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Fludrocortisone


General


Pronunciation

(floo droe KOR ti sone)


Indications


Use: Labeled Indications

Addison disease: Partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison disease

Salt-losing adrenogenital syndrome: Treatment of salt-losing adrenogenital syndrome (congenital adrenal hyperplasia)


Contraindications


Hypersensitivity to fludrocortisone or any component of the formulation; systemic fungal infections

Documentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.


Dosing and Administration


Dosing: Adult

Addison disease: Oral: 0.1 mg daily; if transient hypertension develops, reduce dose to 0.05 mg daily; maintenance dosage range: 0.1 mg 3 times weekly to 0.2 mg daily. Preferred administration with cortisone or hydrocortisone.

Salt-losing adrenogenital syndrome (or congenital adrenal hyperplasia): Oral: 0.1 to 0.2 mg daily

The Endocrine Society recommends a maintenance dose range of 0.05 to 0.2 mg once daily (in combination with hydrocortisone) for patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (Speiser 2010).

Orthostatic hypotension (off-label use; Kearney 2009; Lahrmann 2006; Lanier 2011): Oral: Initial: 0.1 mg daily in conjunction with a high-salt diet and adequate fluid intake; may be increased in increments of 0.1 mg per week; maximum dose: 1 mg daily. Note: Doses exceeding 0.3 mg daily may not be beneficial and predispose patient to unwanted side effects (eg, hypertension, hypokalemia).


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Adrenal insufficiency, autoimmune (aldosterone deficiency component Addison disease); replacement therapy (off-label dosing): Limited data available: Oral: 0.05 to 0.2 mg daily (Betterle 2002; Kliegman 2011)

Congenital adrenal hyperplasia (salt losers) (eg, 21-hydroxylase deficiency) (off-label dosing): Limited data available: Note: Use in combination with glucocorticoid therapy (eg, hydrocortisone); concurrent sodium replacement therapy may be required, particularly in young infants. Oral:

Infants, Children, and Adolescents (actively growing): Usual range: 0.05 to 0.2 mg daily in 1 or 2 divided doses; doses as high as 0.3 mg/day may be necessary (AAP 2000; AAP 2010; Speiser 2010)

Adolescents (fully grown): 0.05 to 0.2 mg once daily (AAP 2010; Speiser 2010)


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturers labeling; use with caution.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling; use with caution.


Administration

Oral: Administer without regard to food; if GI upset, may take with food.


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.


Storage

Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F); avoid excessive heat. The Canadian labeling recommends to store at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as acetate:

Generic: 0.1 mg


Drug Interactions

Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy

Androgens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens. Monitor therapy

Antacids: May decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Management: No dose adjustment is needed for single 40 mg aprepitant doses. For other regimens, reduce oral dexamethasone or methylprednisolone doses by 50%, and IV methylprednisolone doses by 25%. Antiemetic regimens containing dexamethasone reflect this adjustment. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Monitor therapy

Calcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic). Monitor therapy

Ceritinib: Corticosteroids may enhance the hyperglycemic effect of Ceritinib. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Corticosteroids (Systemic). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Corticosteroids (Systemic). 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. 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. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Desirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

DiltiaZEM: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Consider therapy modification

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Indacaterol: May enhance the hypokalemic effect of Corticosteroids (Systemic). Monitor therapy

Indium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination

Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. 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. Consider therapy modification

Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

MiFEPRIStone: May diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (e.g., for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Avoid combination

Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. 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. Consider therapy modification

Nicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

NSAID (COX-2 Inhibitor): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Monitor therapy

NSAID (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (Nonselective). Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Quinolone Antibiotics: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolone Antibiotics. Specifically, the risk of tendonitis and tendon rupture may be increased. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

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. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Telaprevir: Corticosteroids (Systemic) may decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Corticosteroids (Systemic). Management: Concurrent use of telaprevir and systemic corticosteroids is not recommended. When possible, consider alternatives. If used together, employ extra caution and monitor closely for excessive corticosteroid effects and diminished telaprevir effects. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Urea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Monitor therapy


Monitoring Parameters

Blood pressure; blood glucose, electrolytes, weight; growth and development in children; HPA axis suppression.


Lab Test Interferences


Test Interactions

Corticosteroids may affect the nitrobluetetrazollum test for bacterial infection and produce false-negative results.


Adverse Reactions


Frequency not defined.

