Midodrine | Medication Reference

Bedside Snapshot

Drug Class: Oral α₁-adrenergic agonist (via active metabolite); antihypotensive agent
Mechanism: Oral prodrug; active metabolite (desglymidodrine) is a selective peripheral α₁-agonist → arteriolar and venous vasoconstriction → increased systemic vascular resistance and increased standing blood pressure with minimal CNS penetration
Primary Approved Use: Symptomatic neurogenic orthostatic hypotension (nOH) due to autonomic failure (e.g., multiple system atrophy, Parkinson disease, pure autonomic failure)
Off-Label Uses: Intradialytic hypotension, hypotension limiting heart-failure guideline-directed therapy, adjunct in ICU vasopressor weaning (evidence mixed/weak)
Typical Adult Orthostatic Hypotension Dosing: Start 2.5 mg PO three times daily; increase weekly based on response and supine/standing BP up to 10 mg three times daily (max 30 mg/day)
Critical Timing: Last dose should be taken at least 4 hours before bedtime to reduce risk of supine hypertension
Onset: Active metabolite peaks ~1 hour after a dose; clinical effect begins within about 30–60 minutes, with duration roughly 3–4 hours (range ~2–6 hours)
Major Risk: Supine hypertension—patients should avoid dosing close to bedtime and should not take doses when they expect to be lying flat for longer periods
Key Contraindications: Severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma, thyrotoxicosis, and persistent/excessive supine hypertension
Common Side Effects: Piloerection ("gooseflesh"), scalp paresthesias/itching, urinary urgency/retention, chills, pruritus, mild hypertension
Serious Risks: Marked supine hypertension, bradycardia, ischemia in susceptible patients

Brand & Generic Names

Generic Name: Midodrine hydrochloride
Brand Names: ProAmatine, Amatine, Gutron, plus multiple generics; availability is region- and institution-specific

Medication Class

Oral α₁-adrenergic agonist (via active metabolite); antihypotensive agent

Pharmacology

Mechanism of Action:

Midodrine is a prodrug that is rapidly deglycinated to its active metabolite, desglymidodrine
Desglymidodrine is a selective α₁-adrenergic receptor agonist acting on arteriolar and venous smooth muscle → increased peripheral vascular resistance and venous return, elevating standing and sitting blood pressure
Because midodrine/desglymidodrine poorly cross the blood–brain barrier, they primarily exert peripheral effects and are not strongly associated with CNS stimulation or insomnia
In neurogenic orthostatic hypotension, autonomic vasoconstrictor responses are blunted; midodrine restores some of this peripheral vasoconstriction, improving standing BP and reducing symptoms such as lightheadedness, syncope, and fatigue
Unlike catecholamine infusions, midodrine is not directly inotropic or chronotropic at therapeutic doses, although reflex changes in heart rate may occur in response to BP changes

Pharmacokinetics (Oral):

Route: Oral tablets (and capsules in some markets) are the only routine systemic formulation; there is no standard IV formulation for routine clinical use
Absorption: Rapidly absorbed after oral administration; parent midodrine peaks in plasma ~0.5 hours after dosing
Metabolism: Midodrine is converted (deglycination) to the active metabolite, desglymidodrine, in multiple tissues; neither midodrine nor desglymidodrine is a substrate for monoamine oxidase
Desglymidodrine pharmacokinetics: Peak plasma concentration typically at 1–2 hours; elimination half-life ~3–4 hours; clinical duration of effect is generally 3–4 hours (often quoted range 2–6 hours)
Bioavailability: The absolute bioavailability of midodrine measured as desglymidodrine is high (~90%+); food may slightly delay absorption but does not meaningfully reduce exposure for most patients
Elimination: Primarily renal excretion of desglymidodrine and metabolites; in renal impairment, both Cmax and half-life are increased, requiring dose reduction and close monitoring
Dosing frequency: Because of its relatively short half-life, midodrine is typically dosed three times daily during waking hours, with the last dose at least 4 hours before bedtime to limit supine hypertension

Indications

Symptomatic neurogenic orthostatic hypotension due to autonomic failure (e.g., multiple system atrophy, Parkinson disease with autonomic failure, pure autonomic failure) when non-pharmacologic measures are insufficient
Orthostatic hypotension related to spinal cord injury or other autonomic neuropathies (e.g., diabetic autonomic neuropathy) under specialist supervision
Off-label: Prevention or treatment of intradialytic hypotension in hemodialysis patients (typically 2.5–10 mg PO before dialysis)
Off-label: Adjunctive therapy for chronic symptomatic hypotension limiting optimization of heart-failure guideline-directed medical therapy (GDMT) in selected patients
Off-label (ICU): Adjunct for weaning from intravenous vasopressors in vasodilatory or distributive shock; evidence from RCTs and observational studies is mixed and does not consistently show reduced vasopressor duration or ICU length of stay

