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Pronunciation
(floo droe KOR ti sone)
Generic Available (U.S.)
Yes
Index Terms
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease; treatment of salt-losing adrenogenital syndrome
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted with fludrocortisone; adverse events have been observed with corticosteroids in animal reproduction studies. Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts; adverse events in the fetus/neonate have been noted in case reports following large doses of systemic corticosteroids during pregnancy.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Corticosteroids are excreted in human milk; information specific to fludrocortisone has not been located.
Contraindications
Hypersensitivity to fludrocortisone or any component of the formulation; systemic fungal infections
Warnings/Precautions
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Fludrocortisone is primarily a mineralocorticoid agonist, but may also inhibit the HPA axis.
• Immunosuppression: May increase risk of infection and/or limit response to vaccinations; close observation is required in patients with latent tuberculosis and/or TB reactivity. Restrict use in active TB (only in conjunction with antituberculosis treatment).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with HF; use may be associated with fluid retention, edema, weight gain and hypertension.
• Electrolyte disturbances: Use with caution in patients with sodium retention and potassium loss. Monitor electrolytes periodically; sodium restriction and/or potassium supplementation may be required.
• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.
• Myocardial infarction (MI): Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.
• Osteoporosis: Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.
• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.
Special populations:
• Elderly: Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly in the smallest possible effective dose for the shortest duration.
Other warnings/precautions:
• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.
Adverse Reactions
Frequency not defined.
Cardiovascular: CHF, edema, hypertension
Central nervous system: Dizziness, headache, seizures
Dermatologic: Acne, bruising, rash
Endocrine & metabolic: HPA suppression, hyperglycemia, hypokalemic alkalosis, suppression of growth
Gastrointestinal: Peptic ulcer
Neuromuscular & skeletal: Muscle weakness
Ocular: Cataracts
Miscellaneous: Anaphylaxis (generalized), diaphoresis
Drug Interactions
Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Risk X: Avoid combination
Aminoglutethimide: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Antacids: May decrease the bioavailability of Corticosteroids (Oral). Risk D: Consider therapy modification
Antidiabetic Agents: Corticosteroids (Systemic) may diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification
Barbiturates: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapy
Calcitriol: Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Corticosteroids (Systemic). Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
Deferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Risk D: Consider therapy modification
Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Risk C: Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Corticosteroids (Systemic). Exceptions: Azithromycin; Azithromycin (Systemic); Spiramycin. Risk D: Consider therapy modification
Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Risk D: Consider therapy modification
NSAID (COX-2 Inhibitor): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Risk C: Monitor therapy
NSAID (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (Nonselective). Risk C: Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Primidone: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Quinolone Antibiotics: May enhance the adverse/toxic effect of Corticosteroids (Systemic). Risk of tendon-related side effects, including tendonitis and rupture, may be enhanced. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Thiazide Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Risk D: Consider therapy modification
Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy
Mechanism of Action
Promotes increased reabsorption of sodium and loss of potassium from renal distal tubules
Pharmacodynamics/Kinetics
Absorption: Rapid and complete
Protein binding: 42%
Metabolism: Hepatic
Half-life elimination, plasma: 30-35 minutes; Biological: 18-36 hours
Time to peak, serum: ∼1.7 hours
Dosage
Oral:
Infants and Children: 0.05-0.1 mg/day
Adults: 0.1-0.2 mg/day with ranges of 0.1 mg 3 times/week to 0.2 mg/day
Addison's disease: Initial: 0.1 mg/day; if transient hypertension develops, reduce the dose to 0.05 mg/day. Preferred administration with cortisone (10-37.5 mg/day) or hydrocortisone (10-30 mg/day).
Salt-losing adrenogenital syndrome: 0.1-0.2 mg/day
Administration: Oral
Administration in conjunction with a glucocorticoid is preferable.
Monitoring Parameters
Monitor blood pressure and signs of edema when patient is on chronic therapy; very potent mineralocorticoid with high glucocorticoid activity; monitor serum electrolytes, serum renin activity, blood pressure, and growth in children; monitor for evidence of infection; stop treatment if a significant increase in weight or blood pressure, edema, or cardiac enlargement occurs
Dietary Considerations
Systemic use of mineralocorticoids/corticosteroids may require a diet with increased potassium, vitamins A, B6, C, D, folate, calcium, zinc, and phosphorus, and decreased sodium. With fludrocortisone, a decrease in dietary sodium is often not required as the increased retention of sodium is usually the desired therapeutic effect.