Cardiovascular: Cardiac failure, cardiomegaly, edema, hypertension

Central nervous system: Delirium, depression, emotional lability, euphoria, hallucination, headache, increased intracranial pressure, insomnia, malaise, nervousness, personality changes, pseudotumor cerebri, psychiatric disturbance, psychosis, seizure, vertigo

Dermatologic: Acne vulgaris, atrophic striae, diaphoresis, erythema, hyperpigmentation, maculopapular rash, skin atrophy, skin rash, suppression of skin test reaction, urticaria

Endocrine & metabolic: Cushing 's syndrome, diabetes mellitus, glycosuria, growth suppression, hirsutism, HPA-axis suppression, hyperglycemia, hypokalemia, hypokalemic alkalosis, impaired glucose tolerance, menstrual disease, negative nitrogen balance, subcutaneous fat atrophy

Gastrointestinal: Abdominal distention, esophageal ulcer, pancreatitis, peptic ulcer

Hematologic & oncologic: Bruise, petechia, purpura

Hypersensitivity: Anaphylaxis (generalized)

Neuromuscular & skeletal: Amyotrophy, bone fracture, myasthenia, myopathy, osteonecrosis (femoral and humeral heads), osteoporosis, vertebral compression fracture

Ophthalmic: Cataract, exophthalmos, glaucoma, increased intraocular pressure

Miscellaneous: Wound healing impairment


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.

- Anaphylactoid reactions: Rare cases of anaphylactoid reactions have been observed in patients receiving corticosteroids.

- Immunosuppression: Prolonged use may increase risk of infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to killed or inactivated vaccines. Exposure to chickenpox or measles should be avoided. Corticosteroids should not be used for cerebral malaria or viral hepatitis. Close observation is required in patients with latent tuberculosis (TB) and/or TB reactivity. Restrict use in active TB (only fulminating or disseminated TB in conjunction with antituberculosis treatment). Amebiasis should be ruled out in any patient with recent travel to tropic climates or unexplained diarrhea prior to initiation of corticosteroids. Use with extreme caution in patients with Strongyloides infections; hyperinfection, dissemination and fatalities have occurred.

- Kaposi sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered (Goedert 2002).

- Myopathy: Acute myopathy has been reported with high-dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.

- Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression to psychotic manifestation. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

Disease-related concerns:

- Cardiovascular disease: Use with caution in patients with HF and/or hypertension; use may be associated with fluid retention, electrolyte disturbances, and hypertension. Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.

- Diabetes: Use corticosteroids with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

- Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, ulcerative colitis, abscess or other pyogenic infection) due to perforation risk.

- Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.

- Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.

- Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Use with caution in patients with a history of ocular herpes simplex; corneal perforation has occurred; do not use in active ocular herpes simplex. Consider routine eye exams in chronic users.

- 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.

- Seizure disorders: Use corticosteroids with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.

- Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Elderly: Because of the risk of adverse effects, use with caution in the elderly with the smallest possible effective dose for the shortest duration.

- Pediatric: May affect growth velocity; growth and development should be routinely monitored in pediatric patients.

Other warnings/precautions:

- Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.

- Stress: Patients may require higher doses when subject to stress (ie, trauma, surgery, severe illness).


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 (Park-Wyllie, 2000; Pradat, 2003). Systemic corticosteroids may also influence fetal growth (decreased birth weight); however, information is conflicting (Lunghi, 2010). Hypoadrenalism may occur in newborns following maternal use of corticosteroids in pregnancy; monitor.

When systemic corticosteroids are needed in pregnancy, it is generally recommended to use the lowest effective dose for the shortest duration of time, avoiding high doses during the first trimester (Leachman, 2006; Lunghi, 2010). Fludrocortisone may be used to treat women during pregnancy who require therapy for congenital adrenal hyperplasia (Speiser, 2010).


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Pharmacology

Very potent mineralocorticoid with high glucocorticoid activity; used primarily for its mineralocorticoid effects. Promotes increased reabsorption of sodium and loss of potassium from renal distal tubules.


Metabolism

Hepatic


Half-Life Elimination

Plasma: ≥3.5 hours; Biological: 18 to 36 hours


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, insomnia, or agitation. Have patient report immediately to prescriber signs of infection, signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of Cushing 's disease (weight gain in upper back or stomach; moon face; severe headache; or slow healing), signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of skin changes (pimples, stretch marks, slow healing, or hair growth), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), severe loss of strength and energy, irritability, tremors, tachycardia, confusion, sweating a lot, dizziness, shortness of breath, excessive weight gain, swelling of arms or legs, angina, menstrual irregularities, bone pain, joint pain, vision changes, behavioral changes, depression, seizures, burning or numbness feeling, bruising, bleeding, severe abdominal pain, black, tarry, or bloody stools, or vomiting blood (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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