Fludrocortisone Side Effects
Fludrocortisone's most clinically significant adverse effects stem from its mineralocorticoid activity and include hypertension, edema, hypokalemia, and cardiac complications, with particular concern for poor tolerability in elderly patients. 1
Primary Mineralocorticoid-Related Side Effects
The FDA label clearly delineates that most adverse reactions result from sodium and water retention 1:
- Cardiovascular complications: Hypertension, edema, cardiac enlargement, and congestive heart failure are the most common and clinically significant adverse effects 1
- Electrolyte disturbances: Hypokalemia and hypokalemic alkalosis occur frequently, with hypokalemia developing in approximately 24% of patients at a mean of 8 months of treatment 2
- Potassium loss: This is a direct consequence of the mineralocorticoid effect and may require supplementation 3
Age-Related Tolerability Concerns
Elderly patients demonstrate particularly poor long-term tolerance to fludrocortisone, even at low doses 2:
- In patients over 65 years, 33% discontinued treatment at a mean of 5 months 2
- Specific reasons for discontinuation in the elderly included hypertension (5 patients), cardiac failure (4 patients), depression (3 patients), and edema (3 patients) 2
- Blood pressure effects may be more pronounced in older adults and those prone to polypharmacy effects 3
Glucocorticoid-Related Side Effects
When used chronically or at higher doses, glucocorticoid effects can emerge 1:
- Musculoskeletal: Muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, and pathologic fractures 1
- Gastrointestinal: Peptic ulcer with possible perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis 1
- Dermatologic: Impaired wound healing, thin fragile skin, bruising, petechiae, facial erythema, increased sweating, subcutaneous fat atrophy, purpura, striae, hyperpigmentation, hirsutism, and acneiform eruptions 1
- Neurological: Convulsions, increased intracranial pressure with papilledema, vertigo, headache, and severe mental disturbances 1
- Endocrine: Menstrual irregularities, cushingoid state development, growth suppression in children, secondary adrenocortical and pituitary unresponsiveness, decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, and increased insulin requirements 1
- Ophthalmic: Posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos 1
- Metabolic: Hyperglycemia, glycosuria, and negative nitrogen balance due to protein catabolism 1
Additional Adverse Reactions
- Allergic reactions: Allergic skin rash, maculopapular rash, and urticaria 1
- Other: Necrotizing angiitis, thrombophlebitis, aggravation or masking of infections, insomnia, syncopal episodes, and anaphylactoid reactions 1
Critical Monitoring Parameters
Regular monitoring is essential when adding fludrocortisone to regimens that include ACE inhibitors or ARBs 4:
- Serum creatinine and potassium levels require regular monitoring due to increased hyperkalemia risk when combined with renin-angiotensin system blockers 4
- Electrolyte levels, particularly sodium and potassium, should be checked if clinically indicated 5
Drug Interactions and Dietary Considerations
- Several medications interact with fludrocortisone, including diuretics, acetazolamide, carbenoxolone, and NSAIDs 3
- Liquorice and grapefruit juice potentiate the mineralocorticoid effect and should be avoided 3
- Patients should be advised to consume sodium salt and salty foods without restriction, while avoiding potassium-containing salts 3
Clinical Pitfall
The standard doses of 0.05-0.1 mg daily may actually represent undertreatment in many patients with Addison's disease, as most patients require 0.2 mg to maintain adequate sodium and water balance 6. However, this higher dosing increases the risk of adverse effects, particularly in elderly populations where even low doses are poorly tolerated 2.