Patient Education
Take with or after meals. Take once-a-day dose with food in the morning. Limit intake of caffeine or stimulants. Maintain adequate nutrition; consult prescriber for possibility of special dietary recommendations. If you have diabetes, monitor serum glucose closely and notify prescriber of changes; this medication can alter glycemic response. Notify prescriber if you are experiencing higher than normal levels of stress; medication may need adjustment. Periodic ophthalmic examinations will be necessary. You will be susceptible to infection. You may experience insomnia or nervousness. Report weakness, change in menstrual pattern, vision changes, signs of hyperglycemia, signs of infection (eg, fever, chills, mouth sores, perianal itching, vaginal discharge), or worsening of condition.
Geriatric Considerations
The most common use of fludrocortisone in the elderly is orthostatic hypotension that is unresponsive to more conservative measures. Attempt nonpharmacologic measures (hydration, support stockings etc) before starting drug therapy.
Additional Information
In patients with salt-losing forms of congenital adrenogenital syndrome, use along with cortisone or hydrocortisone. Fludrocortisone 0.1 mg has sodium retention activity equal to DOCA® 1 mg.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: In patients with salt-losing forms of congenital adrenogenital syndrome, use along with cortisone or hydrocortisone. Fludrocortisone 0.1 mg has sodium retention activity equal to DOCA® 1 mg.
Evidence-Based Information:
Adrenal Insufficiency: Patients on long-term steroid supplementation will require higher corticosteroid doses when subject to stress (ie, trauma, surgery, severe infection). This agent has significant mineralocorticoid activity with consequent hemodynamic effects. Fludrocortisone has been used to treat severe orthostatic hypotension. Abrupt withdrawal may result in adrenal insufficiency with hypotension and hyperkalemia. Guidelines for glucocorticoid replacement during various surgical procedures have been published (Coursin, 2002; Salem, 1994).
Septic Shock: Annane, et al (2002) randomized 300 septic shock patients to either hydrocortisone (50 mg I.V. push every 6 hours) and fludrocortisone (50 mcg tablet daily via nasogastric tube) or matching placebos for 7 days. The mean Simplified Acute Physiology Score II (SAPS II) was 57 ± 19 in the placebo group and 60 ± 19 in the active treatment group. The Logistic Organ Dysfunction score was 9 ± 3 in the placebo group and 9 ± 3 in the active treatment group. In patients who did not appropriately respond to cosyntropin (nonresponders), there were significantly fewer deaths in the active treatment group. Vasopressor therapy was withdrawn more frequently in this subset of the active treatment group. Adverse events were similar in both groups.
In the CORTICUS trial (Sprung, 2008), 484 septic shock patients were randomized within 72 hours of onset to receive either hydrocortisone (50 mg I.V. push every 6 hours) or placebo for 5 days followed by a 6-day taper. The primary endpoint was 28-day mortality in patients who did not respond to cosyntropin. The SAPS II score in the treatment group was 49.5 ± 17.8 and 48.6 ± 16.7 in the placebo group. The Sequential Organ Failure Assessment scores were 10.6 ± 3.4 in the treatment group and 10.6 ± 3.2 in the placebo group. Different than the Annane study, in the patients who did not respond to cosyntropin, there was no mortality difference at 28 days; 39.2% (95% CI: 30.5-47.9) mortality in the hydrocortisone group and 36.1% (95% CI: 26.9-45.3, p=0.69) mortality in the placebo group. A trend towards increased incidence of superinfection was noted in hydrocortisone patients. New septic shock episodes, hyperglycemia, and hypernatremia were more frequent in the hydrocortisone group. Hydrocortisone did not improve survival in this population of septic shock patients regardless of corticotropin response.