Dosing & Administration

Available Forms:

Oral tablets: Commonly 2.5 mg, 5 mg, and 10 mg strengths
Some markets also have capsules in similar strengths; verify available formulations in your formulary
No standard IV formulation is approved for routine clinical use; midodrine is intended as an oral agent
Tablets may be taken with or without food and swallowed with water
Should be dosed during waking hours with attention to supine blood pressure

Standard Dosing – Oral Midodrine (Always Follow Local Protocols and Autonomic/Renal/Cardiology Guidance):

Indication / Population	Initial Dose	Titration	Typical Maximum
Adult neurogenic orthostatic hypotension (nOH)	2.5 mg PO three times daily during waking hours	Increase by 2.5 mg per dose every ≥1 week based on symptoms and supine/standing BP; usual effective dose 5–10 mg TID	10 mg three times daily (30 mg/day) in most product labels/guidelines
Elderly / frail / moderate CKD	2.5 mg PO two or three times daily	Up-titrate cautiously (e.g., to 5 mg TID) with frequent supine/standing BP checks and renal function monitoring	Often limited to 5–7.5 mg TID depending on tolerance and BP
Intradialytic hypotension (off-label)	2.5–10 mg PO about 30 minutes before hemodialysis	Adjust dose session-to-session according to intradialytic BP and symptoms	Commonly ≤10 mg pre-dialysis; higher chronic doses require specialist oversight
ICU vasopressor-weaning (off-label, investigational)	5–10 mg PO three times daily, started once vasopressor dose is low and stable	Some studies used 10 mg TID; adjust to BP and clinical response, and stop if supine hypertension or bradycardia occurs	Common study max 10–20 mg TID; routine use requires local protocol and intensivist oversight

Critical Timing to Prevent Supine Hypertension: Last daily dose should be taken at least 4 hours before bedtime to reduce risk of supine hypertension. Avoid dosing if the patient plans to lie down for a prolonged period. Patients should measure or have measured both supine and standing blood pressures during titration.

Additional Dosing Notes:

Therapy should be held or reduced if supine systolic BP is persistently very high (e.g., ≥180 mmHg) or if troublesome symptoms of hypertension occur
In CKD (e.g., eGFR <60 mL/min/1.73 m²), consider lower starting doses (2.5 mg BID–TID) and slower titration with close monitoring; avoid use in acute renal failure unless specifically directed by nephrology
If midodrine is being used off-label (dialysis hypotension, HF, ICU weaning), there should be an explicit plan for reassessment and discontinuation if clear benefit is not seen or once the precipitating issue resolves
Dose adjustments should be individualized based on symptoms, orthostatic BP response, and adverse effects rather than chasing a specific "target" dose

Contraindications

Labeled/Major Contraindications:

Persistent and excessive supine hypertension
Severe organic heart disease (e.g., significant ischemic heart disease, advanced congestive heart failure, serious conduction disturbances)
Acute renal disease or severe renal impairment without specialist guidance
Urinary retention or significant urinary outflow obstruction (e.g., severe BPH)
Pheochromocytoma or other catecholamine-secreting tumors
Thyrotoxicosis
Known hypersensitivity to midodrine or excipients

Major Precautions:

Baseline supine hypertension: Midodrine may further increase supine BP; weigh risks vs. benefits and ensure head-of-bed elevation and timing adjustments
Chronic kidney disease: Reduced clearance increases exposure; start at low doses with careful titration and more frequent BP and renal function monitoring
Benign prostatic hyperplasia or other lower urinary tract obstruction: Midodrine can increase bladder neck tone and precipitate urinary retention
Diabetes with autonomic neuropathy: Higher baseline risk for supine hypertension and autonomic instability; monitoring and dose titration should be especially cautious
Concurrent use with other vasopressors or α-agonists: (e.g., during ICU weaning) increases risk of excessive hypertension and ischemia; ensure clear goals and close hemodynamic monitoring
Pregnancy: Limited data; generally avoided unless potential benefit outweighs risk and other options are unsuitable; involve obstetrics and maternal–fetal medicine as needed

Adverse Effects

Common (often dose-related):

Piloerection ("goosebumps"), chills, and a sense of cold extremities
Scalp and skin paresthesias or pruritus (especially of the head and neck)
Supine or sitting hypertension, including headache, pounding in the ears, and blurred vision
Urinary urgency or frequency; mild urinary retention in predisposed patients
GI upset (nausea, dyspepsia) and dry mouth

Serious:

