From the Guidelines
Elderly patients with symptomatic orthostatic hypotension should generally receive lower maximum doses of midodrine, typically 5 mg TID instead of 10 mg TID, due to the risk of supine hypertension and other adverse effects. According to the study by 1, midodrine is a first-line drug that exerts a pressor effect through both arteriolar constriction and venoconstriction of the capacitance vessels, but it can cause adverse events such as supine hypertension, bradycardia, gastrointestinal symptoms, and urinary retention.
When uptitrating midodrine to 10 mg TID, clinicians should watch for several concerning side effects, including:
- Supine hypertension (potentially severe), which can lead to stroke or cardiovascular events
- Urinary retention or hesitancy, particularly in men with prostatic hyperplasia
- Bradycardia or other cardiac arrhythmias
- Piloerection (goosebumps) or scalp tingling, which may indicate excessive alpha-adrenergic stimulation
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 noted in the study by 1. Patients should be instructed to avoid taking midodrine within 4 hours of bedtime to reduce supine hypertension risk and to have their blood pressure monitored regularly in both standing and supine positions during dose adjustments. Starting at 2.5 mg TID and gradually increasing while monitoring for side effects is the safest approach in elderly patients.
From the FDA Drug Label
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 Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (about 45%) at this dose Dosing in patients with abnormal renal function should be cautious; although this has not been systematically studied, it is recommended that treatment of these patients be initiated using 2.5 mg doses. Blood levels of midodrine and desglymidodrine were similar when comparing levels in patients 65 or older vs. younger than 65 The most frequent adverse reactions seen in controlled trials were supine and sitting hypertension;
Some reasons to have a lower maximum tid midodrine target in elderly patients with symptomatic orthostatic hypotension include:
- Supine hypertension: elderly patients may be more susceptible to excessive supine blood pressure increases, which can be dangerous.
- Renal function: elderly patients may have decreased renal function, which can affect midodrine metabolism and increase the risk of adverse reactions. Some dangerous side-effects to watch out for when uptitrating midodrine to 10 mg tid include:
- Supine hypertension: a potentially serious adverse reaction associated with midodrine therapy.
- Piloerection, paresthesia, and pruritus: pilomotor reactions associated with the action of midodrine on the alpha-adrenergic receptors of the hair follicles.
- Urinary urgency, retention, and frequency: associated with the action of midodrine on the alpha-receptors of the bladder neck. 2, 2, 2
From the Research
Reasons for Lower Maximum Tid Midodrine Target in Elderly Patients
- Elderly patients may be more susceptible to the adverse effects of midodrine, such as supine hypertension, which can occur in up to 25% of patients 3.
- The risk of supine hypertension can be reduced by taking the final daily dose at least 4 hours before bedtime, but this may not be sufficient for all elderly patients 3.
- Elderly patients may also be more prone to other adverse effects, such as piloerection, pruritus, and urinary retention, which can be dose-dependent 3, 4.
- A novel side effect of midodrine-induced nightmares has been reported in an elderly patient, highlighting the need for careful consideration when prescribing midodrine in older people with orthostatic hypotension 5.
Dangerous Side-Effects to Watch Out for with Uptitrating Midodrine to 10 mg DID
- Supine hypertension, which can occur in up to 25% of patients, and can be reduced by taking the final daily dose at least 4 hours before bedtime 3.
- Piloerection, pruritus, and urinary retention, which can be dose-dependent 3, 4.
- Bradycardia, which is a common side effect of midodrine 5.
- Paresthesia, which is a common side effect of midodrine 5.
- Nightmares, which have been reported in an elderly patient, highlighting the need for careful consideration when prescribing midodrine in older people with orthostatic hypotension 5.