Fludrocortisone

●  Brand Name: Florinef

●  Indication: While typically used to treat adrenal insufficiency, several studies suggest that this drug may be effective off-label in managing neurocardiogenic syncope and POTS when combined with increased salt intake and other medications, such as a low- dose beta blocker. However, no rigorous studies have been conducted on combination therapy, and there are no studies specifically involving adolescents.

●  Contraindication: those with systemic fungal infections or known hypersensitivity to fludrocortisone.

●  Mechanism of Action: Florinef is a mineralocorticoid steroid that acts on the kidneys to promote sodium retention, helping the body retain salt that would otherwise be excreted in the urine. However, this process can lead to potassium loss, making it important to ensure sufficient potassium intake. It is generally recommended to begin potassium supplements when starting Florinef, regardless of the initial potassium levels, especially if the medication is used long-term. A sustained-release potassium supplement (20 mEq) taken once daily is typically well tolerated. Ongoing dietary monitoring and potassium supplementation may be necessary with prolonged use. Additionally, Florinef may enhance the ability of blood vessels to constrict in response to hormones like epinephrine and norepinephrine.

●  Side Effects: To reduce the chance of Florinef causing an elevated blood sodium level, make sure to drink lots of fluids while taking Florinef. Some individuals complain of headache, weight gain, and some develop worse CFS symptoms (more lightheadedness or fatigue), abdominal discomfort of a new type or severity, new chest discomfort, or tearfulness and depression. Depression occurs in fewer than 1 in 20 patients, but patients need to be aware of this when they start on the drug, and to know to stop Florinef if such depressed mood occurs. Some minor side effects of Florinef may subside after a few weeks, and it is generally worth continuing the medication if the side effects are mild. However, it can cause worsened acne and discomfort in individuals highly sensitive to milk protein due to trace amounts of lactose in the tablet; lactose-free formulations are available. At high doses or with prolonged use, Florinef can raise blood pressure, particularly when combined with other medications like oral contraceptives. Regular blood pressure monitoring is recommended, especially in the initial weeks and monthly once a stable dose is reached.

●  Dosage: Because the optimal dose of Florinef varies, it’s recommended to start with a low dose and increase gradually. Begin by increasing salt and fluid intake for a week before starting Florinef to improve tolerance. Start with 1⁄2 tablet daily for one week, then increase to a full 0.1 mg tablet. Alternatively, start with 1⁄4 tablet per day, and if tolerated for 4-7 days, increase to 1⁄2 tablet, then 3⁄4 tablet or a full 0.1 mg. Some patients find splitting the dose (half in the morning, half with dinner) helps with effects, but others may need to return to a once-daily morning dose due to insomnia. As each patient responds differently, regular follow-up visits are recommended during dose adjustments. If there’s no improvement or significant side effects, discontinue the medication. If there is some benefit at a particular dose, maintain it. If 0.1 mg daily doesn’t provide sufficient benefit after a month, consider increasing the dose to 0.15 or 0.2 mg per day. If unsure whether the drug is effective, it can be paused for a few days to assess symptom changes. When Florinef is partially helpful, it is usually continued in combination with other medications.

●  Reproductive and Pregnancy Considerations: There are no specific studies on the use of fludrocortisone during pregnancy or lactation; however, data on glucocorticoid use during pregnancy indicate an increased risk of cleft palate and potential fetal growth restrictions. The American Academy of Pediatrics deems glucocorticoids compatible with breastfeeding.

Citations

AHFS drug information 2006. McEvoy GK, ed. Fludrocortisone. Bethesda, MD: American Society of Health-System Pharmacists; 2006: 2997-98

Bryarly, M., Phillips, L. T., Fu, Q., Vernino, S., & Levine, B. D. (2019). Postural Orthostatic Tachycardia Syndrome: JACC Focus Seminar. Journal of the American College of Cardiology, 73(10), 1207–1228. https://doi.org/10.1016/j.jacc.2018.11.059

Lahrmann, H., Cortelli, P., Hilz, M., Mathias, C. J., Struhal, W., & Tassinari, M. (2006). EFNS guidelines on the diagnosis and management of orthostatic hypotension. European journal of neurology, 13(9), 930–936. https://doi.org/10.1111/j.1468-1331.2006.01512.x

Lunghi, L., Pavan, B., Biondi, C., Paolillo, R., Valerio, A., Vesce, F., & Patella, A. (2010). Use of glucocorticoids in pregnancy. Current pharmaceutical design, 16(32), 3616–3637. https://doi.org/10.2174/138161210793797898

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