The 2008 Surviving Sepsis Campaign Guidelines suggest the following: Intravenous hydrocortisone be given only to adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy (Grade 2C); ACTH stimulation test not be used to identify the subset of adults with septic shock who should receive hydrocortisone (Grade 2B); patients with septic shock should not receive dexamethasone if hydrocortisone is available (Grade 2B); the addition of fludrocortisone if hydrocortisone is not available and the steroid that is substituted does not have significant mineralocorticoid activity (Grade 2C); doses of corticosteroids comparable to >300 mg hydrocortisone daily not be used in severe sepsis or septic shock for the purpose of treating septic shock (Grade 1A). They also recommend corticosteroids not be administered for the treatment of sepsis in the absence of shock. There is, however, no contraindication to continuing maintenance steroid therapy or to using stress dose steroids if the patient's endocrine or corticosteroid administration history warrants (Grade 1D).
The 2008 Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients recommend a diagnosis of critical illness related corticosteroid insufficiency can be made by a delta cortisol level (after 250 mcg cosyntropin) of <9 mcg/dL or a random cortisol <10 mcg/dL (Grade 2B). However, they recommend against the use of ACTH stimulation test to determine if septic shock or ARDS patients should receive steroid therapy (Grade 2B). They recommend to consider using hydrocortisone in septic shock patients who have responded poorly to resuscitation and vasopressors (Grade 2B) and glucocorticoid treatment should be tapered slowly and not stopped abruptly (Grade 2B). Dexamethasone is not recommended for the treatment of septic shock or ARDS (Grade 1B). Fludrocortisone therapy is considered optional (Grade 2B).
Cardiovascular Considerations
Long-term steroid therapy is associated with fluid retention and hypertension. This agent has some mineralocorticoid activity with consequent hemodynamic effects. Fludrocortisone has been used to treat severe orthostatic hypotension. Patients will often have steroid-induced adverse effects on glucose tolerance and lipid profiles. In discontinuing steroid therapy in patients on long-term steroid supplementation, it is important that steroid therapy be discontinued gradually. Abrupt withdrawal may result in adrenal insufficiency with hypotension and hyperkalemia.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
Barbiturates and carbamazepine may decrease corticosteroid effects; useful in the management of psychotropic-induced hypotension
Nursing: Physical Assessment/Monitoring
Teach patients to report opportunistic infection and adrenal suppression. Instruct patients with diabetes to monitor serum glucose levels closely; corticosteroids can alter glycemic response. Dose may need to be increased if patient is experiencing higher than normal levels of stress. When discontinuing, taper dose and frequency slowly.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as acetate: 0.1 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Fludrocortisone Acetate)
0.1 mg (30): $24.99
References
Abraham E and Evans T, “Corticosteroids and Septic Shock (editorial),” JAMA, 2002, 288(7):886-7.
Annane D, Sebille V, Charpentier C, et al, “Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock,” JAMA, 2002, 288(7):862-71.
Coursin DB and Wood KE, “Corticosteroid Supplementation for Adrenal Insufficiency,” JAMA, 2002, 287(2):236-40.
Cooper MS and Stewart PM, “Corticosteroid Insufficiency in Acutely Ill Patients,” N Engl J Med, 2003, 348(8):727-34.
Dellinger RP, Levy MM, Carlet JM, et al, “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008,” [published correction appears in Crit Care Med, 2008, 36(4):1394-6], Crit Care Med, 2008, 36(1):296-327.
Hotchkiss RS and Karl IE, “The Pathophysiology and Treatment of Sepsis,” N Engl J Med, 2003, 348(2):138-50.
Marik PE, Pastores SM, Annane D, et al, “Recommendations for the Diagnosis and Management of Corticosteroid Insufficiency in Critically Ill Adult Patients: Consensus Statements From an International Task Force by the American College of Critical Care Medicine,” Crit Care Med, 2008, 36(6):1937-49.
Ostensen M, “Optimisation of Antirheumatic Drug Treatment in Pregnancy,” Clin Pharmacokinet, 1994, 27(6):486-503.
Pradat P, Robert-Gnansia E, Di Tanna GL, et al, “First Trimester Exposure to Corticosteroids and Oral Clefts,” Birth Defects Res A Clin Mol Teratol, 2003, 67(12):968-70.
Salem M, Tainsh RE Jr, Bromberg J, et al, “Perioperative Glucocorticoid Coverage. A Reassessment 42 Years After Emergence of a Problem,” Ann Surg, 1994, 219(4):416-25.
Sprung CL, Annane D, Keh D, et al, “Hydrocortisone Therapy for Patients With Septic Shock,” N Engl J Med, 2008, 358(2):111-24.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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