Midodrine

ED / ICU / Transport

• Symptomatic orthostatic hypotension (OH): The FDA label covers this. Daily life is considerably impaired, and non-drug measures (compression, fluids, salt, lifestyle changes) have not fixed it.
• Neurogenic OH from autonomic failure (Parkinson disease, multiple system atrophy, pure autonomic failure, autonomic neuropathies): This is the main use. Neurology or cardiology usually starts it, and the ED sees it as a home medication.
• OH after spinal cord injury (T6 and above): Symptomatic OH sits inside the label. The spinal cord medicine guideline suggests drug therapy for symptomatic or asymptomatic OH once non-drug measures fail. The evidence is expert opinion of low quality. Treating asymptomatic OH is off-label.
• Hepatorenal syndrome with acute kidney injury (HRS-AKI): Hepatology directs this use, and it is off-label. It is combined with octreotide and albumin. Terlipressin is the vasoactive drug of choice. Norepinephrine is the ICU alternative.
• Persistent low-dose vasopressor dependence in the ICU: Clinicians sometimes try it to speed vasopressor weaning. That use is off-label. The MIDAS randomized trial found no benefit, so routine use is not supported.

Other Uses

• Recurrent vasovagal syncope: A specialist directs prevention in younger, otherwise healthy patients with frequent episodes. It is off-label. In a 12-month randomized trial, recurrence fell from 61% to 42%. Avoid it in urinary retention and severe organic heart disease. Both are label contraindications.
• Intradialytic hypotension: Some patients take it before hemodialysis. Nephrology directs that, and it is off-label. A 2018 US cohort compared 1,046 midodrine users with 2,037 matched controls. Midodrine was linked to higher death (adjusted IRR 1.37) and more all-cause and cardiovascular hospitalization. The hemodynamic data also hinted at a bigger fall in SBP during dialysis. None of this points to a potent benefit, and residual confounding is possible. No dose is given here. Hemodialysis removes midodrine, so the dialysis team sets the timing.

Don't reach for midodrine in acute hypotension or shock. It is an oral prodrug, and its effect is delayed and short. Vasoconstrictors are not used for uncomplicated ascites, after large-volume paracentesis or for spontaneous bacterial peritonitis.

Start low and titrate to symptoms. The label dose is 10 mg TID (30 mg/day).

Available Forms

• Oral tablets: 2.5 mg, 5 mg and 10 mg midodrine hydrochloride (scored); generics only in the US
• No IV form: EMS does not carry it. Patients take it at home, or the hospital gives it on a schedule.

Adult Dosing

Pediatric Dosing

Preparation & Administration

• Schedule: about every 4 hr while upright: shortly before or on getting up, midday and late afternoon (not later than 6 PM)
• Last dose: not after the evening meal and at least 4 hr before bedtime (the neurogenic OH consensus advises 5 hr)
• Position: Give it only when the patient will be upright. If they will lie flat for any length of time, skip the dose.
• Food: With or without food. Bioavailability is not affected.
• Hospital orders: Ask for timed doses, for example 08:00, 12:00 and 16:00. A generic TID or every-8-hr schedule can land a dose at night.

Contraindications

• Severe organic heart disease
• Acute renal disease
• Urinary retention
• Pheochromocytoma
• Thyrotoxicosis
• Persistent and excessive supine hypertension

Precautions

• Baseline supine SBP above 180 mmHg: Trials excluded these patients, so there is no trial experience to go on. The label does not recommend use.
• Drugs or conditions that slow the heart rate (digoxin, beta-blockers, psychotropic drugs): Midodrine causes reflex slowing. Watch for bradycardia.
• Prostate enlargement, neurogenic bladder: Stimulating α₁ receptors at the bladder neck can cause retention.
• Diabetes, or visual problems with fludrocortisone co-therapy: use with caution, per the label.
• Renal or hepatic impairment: not studied in these patients. Start low (see Special Populations).
• OTC cold remedies and diet aids: decongestants stack on the pressor effect.

Hold / Reassess If

• Supine SBP above 180 mmHg, or symptoms of supine hypertension (pounding in the ears, headache, blurred vision, cardiac awareness): hold, sit the patient up, recheck and notify the prescriber
• Pulse slowing with dizziness, syncope or cardiac awareness: hold, get an ECG, re-evaluate
• Unable to void or a palpable bladder: hold, bladder scan
• Patient will be supine for hours (procedure, prolonged bed rest, bedtime): skip the dose
• Spinal cord injury and a cystoscopic or other urologic procedure planned: hold as-needed midodrine beforehand (autonomic dysreflexia risk)
• No clear symptomatic improvement: the label says stop it

Common

• Paresthesia, mainly scalp tingling (18%)
• Piloerection (goosebumps) (13%)
• Urinary symptoms: urgency, frequency, dysuria, retention (13%)
• Pruritus, mainly scalp (12%)
• Supine hypertension (7% in the 3-week trial)
• Chills (5%)
• Less often: headache, head pressure, facial flushing, confusion, dry mouth, anxiety, rash

Serious / Life-Threatening

The percentages here come from the US label (DailyMed: adverse reactions, warnings and clinical pharmacology). They do not come from the trials in References.

