From the Guidelines
Florinef (fludrocortisone) can cause several side effects when used to treat hypoadrenocorticism (HA), including fluid retention, hypertension, and electrolyte imbalances, as noted in the 2017 guideline 1. The most common side effects of Florinef include:
- Fluid retention, leading to weight gain, edema, headaches, and dizziness
- Electrolyte imbalances, particularly hypokalemia (low potassium) and hypernatremia (high sodium)
- Hypertension, which can be a concern for patients with pre-existing cardiac conditions
- Increased susceptibility to infections due to immunosuppressive effects
- Worsened glucose control in diabetic patients, as fludrocortisone can increase blood sugar levels These side effects occur because fludrocortisone is a synthetic mineralocorticoid that primarily affects sodium retention and potassium excretion in the kidneys, which is necessary to replace the aldosterone deficiency in hypoadrenocorticism but can lead to these physiological changes when levels become excessive. Regular monitoring of blood pressure, electrolytes, and body weight is essential during treatment with Florinef, as recommended in the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1. Dosage typically starts at 0.1 mg daily and is adjusted based on clinical response and electrolyte levels. Patients should not abruptly discontinue the medication as this could precipitate an adrenal crisis. In terms of management, encouraging increased salt and fluid intake may be reasonable in selected patients with neurogenic OH, as noted in the 2017 ACC/AHA/HRS guideline 1. However, this approach may not be beneficial in patients with a history of hypertension, renal disease, heart failure, or cardiac dysfunction. Overall, the side effects of Florinef can be managed with careful monitoring and adjustment of dosage, as well as consideration of alternative treatments for patients with specific comorbidities or concerns.
From the FDA Drug Label
ADVERSE REACTIONS Most adverse reactions are caused by the drug’s mineralocorticoid activity (retention of sodium and water) and include hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis Musculoskeletal—muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathologic fracture of long bones, and spontaneous fractures. Gastrointestinal—peptic ulcer with possible perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis Dermatologic—impaired wound healing, thin fragile skin, bruising, petechiae and ecchymoses, facial erythema, increased sweating, subcutaneous fat atrophy, purpura, striae, hyperpigmentation of the skin and nails, hirsutism, acneiform eruptions and hives; Neurological—convulsions, increased intracranial pressure with papilledema (psuedo-tumor cerebri) usually after treatment, vertigo, headache, and severe mental disturbances. Endocrine—menstrual irregularities; development of the cushingoid state; suppression of growth in children; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress (e.g., trauma, surgery, or illness); decreased carbohydrate tolerance; manifestations of latent diabetes mellitus; and increased requirements for insulin or oral hypoglycemic agents in diabetics. Ophthalmic—posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos. Metabolic—hyperglycemia, glycosuria, and negative nitrogen balance due to protein catabolism Allergic Reactions—allergic skin rash, maculopapular rash, and urticaria.
The potential side effects of Florinef (fludrocortisone) on Hypoadrenocorticism (HA) include:
- Mineralocorticoid activity: hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis
- Musculoskeletal: muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures
- Gastrointestinal: peptic ulcer with possible perforation and hemorrhage, pancreatitis
- Dermatologic: impaired wound healing, thin fragile skin, bruising
- Neurological: convulsions, increased intracranial pressure with papilledema
- Endocrine: menstrual irregularities, development of the cushingoid state, suppression of growth in children
- Ophthalmic: posterior subcapsular cataracts, increased intraocular pressure, glaucoma
- Metabolic: hyperglycemia, glycosuria, and negative nitrogen balance due to protein catabolism
- Allergic Reactions: allergic skin rash, maculopapular rash, and urticaria 2
From the Research
Potential Side Effects of Florinef on Hypoadrenocorticism (HA)
The potential side effects of Florinef (fludrocortisone) on Hypoadrenocorticism (HA) include:
- Hypernatremia, hypokalemia, hyperglycemia, and congestive heart failure when used chronically 3
- Minimal side effects, as indicated by very low-certainty evidence in people with orthostatic hypotension due to diabetes or Parkinson disease 4
- Higher risk of all-cause hospitalizations compared to midodrine in patients with orthostatic hypotension, especially among those with congestive heart failure 5
Effects of Florinef on Orthostatic Hypotension
Florinef has been shown to:
- Increase blood volume and blood pressure in people with orthostatic hypotension 4
- Restore plasma volume and improve orthostatic tolerance in individuals undergoing head-down bedrest 6
- Not prevent orthostatic hypotension in astronauts after spaceflight, despite protecting plasma volume 7
Considerations for Treatment
When considering Florinef as a treatment for HA, it is essential to weigh the potential benefits against the possible side effects, particularly in patients with a history of congestive heart failure or other cardiovascular conditions 5. Additionally, the effectiveness of Florinef in preventing orthostatic hypotension may vary depending on the individual and the specific context, such as spaceflight 7 or head-down bedrest 6.