport Effects
None known.
Drug Interactions
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
Beta-Blockers: May enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cardiac Glycosides: May enhance the bradycardic effect of Midodrine. Risk C: 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. Risk X: Avoid combination
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
MAO Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification
Mechanism of Action
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.
Pharmacodynamics/Kinetics
Onset of action: ~1 hour
Duration: 2-3 hours
Absorption: Rapid
Distribution: Vd (desglymidodrine): <1.6 L/kg; poorly across membrane (eg, 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: ~3-4 hours; Midodrine: 25 minutes
Time to peak, serum: Desglymidodrine: 1-2 hours; Midodrine: 30 minutes
Excretion: Urine (Midodrine: Insignificant; Desglymidodrine: 80% by active renal secretion)
Dosage
Adults: Oral:
Orthostatic hypotension: 10 mg 3 times/day during daytime hours (every 3-4 hours) when patient is upright (maximum: 40 mg/day)
Prevention of hemodialysis-induced hypotension (unlabeled use): 2.5-10 mg given 15-30 minutes prior to dialysis session (Cruz, 1998; KDOQI, 2005; Prakash, 2004)
Vasovagal syncope (unlabeled use): Initial: 5 mg 3 times/day during daytime hours (every 6 hours) increased up to 15 mg/dose if necessary (Perez-Lugones, 2001; Ward, 1998)
Dosing adjustment in renal impairment: Orthostatic hypotension: 2.5 mg 3 times/day, gradually increasing as tolerated
Hemodialysis: Dialyzable; dose after hemodialysis unless used for prevention of hemodialysis-induced hypotension.
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. 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.
Monitoring Parameters
Blood pressure; renal and hepatic function
Patient Education
Take when sitting upright. Do not take within 4 hours of bedtime or when lying down for any length of time. Follow instructions for checking blood pressure and pulse routinely (same time of day; for 1 week at least). May cause urinary urgency or retention, dizziness, drowsiness, or headache. Report skin rash, severe gastric upset or pain, or muscle weakness or pain.
Geriatric Considerations
Adjust dosage for renal impairment.
Cardiovascular Considerations
Midodrine may increase blood pressure and should be carefully monitored in patients with underlying coronary artery disease. Midodrine may also worsen supine hypertension, a problem seen frequently in patients with diabetic autonomic neuropathy.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety, dizziness, confusion, or insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess for reduction of hypotension and adverse reactions (eg, supine hypertension, urinary urgency/retention, rash) prior to treatment and periodically thereafter. Standing blood pressure may be elevated 1 hour after administration and remain slightly elevated 3-4 hours.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as hydrochloride: 2.5 mg, 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Midodrine HCl)
5 mg (100): $199.99
10 mg (100): $291.01
References
Brignole M, Alboni P, Benditt DG, et al, “Guidelines on Management (Diagnosis and Treatment) of Syncope - Update 2004,” Europace, 2004, 6(6):467-537.
Cruz DN, Mahnensmith RL, Brickel HM, et al, “Midodrine is Effective and Safe Therapy for Intradialytic Hypotension Over 8 Months of Follow-up,” Clin Nephrol, 1998, 50(2):101-7.
Perez-Lugones A, Schweikert R, Pavia S, et al, “Usefulness of Midodrine in Patients With Severely Symptomatic Neurocardiogenic Syncope: A Randomized Control Study,” J Cardiovasc Electrophysiol, 2001, 12(8):935-8.
Prakash S, Garg AX, Heidenheim AP, et al, “Midodrine Appears to be Safe and Effective for Dialysis-Induced Hypotension: A Systematic Review,” Nephrol Dial Transplant, 2004, 19(10):2553-8.
Ward CR, Gray JC, Gilroy JJ, et al, “Midodrine: A Role in the Management of Neurocardiogenic Syncope,” Heart, 1998, 79(1):45-9.
National Kidney Foundation, “KDOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients,” Available at http://www.kidney.org/professionals/KDOQI/guidelines_cvd/index.htm
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
Content last modified January 2012
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