What is the recommended dosage and treatment approach for midodrine (ProAmatine) in managing orthostatic hypotension?

From the Guidelines

Midodrine (ProAmatine) is recommended as a first-line treatment for orthostatic hypotension, with a typical starting dose of 2.5 mg three times daily, titrated up to 10 mg three times daily based on blood pressure response and tolerance. The medication works as an alpha-1 adrenergic agonist that causes peripheral vasoconstriction, increasing blood pressure to counteract orthostatic hypotension 1. Treatment should be individualized, with careful monitoring of both standing and supine blood pressures. Patients should be instructed to take the medication before activities that trigger symptoms, such as prolonged standing or in the morning when symptoms are often worst.

Mechanism of Action

The mechanism of action of midodrine involves the selective activation of alpha-1 adrenergic receptors, leading to arteriolar constriction and venoconstriction of capacitance vessels, which increases blood pressure 1. This effect is beneficial in patients with orthostatic hypotension, as it helps to counteract the decrease in blood pressure that occurs upon standing.

Dosage and Administration

The dosing of midodrine should be individually tailored, with a typical dose range of 2.5-10 mg three times daily, taken during waking hours, approximately 3-4 hours apart, with the last dose at least 3-4 hours before bedtime to avoid supine hypertension 1.

Non-Pharmacological Measures

Non-pharmacological measures should be used concurrently with midodrine, including:

• Adequate hydration (2-3 liters of fluid daily)
• Increased salt intake (unless contraindicated)
• Compression stockings
• Avoiding rapid position changes
• Head-up bed position during sleep
• Physical counter-manoeuvres (e.g. leg-crossing, stooping, squatting, and tensing muscles) 1

Common Side Effects

Common side effects of midodrine include piloerection (goosebumps), scalp tingling, urinary retention, and supine hypertension 1. The medication is contraindicated in patients with severe cardiac disease, acute renal failure, urinary retention, pheochromocytoma, or thyrotoxicosis.

From the FDA Drug Label

The recommended dose of midodrine hydrochloride tablets is 10 mg, 3 times daily. Dosing should take place during the daytime hours when the patient needs to be upright, pursuing the activities of daily living A suggested dosing schedule of approximately 4-hour intervals is as follows: shortly before, or upon arising in the morning, midday and late afternoon (not later than 6 P.M.)

The recommended dosage for midodrine (ProAmatine) in managing orthostatic hypotension is 10 mg, 3 times daily. The treatment approach involves dosing during daytime hours, with a suggested schedule of approximately 4-hour intervals, and not giving doses after the evening meal or less than 4 hours before bedtime to reduce the potential for supine hypertension during sleep 2.

• Dosing intervals: approximately 4-hour intervals, or 3-hour intervals if required to control symptoms
• Maximum daily dose: Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established
• Monitoring: The supine and standing blood pressure should be monitored regularly, and the administration of midodrine hydrochloride tablets should be stopped if supine blood pressure increases excessively 2.

From the Research

Mechanism of Action for Midodrine

• Midodrine is a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration 3, 4.
• The drug increases standing blood pressure and improves symptoms of orthostatism, such as weakness, syncope, blurred vision, and fatigue, without any associated cardiac stimulation 4.
• Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine 4.

Recommended Dosage and Treatment Approach

• The recommended dosage of midodrine for orthostatic hypotension is not explicitly stated in the provided studies, but it is mentioned that the final daily dose should be taken at least 4 hours before bedtime to reduce the risk of supine hypertension 3.
• Midodrine can be used as a single therapy or in combination with other drugs, such as pyridostigmine, for the treatment of neurogenic orthostatic hypotension 5.
• The treatment approach for orthostatic hypotension may involve a combination of nonpharmacological and pharmacological interventions, including midodrine, fludrocortisone, and other agents 3, 6.

Efficacy and Safety of Midodrine

• Midodrine has been shown to be effective in increasing standing blood pressure and improving symptoms of orthostatic hypotension in several studies 3, 4, 7.
• The drug is generally well-tolerated, with common adverse events including piloerection, pruritus, paraesthesias, urinary retention, and chills 3, 4.
• Midodrine has been compared to other agents, such as fludrocortisone, pyridostigmine, and dihydroergotamine, and has been found to be at least as effective in managing orthostatic hypotension 3, 4, 5.