What are the guidelines for using Florinef (fludrocortisone) in treating orthostatic hypotension?

Fludrocortisone for Orthostatic Hypotension

Recommended Dosing and Initiation

Start fludrocortisone at 0.05-0.1 mg once daily in the morning, titrating up to 0.1-0.3 mg daily based on clinical response, with a maximum dose of 1.0 mg daily if needed. 1

• The initial dose should be 0.05-0.1 mg taken as a single morning dose upon awakening 1
• Individual titration to 0.1-0.3 mg daily is typically sufficient for most patients 1
• An alternative loading approach uses 0.2 mg initially followed by 0.1 mg daily maintenance 1
• Higher doses up to 500 µg (0.5 mg) daily may be required in children, younger adults, or during the last trimester of pregnancy when progesterone counteracts mineralocorticoid effects 2
• The medication should be kept refrigerated per formulation instructions, though actual decay is only 0.1% in the first 6 months at room temperature 2

Mechanism of Action and Clinical Effects

Fludrocortisone works through two primary mechanisms: sodium retention and direct vessel wall effects 1

• It expands body fluid volume, though preliminary data suggest this volume is allocated to the perivascular space rather than intravascular space 3
• Treatment limits the orthostatic decrease in cardiac output, which is the primary mechanism for blood pressure improvement 3
• The drug increases upright arterial pressure by reducing the excessive postural drop in cardiac output seen in neurogenic orthostatic hypotension 3
• In one study, standing systolic pressure improved from 83 mmHg to 114 mmHg with combined fludrocortisone and head-up sleeping 3

Position in Treatment Algorithm

Fludrocortisone is recommended as a first-line pharmacological option alongside midodrine and droxidopa when non-pharmacological measures fail to adequately control symptoms. 1

• Non-pharmacological measures should be implemented first: increase fluid intake to 2-3 liters daily and salt consumption to 6-9g daily (if not contraindicated), elevate head of bed 10 degrees, use compression garments, teach physical counter-maneuvers (leg crossing, squatting, muscle tensing), and recommend smaller more frequent meals 1
• The American College of Cardiology gives fludrocortisone a Class IIb recommendation (might be reasonable) for recurrent vasovagal syncope with inadequate response to salt and fluid intake 2
• The European Society of Cardiology also gives it a Class IIb recommendation (may be considered) for young patients with orthostatic vasovagal syncope, low-normal blood pressure, and no contraindications 2
• For non-responders to monotherapy, consider combination therapy with midodrine and fludrocortisone 1

Critical Monitoring Requirements

Monitor for supine hypertension (the most important limiting factor), hypokalemia, peripheral edema, and congestive heart failure. 1

• Supine hypertension is the most significant adverse effect and primary dose-limiting factor 1
• Check electrolytes periodically due to mineralocorticoid effects causing potassium wasting 1
• Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes and monitor for supine hypertension 1, 4
• Regular monitoring should assess for peripheral edema and signs of fluid overload 1
• The therapeutic goal is minimizing postural symptoms rather than restoring normotension 1

Absolute Contraindications

Do not use fludrocortisone in patients with active heart failure, significant cardiac dysfunction, severe renal disease where sodium retention would be harmful, or pre-existing supine hypertension. 1

• Active congestive heart failure is an absolute contraindication due to sodium and fluid retention effects 1
• Severe renal disease where additional sodium retention would be harmful contraindicates use 1
• Pre-existing supine hypertension should preclude fludrocortisone therapy 1

Drug Interactions to Avoid

Several medications must be avoided or require dose adjustments when using fludrocortisone 2

• Avoid completely: Diuretics, acetazolamide, carbenoxolone, liquorice, and NSAIDs 2
• Drospirenone-containing contraceptives may require increased fludrocortisone dosing 2
• Liquorice and grapefruit juice potentiate mineralocorticoid effects and should be avoided 2

Special Clinical Contexts

Primary Adrenal Insufficiency

• Daily dose of 50-200 µg is usually sufficient in primary adrenal insufficiency 2
• Patients should eat sodium salt and salty foods without restriction and avoid potassium-containing salts 2
• Mineralocorticoid replacement is evaluated by asking about salt cravings or lightheadedness, measuring supine and standing blood pressure, and checking for peripheral edema 2
• Under-replacement is common and sometimes compensated for by glucocorticoid over-replacement, potentially predisposing to recurrent adrenal crises 2

Levodopa-Induced Orthostatic Hypotension

• Doses of 0.05-0.2 mg daily effectively treat severe orthostatic symptoms secondary to levodopa therapy 5
• Treatment allows maintenance of optimal antiparkinsonian levodopa doses that would otherwise need reduction 5

Evidence Quality and Limitations

The evidence for fludrocortisone is limited to very low-certainty evidence from small, short-term trials, yet it remains guideline-recommended based on clinical experience and physiologic rationale. 6

• A Cochrane review found only three small crossover RCTs (total 28 participants) with 2-3 week durations 6
• Studies only examined fludrocortisone in diabetes and Parkinson disease populations 6
• Despite limited RCT evidence, observational data from 341 patients with familial dysautonomia suggests long-term use may not be harmful 6
• The drug has been used safely for 6-10 months in parkinsonian patients without adverse reactions 5

Practical Implementation Points

• Avoid taking medications that worsen orthostatic hypotension after 6 PM to prevent supine hypertension during sleep (this applies more to midodrine, but timing considerations are relevant for overall management) 1
• Essential hypertension in patients with primary adrenal insufficiency should be treated by adding a vasodilator, not by stopping mineralocorticoid replacement, though dose reduction should be considered 2
• Reassess patients within 1-2 weeks after initiating or changing fludrocortisone dose 1
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension 1