From the Guidelines
Yes, midodrine and fludrocortisone (Florinef) can be given together for hypotension when a single agent is insufficient, as recommended by the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1. This combination therapy targets different mechanisms: midodrine is an alpha-1 agonist that causes peripheral vasoconstriction, while fludrocortisone is a mineralocorticoid that increases sodium retention and blood volume. Typical dosing for midodrine is 2.5-10 mg three times daily (morning, midday, and late afternoon but not after 6 PM to avoid supine hypertension during sleep), while fludrocortisone is usually started at 0.1 mg daily and titrated as needed up to 0.2-0.3 mg daily. Some key points to consider when using this combination include:
- Close monitoring of blood pressure (both sitting and standing), electrolytes, and renal function is essential.
- Patients should be educated about potential side effects including supine hypertension, headache, piloerection, urinary retention with midodrine, and fluid retention, hypokalemia, and edema with fludrocortisone.
- Adequate salt and fluid intake should be maintained, particularly with fludrocortisone therapy.
- This combination is particularly useful in neurogenic orthostatic hypotension or refractory hypotension cases where single-agent therapy has failed, as supported by the 2017 ACC/AHA/HRS guideline 1 and other studies 1.
The most recent and highest quality study, the 2017 ACC/AHA/HRS guideline 1, provides the best evidence for this recommendation, and it should be prioritized in clinical decision-making. It's also important to note that the potential risks of a drug should be weighed against its possible benefit, including the balance between the goal of increasing standing blood pressure and the avoidance of a marked supine hypertension, as mentioned in the study by 1. Overall, the combination of midodrine and fludrocortisone can be a useful treatment option for patients with hypotension, particularly those with neurogenic orthostatic hypotension or refractory hypotension.
From the FDA Drug Label
Midodrine has been used in patients concomitantly treated with salt-retaining steroid therapy (i.e., fludrocortisone acetate), with or without salt supplementation. The use of midodrine with fludrocortisone (florinef) may be done, but caution is advised to monitor for supine hypertension.
- Key considerations:
- Monitor blood pressure closely
- Be aware of the potential for supine hypertension
- Adjust the dose of fludrocortisone acetate or decrease salt intake as needed 2
From the Research
Treatment of Hypotension with Midodrine and Fludrocortisone
- Midodrine and fludrocortisone are two medications used to treat hypotension, particularly orthostatic hypotension 3, 4, 5, 6, 7.
- Midodrine is a peripheral alpha-adrenergic agonist that increases standing blood pressure and improves symptoms of orthostatism 3, 4.
- Fludrocortisone is a mineralocorticoid analog that promotes sodium reabsorption and is also used to treat orthostatic hypotension 5, 6, 7.
Comparison of Midodrine and Fludrocortisone
- Studies have compared the efficacy and safety of midodrine and fludrocortisone in patients with orthostatic hypotension 5, 6, 7.
- One study found that midodrine was associated with a lower risk of all-cause hospitalizations compared to fludrocortisone 5.
- Another study found that both midodrine and fludrocortisone were effective in increasing 24-hour systolic blood pressure and reducing systolic blood pressure drops, but fludrocortisone seemed to be more effective than midodrine 7.
Combination Therapy
- There is limited evidence on the use of combination therapy with midodrine and fludrocortisone for hypotension 7.
- One study found that combination therapy with midodrine and fludrocortisone increased 24-hour systolic blood pressure and reduced systolic blood pressure drops, but further randomized studies are needed to confirm these observations 7.