MIDODRINE HYDROCHLORIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Midodrine is a prodrug that is metabolized to desglymidodrine, an alpha1-adrenergic receptor agonist. Desglymidodrine increases peripheral arterial and venous tone, leading to increased blood pressure through vasoconstriction.

What the body does with it

Metabolism	Midodrine is rapidly hydrolyzed by enzymatic hydrolysis (likely via esterases) in the liver and systemic circulation to its active metabolite, desglymidodrine. Minor metabolism via hydroxylation and glucuronidation. Poor metabolizer status (CYP2D6) may affect metabolism of midodrine itself but not desglymidodrine.
Excretion	Renal excretion: approximately 80% as unchanged drug and active metabolite (desglymidodrine). Biliary/fecal: minor (<10%).
Half-life	Midodrine: ~0.5 hours; desglymidodrine: ~2-4 hours (terminal half-life). Clinical context: dosing every 3-4 hours to maintain effect.
Protein binding	Midodrine: ~21-33% (primarily albumin); desglymidodrine: ~53-66% (albumin).
Volume of Distribution	Midodrine: ~4 L/kg; desglymidodrine: ~1.5 L/kg. Reflects extensive tissue distribution.
Bioavailability	Oral: ~93% (midodrine) converted to active metabolite; absolute bioavailability of midodrine itself is low due to first-pass metabolism.
Onset of Action	Oral: 30-60 minutes to increase standing systolic blood pressure.
Duration of Action	Oral: 2-4 hours (pressor effect). Clinical note: avoid dosing within 4 hours of bedtime to prevent supine hypertension.

Classification & Brands

Dosing & administration

5-10 mg orally every 8 hours during daytime hours (last dose before evening meal to prevent supine hypertension).

Dosage form	TABLET
Renal impairment	Contraindicated in acute renal disease. Not recommended if eGFR <30 mL/min/1.73 m². For moderate impairment (eGFR 30-59): reduce dose to 2.5 mg every 8 hours if necessary.
Liver impairment	No specific Child-Pugh based adjustments available. Use with caution in severe hepatic impairment due to potential for increased exposure; consider dose reduction.
Pediatric use	Safety and efficacy not established in pediatric patients; no FDA-approved dosing guidelines.
Geriatric use	Initiate at lower dose (2.5 mg every 8 hours) due to increased risk of supine hypertension and reduced renal function. Titrate cautiously based on blood pressure response.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Other vasoconstrictors can have additive effects Can cause supine hypertension and bradycardia.

Breastfeeding	No data on excretion in human milk; M/P ratio unknown. Due to potential for cardiovascular effects in infant (hypertension, bradycardia), caution advised. Consider alternative therapies.
Teratogenic Risk	Insufficient human data; animal studies show no teratogenic effects at clinically relevant doses. Use only if potential benefit outweighs risk. First trimester: unknown risk; second/third trimester: may cause fetal bradycardia and hypertension due to alpha-adrenergic stimulation.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Supine hypertension
Serious Effects

Absolute Contraindications

Severe organic heart disease (e.g., aortic stenosis, heart failure), acute renal failure, urinary retention, pheochromocytoma, thyrotoxicosis, persistent and significant supine hypertension (≥180/110 mmHg), concurrent use of potent vasoconstrictors like ergot alkaloids or MAO inhibitors.

Clinical Precautions

Precautions

Supine hypertension is the most serious adverse effect; monitor supine blood pressure. Use with caution in patients with renal impairment (dose reduction required for CrCl < 30 mL/min). Avoid in patients with severe organic heart disease, history of urinary retention, or hyperthyroidism. May cause bradycardia, piloerection, pruritus, and paresthesia. Discontinue if severe hypertension or symptoms of excessive vasoconstriction occur.

Clinical Tips & Counseling

Drug interactions

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