From the Guidelines
Midodrine should be initiated at a dose of 2.5 mg three times daily and titrated up to 10 mg three times daily as needed, with a maximum daily dose of 30 mg, to manage orthostatic hypotension while minimizing the risk of supine hypertension, as recommended in the 2023 ACC expert consensus decision pathway 1. The goal of midodrine therapy is to increase standing systolic blood pressure by at least 10-15 mmHg without causing excessive supine hypertension.
- Key considerations for midodrine therapy include:
- Starting with a low dose and titrating up as needed to minimize adverse effects
- Avoiding evening doses to prevent supine hypertension during sleep
- Monitoring blood pressure in both supine and standing positions before and after initiating therapy, and periodically during dose adjustments
- Discontinuing or reducing the dose if supine systolic blood pressure exceeds 180 mmHg or if the patient experiences significant adverse effects
- Midodrine works as an alpha-1 adrenergic agonist that increases peripheral vascular resistance, thereby raising blood pressure, and is particularly useful for orthostatic hypotension, but requires careful monitoring to balance symptom relief with the risk of supine hypertension, as noted in a study on the treatment of orthostatic hypotension 1.
- The dosing of midodrine should be individually tailored, with the first dose taken before arising and use avoided several hours before planned recumbency, particularly in patients with documented supine hypertension, as recommended in the study 1.
From the FDA Drug Label
Midodrine forms an active metabolite, desglymidodrine, that is an alpha1-agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. The plasma levels of the prodrug peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about 3 to 4 hours. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93% Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10 mg dose of midodrine, with some effect persisting for 2 to 3 hours.
Midodrine Parameters:
- Onset of Action: 1 hour
- Peak Blood Concentration: 1-2 hours
- Half-life: 3-4 hours (desglymidodrine), 25 minutes (midodrine)
- Bioavailability: 93%
- Effect on Blood Pressure: elevation of standing systolic blood pressure by 15-30 mmHg at 1 hour after a 10 mg dose, with some effect persisting for 2-3 hours 2
From the Research
Midodrine Parameters
- Midodrine is a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration 3.
- The drug significantly increases 1-minute standing systolic blood pressure compared with placebo, and improves standing time and energy level and clinical symptoms of orthostatic hypotension including dizziness, light-headedness and syncope 3.
- Midodrine has similar efficacy to dihydroergotamine mesylate, norfenefrine, fludrocortisone and etilefrine, and is more effective than dimetofrine and ephedrine in patients with orthostatic hypotension 3, 4.
- The most commonly reported adverse events are piloerection, pruritus, paraesthesias, urinary retention and chills 3, and the risk of supine hypertension can be reduced by taking the final daily dose at least 4 hours before bedtime 3.
Dosage and Administration
- A 10-mg dose of midodrine prescribed two to three times daily is effective in increasing orthostatic blood pressure and ameliorating symptoms in patients with neurogenic orthostatic hypotension 5.
- The half-life of desglymidodrine, the active metabolite of midodrine, is approximately 4 hours 5.
- Midodrine dose-blood pressure response, pharmacokinetics, and duration of action were examined in a double-blind, placebo-controlled, four-way crossover trial, which showed a significant linear relation between midodrine dosage and mean systolic blood pressure 5.
Adverse Effects
- Common side effects of midodrine include bradycardia, supine hypertension, and paresthesia 6.
- A novel side effect of midodrine-induced nightmares has been reported, which is thought to be related to autonomic dysfunction 6.
- The timing of administration, including an evening dose, may contribute to the occurrence of midodrine-induced nightmares 6.