What is the recommended dose of midodrine for treating hypotension?

Midodrine Dosing for Hypotension

The recommended dose of midodrine for treating hypotension is 10 mg three times daily, with doses spaced approximately 4 hours apart during daytime hours when the patient is upright, and the last dose should not be given after 6 PM or within 4 hours of bedtime to avoid supine hypertension. 1

Standard Dosing Regimen

• Start with 10 mg three times daily as the standard therapeutic dose for orthostatic hypotension 1, 2
• Administer doses at approximately 4-hour intervals: upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
• Doses may be given at 3-hour intervals if needed to control symptoms, but not more frequently 1

Dose Titration Strategy

Initial Dosing in Special Populations

• Patients with renal impairment: Start with 2.5 mg doses and titrate cautiously, as the active metabolite desglymidodrine is renally excreted 1
• Patients with severe symptoms: May require up to 20 mg per dose, though this carries a 45% risk of severe supine hypertension 1

Dose Escalation

• The 10 mg dose produces a 22-28 mmHg increase in standing systolic blood pressure (approximately 27-28% improvement) 3, 4
• Lower doses (2.5-5 mg) may be effective in diabetic autonomic neuropathy patients 5
• Maximum single dose studied is 20 mg, but routine use at this level is not recommended due to high rates of supine hypertension 1, 6
• Total daily doses should not exceed 30 mg (10 mg three times daily) for routine use 1

Context-Specific Dosing

Orthostatic Hypotension in Autonomic Failure

• First-line pharmacologic therapy after non-pharmacological measures fail 2
• Titrate individually up to 10 mg two to four times daily, with first dose taken before arising 2
• Particularly effective in Shy-Drager syndrome and Bradbury-Eggleston syndrome, producing 22 mmHg increases in standing systolic pressure 5

Hepatorenal Syndrome-AKI

• Oral midodrine 7.5 mg initially, titrated upward to 12.5 mg three times daily 2
• Used in combination with octreotide (100-200 mcg subcutaneously three times daily) and albumin 2
• Continue until serum creatinine returns to within 0.3 mg/dL of baseline or for maximum 14 days 2

Refractory Ascites in Cirrhosis

• 7.5 mg three times daily in non-azotemic patients with ascites 2
• Results in significant increases in mean arterial pressure and urine sodium excretion 2
• Consider on a case-by-case basis as adjunctive therapy 2

Intradialytic Hypotension

• Single 5 mg dose administered 30 minutes before dialysis session 2
• Effectively cleared by hemodialysis with half-life reduced to 1.4 hours during dialysis 2
• Can be used long-term (>8 months) without adverse events 2

Pharmacokinetics and Duration of Action

• Peak effect occurs at 1 hour post-dose 6
• Half-life of active metabolite (desglymidodrine) is approximately 4 hours 6
• This pharmacokinetic profile supports dosing 2-3 times daily for sustained effect 6
• Blood levels are similar across age groups (≥65 vs <65 years) and sex, requiring no dose adjustments for these factors 1

Critical Safety Considerations

Timing Restrictions

• Never administer after evening meal or within 4 hours of bedtime to prevent nocturnal supine hypertension 1, 2
• Patients should sleep with head of bed elevated 10 degrees to mitigate supine hypertension risk 2

Monitoring Requirements

• Monitor supine and standing blood pressure regularly 1
• Discontinue if supine blood pressure increases excessively 1
• Continue therapy only if symptomatic improvement is documented during initial treatment 1
• Watch for reflex bradycardia due to parasympathetic stimulation 2

Common Adverse Effects

• Pilomotor reactions (scalp tingling/pruritus) occur in approximately 13.5% of patients 4
• Supine hypertension in 8% of patients 4
• Urinary urgency/retention in 4% 4, 2
• Other effects: nausea, heartburn, headache, nervousness 2

Drug Interactions and Contraindications

• Use cautiously with: beta-blockers, digoxin, non-dihydropyridine calcium channel blockers, and in patients with congestive heart failure 2
• Avoid concurrent use with: other alpha-adrenergic agents (ephedrine, pseudoephedrine, phenylpropanolamine) as this aggravates supine hypertension 2
• May antagonize: alpha-adrenergic blockers (terazosin, prazosin, doxazosin), potentially causing urinary retention 2

Treatment Algorithm

1. Initiate non-pharmacological measures first: adequate hydration, salt intake (10g NaCl daily), compression garments, physical counterpressure maneuvers, head-up sleeping 2
2. If symptoms persist, start midodrine 10 mg three times daily (or 2.5 mg in renal impairment) 1, 2
3. Assess response after 1-2 weeks: measure standing systolic BP improvement and symptom relief 3, 4
4. Adjust dose based on response: may increase to 20 mg per dose if needed, but monitor closely for supine hypertension 1
5. Discontinue if no symptomatic improvement or if supine hypertension develops 1