Is midodrine a suitable medication for daily use?

From the Guidelines

Midodrine can be beneficial for daily use in patients with syncope due to neurogenic orthostatic hypotension, but its use should be carefully monitored due to potential side effects such as supine hypertension, scalp tingling, piloerection, and urinary retention. According to the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1, midodrine improves symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension, with a dose-dependent effect corresponding to an increase in standing blood pressure. However, its use may be limited by supine hypertension, and other common side effects include scalp tingling, piloerection, and urinary retention.

The dosing of midodrine should be individually tailored, with typical doses ranging from 2.5 to 10 mg taken 2-3 times daily, as noted in the 2011 study on cardiovascular autonomic neuropathy in diabetes 1. It is essential to weigh the potential risks of midodrine against its possible benefits, including the balance between increasing standing blood pressure and avoiding marked supine hypertension. Alternative approaches, such as increased salt and fluid intake, compression stockings, and lifestyle modifications, should be considered before committing to daily midodrine use.

Some key points to consider when using midodrine daily include:

• Regular monitoring by a healthcare provider to minimize the risk of supine hypertension and other side effects
• Individualized dosing to balance the benefits and risks of midodrine
• Consideration of alternative treatments, such as increased salt and fluid intake, compression stockings, and lifestyle modifications, before initiating daily midodrine use
• Education of patients on behavioral strategies, such as gradual staged movements with postural change, mild isotonic exercise, and head-up bed position during sleep, to help manage orthostatic hypotension.

From the FDA Drug Label

The potential for supine and sitting hypertension should be evaluated at the beginning of midodrine therapy. Midodrine should be used cautiously in patients with urinary retention problems, as desglymidodrine acts on the alpha-adrenergic receptors of the bladder neck Midodrine should be used with caution in orthostatic hypotensive patients who are also diabetic, as well as those with a history of visual problems who are also taking fludrocortisone acetate, which is known to cause an increase in intraocular pressure and glaucoma. Midodrine use has not been studied in patients with renal impairment Midodrine use has not been studied in patients with hepatic impairment. Patients should be told that certain agents in over-the-counter products, such as cold remedies and diet aids, can elevate blood pressure, and therefore, should be used cautiously with midodrine, as they may enhance or potentiate the pressor effects of midodrine

Midodrine is not necessarily a good medication to use daily for everyone, as it can cause supine hypertension and has potential interactions with other medications.

• Caution is advised when using midodrine in patients with certain medical conditions, such as urinary retention problems, diabetes, visual problems, renal impairment, or hepatic impairment.
• Monitoring of blood pressure is necessary when using midodrine, especially when used concomitantly with other agents that cause vasoconstriction.
• The dosage and administration of midodrine should be individualized and carefully monitored to minimize the risk of supine hypertension 2 2.

From the Research

Efficacy of Midodrine

• Midodrine is effective in increasing standing blood pressure and improving symptoms of orthostatic hypotension, such as weakness, syncope, blurred vision, and fatigue 3, 4.
• Comparative studies have shown midodrine to be clinically at least as effective as other sympathomimetic agents and dihydroergotamine in managing orthostatic hypotension 3, 4.
• Midodrine has been found to cause less frequent and severe adverse effects associated with alpha-receptor agonism, such as piloerection and urinary hesitancy 3.

Safety and Tolerability

• Midodrine is generally well-tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention, and chills 4.
• The risk of supine hypertension, which is associated with midodrine therapy in up to 25% of patients, can be reduced by taking the final daily dose at least 4 hours before bedtime 4.
• A novel side effect of midodrine-induced nightmares has been reported in a case study, highlighting the importance of careful consideration when prescribing midodrine in older people with orthostatic hypotension 5.

Combination Therapy

• Single or combination treatment with midodrine and pyridostigmine has been found to be effective and safe in patients with orthostatic hypotension for up to 3 months 6.
• Midodrine was better than pyridostigmine at improving orthostatic hypotension-related symptoms 6.

Treatment Guidelines

• Midodrine is considered a viable treatment option for primary orthostatic hypotension, with evidence supporting its efficacy in increasing blood pressure and alleviating symptoms 7.
• Medication management of primary orthostatic hypotension should be guided by patient-specific factors, such as tolerability, adverse effects, and drug-drug and drug-disease interactions 7.