Overdose & Toxicity Management

• Picture: hypertension, piloerection (goosebumps), a sensation of coldness and urinary retention (label overdosage section)
• Immediate management: airway, BP and ECG monitoring, upright positioning; call Poison Control (1-800-222-1222)
• Severe hypertension: an α-blocker such as phentolamine (dose per toxicology/Poison Control). Pediatric dosing per toxicology
• Extracorporeal removal: Desglymidodrine can be removed by dialysis.

Clinically Significant Interactions

It is oral only, so IV compatibility does not come up.

• Pediatrics: Safety, effectiveness and dosing are not established. Only specialists use it. See Pediatric Dosing.
• Pregnancy: There are no adequate human data. In rats and rabbits, doses 7–13 times the maximum human dose raised embryo resorption and cut fetal weight. In rabbits, fetal survival fell as well. No malformations were seen. Use it only if the benefit justifies the risk. It has no role in acute hypotension in pregnancy.
• Lactation: It is not known whether it passes into human milk. Use with caution and involve the prescriber.
• Older Adults: Blood levels are similar at 65 and older. The label calls for no age-based change. In practice, the risks are supine hypertension, urinary retention from prostate enlargement, and bradycardia with rate-slowing co-medications.
• Renal Impairment: Desglymidodrine is renally secreted. Check renal function, start with 2.5 mg per dose and titrate cautiously. Acute renal disease is a contraindication. Hemodialysis removes midodrine, so coordinate dose timing with the dialysis team.
• Hepatic Impairment: Not studied. The liver contributes to metabolism, so use with caution. No specific adjustment is established.
• Obesity / Dosing Weight: Doses are fixed, with no weight-based adjustment.
• Neurogenic OH with Supine Hypertension: It is common in autonomic failure. The 2018 AAS/EFAS consensus defines neurogenic supine hypertension as SBP ≥140 and/or DBP ≥90 mmHg after at least 5 min lying flat. It calls the condition severe at SBP ≥180 or DBP ≥110 mmHg. Manage it with head-up sleeping (head 15–23 cm, 6–9 inches, above the feet). Add a short-acting bedtime antihypertensive only if needed, chosen by the treating team.

• Scope: EMS does not carry it. You meet it as a home medication in patients with syncope, falls or Parkinson disease. Hospital and transport RNs give scheduled doses per orders, and the rules vary by state and agency protocol.
• Position With Every BP: A patient who took a dose in the past few hours can be hypertensive flat on the stretcher and hypotensive once sat up. Record the position with each reading. Raise the head of the stretcher before you treat a supine number.
• Syncope Calls: ask about recent dose changes, missed doses, decongestants and new blood-pressure drugs; check orthostatic vitals if the patient can stand safely.
• Spinal Cord Injury at T6 or Above: A sudden SBP rise of more than 20 mmHg above the person's baseline in adults (more than 15 mmHg in children and adolescents), with headache or flushing, is autonomic dysreflexia until proven otherwise. Sit up, lower the legs, loosen clothing and find the trigger, bladder first. Ask about recent midodrine. It adds to the rise. BP can climb again after a short-acting antihypertensive wears off, so monitor longer.
• Interfacility Transfers: for ICU patients on midodrine during a vasopressor wean, confirm the MAP target, current vasopressor dose and when the next midodrine dose is due; watch for bradycardia.
• Storage & Stability: 20–25 °C (68–77 °F), tight light-resistant container.
• Handoff Essentials: dose and time of the last midodrine tablet, supine and upright BP with positions, heart rate, voiding status.

Mechanism of Action

• The prodrug is deglycinated in many tissues into desglymidodrine, the active α₁-adrenergic agonist.
• α₁ stimulation tightens arterioles and veins. Vascular tone rises, and standing SBP climbs about 15–30 mmHg, 1 hr after 10 mg.
• No cardiac β stimulation. The pulse barely changes in autonomic failure, though reflex slowing can happen.
• Poor blood-brain barrier penetration means no CNS stimulation.
• The same α₁ effects on the bladder neck and hair follicles cause urinary retention, piloerection and scalp paresthesia.

Pharmacokinetics

• Half-life: midodrine about 25 min; desglymidodrine about 3–4 hr
• Bioavailability: 93% (as desglymidodrine); not affected by food
• Metabolism: deglycination in many tissues, partly hepatic; not a monoamine oxidase substrate
• Elimination: desglymidodrine renal clearance about 385 mL/min, about 80% by active tubular secretion; removed by hemodialysis
• Protein binding: not significant

Generic Name

Midodrine hydrochloride

Brand Names

ProAmatine (discontinued in the US, not for safety or effectiveness reasons); Orvaten (approved branded generic; may not be currently marketed); multiple generics

Pharmacologic Class

α₁-Adrenergic agonist (prodrug of desglymidodrine)

Therapeutic Class

Antihypotensive; vasopressor for orthostatic hypotension

Controlled Substance

Not controlled

ISMP High-Alert

No (oral; not on the ISMP acute-care list)

Look-Alike / Sound-Alike

midodrine / Midrin (ISMP confused drug names list); confirm the indication on any order