Marked supine hypertension: Risk of stroke, myocardial infarction, or acute heart failure
Symptomatic bradycardia or reflex slowing of heart rate: Particularly when combined with β-blockers or other negative chronotropes
Precipitation or worsening of ischemic heart disease or heart failure: In susceptible patients due to increased afterload
Urinary retention: Requiring catheterization or urologic intervention, particularly in patients with BPH or neurogenic bladder
Rare allergic reactions: Rash, urticaria

Special Populations

Renal impairment: In CKD (eGFR <60 mL/min/1.73 m²), start with lower doses (2.5 mg BID or TID) and titrate slowly with close BP and renal function monitoring; avoid in acute renal failure without specialist guidance
Hepatic impairment: No specific dose adjustment recommended in product labeling, but use with caution and monitor closely
Older adults: Start at lower doses (2.5 mg BID or TID) with slower titration; higher risk for supine hypertension, urinary retention (especially with BPH), and orthostatic instability
Pregnancy: Limited data; generally avoided; use only if potential benefit clearly outweighs risk; no well-controlled studies in pregnant women
Lactation: Unknown if excreted in breast milk; use caution and consider risk-benefit
Pediatrics: Safety and efficacy not established in pediatric populations; use only under specialist guidance if alternative treatments are unsuitable

Monitoring

Supine and standing (or sitting/standing) blood pressure and heart rate: At baseline and during dose titration; ideally check supine at bedtime and on waking, and standing after 1–3 minutes
Symptoms of orthostatic intolerance: Dizziness, presyncope/syncope, fatigue compared with baseline to assess benefit
Symptoms/signs of supine hypertension: Headache, pounding in ears, blurred vision, chest discomfort, and new or worsening angina or dyspnea
Renal function: Serum creatinine, eGFR at baseline and periodically during therapy, especially in CKD or when combined with nephrotoxic drugs
Urinary symptoms: Frequency, hesitancy, incomplete emptying, and post-void residuals in at-risk patients (e.g., BPH, neurogenic bladder)

Clinical Pearls

Timing is everything: Encourage patients to take midodrine shortly before upright activity (e.g., breakfast, lunch, mid-afternoon) and avoid dosing within at least 4 hours of going to bed. This simple timing adjustment is the most effective way to prevent nocturnal supine hypertension.

Head-of-bed elevation strategy: Head-of-bed elevation at night (e.g., 10–20°) and avoidance of late-evening doses can meaningfully reduce nocturnal supine hypertension risk while maintaining daytime benefit.

Optimize non-pharmacologic measures first: In neurogenic orthostatic hypotension, non-pharmacologic measures (compression garments, fluid/salt loading, physical counter-maneuvers) should be optimized before and alongside midodrine; this often improves efficacy and allows lower doses.

Intradialytic hypotension timing: For intradialytic hypotension, giving midodrine 20–30 minutes before dialysis is a common strategy; still, volume status and dialysis prescription (UF rate, dialysate temperature, sodium profile) remain fundamental.

ICU vasopressor weaning evidence is mixed: Evidence for using midodrine to wean IV vasopressors is mixed; some small trials show no significant reduction in vasopressor duration. Its use in the ICU should be protocolized and reserved for carefully selected patients.

Supine hypertension management: If supine hypertension becomes problematic despite dose timing and head-of-bed elevation, reducing the dose or discontinuing midodrine is usually preferred over adding more antihypertensives, which can worsen orthostatic symptoms.

Periodic reassessment: Reassess the ongoing need for midodrine periodically—particularly after recovery from acute illness, medication changes (e.g., diuretic reduction), or improvement in autonomic function. Many patients are maintained on midodrine indefinitely without re-evaluation.

Characteristic side effects are benign: Piloerection ("goosebumps") and scalp tingling are characteristic midodrine side effects and are usually benign, though they can be bothersome. Patients should be counseled that these effects typically diminish with continued use and are not dangerous.

References

1. DrugBank Online. (2024). Midodrine (DB00211). DrugBank. https://go.drugbank.com/drugs/DB00211
2. Fedorowski, A. (2022). Orthostatic hypotension: Management of a complex, but common cardiovascular disorder. Circulation: Arrhythmia and Electrophysiology, 15(3), e010573. https://doi.org/10.1161/CIRCEP.121.010573
3. Kaufmann, H., Norcliffe-Kaufmann, L., & Palma, J.-A. (2020). Midodrine for orthostatic hypotension. Cochrane Database of Systematic Reviews, 2020(11), CD004890.
4. Costa-Pinto, R., Mårtensson, J., Bellomo, R., et al. (2022). Midodrine use in critically ill patients: A narrative review. Critical Care and Resuscitation, 24(4), 329–338.
5. DailyMed. (2023). Midodrine hydrochloride tablets prescribing information. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov