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Fludrocortisone (Acetate) See Introduction

PharmacoKinetics Oral absorption of Fludrocortisone (Acetate) is found to be 97% ±2. Plasma protien binding is 75%. Presystemic metabolism is noted to be 90% and metabolism is reported Hepatic. Renal Excretion accounts for 80% and plasma half life is 0.5hr.

Fludrocortisone (Systemic)
VA CLASSIFICATION Primary: HS052 Secondary: CV900; DX900 Commonly used brand name(s): Florinef. Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Category:

Corticosteroid (mineralocorticoid)— antihypotensive (idiopathic orthostatic)— diagnostic aid (renal tubular acidosis)— Indications Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling. Accepted Note: Because of its marked effect of sodium retention, the use of fludrocortisone acetate in the treatment of conditions other then those indicated herein is not advised {59} Adrenocortical insufficiency, chronic primary (treatment) or Adrenocortical insufficiency, chronic secondary (treatment)—Fludrocortisone is indicated as partial replacement therapy in the treatment of adrenocortical insufficiency in Addison's disease{59} . {02} {10} {13} {17} {24} {26} {29} {34} {35} {36} {45} Adrenogenital syndrome, congenital (treatment)— Fludrocortisone is indicated in salt-losing forms of adrenogenital syndrome. {02} {10} {25} {26} {29} {40}

Effectiveness of fludrocortisone therapy indicates that the condition is caused by hyporeninemic hypoaldosteronism rather than by renal tubular transport dysfunction. corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. {10} {23} {25} {40} Mineralocorticoids act on the distal tubules to increase potassium excretion. it is used only for its mineralocorticoid effects. but to a lesser extent. {02} {10} {17} {29} Cation transport in other secretory cells is similarly affected. Half-life: ³3. bind to DNA (chromatin). Biotransformation: Hepatic. {10} Duration of action: . {10} excretion of water and electrolytes by the large intestine and by salivary and sweat glands is also altered.49 {07} {12} Mechanism of action/Effect: Fludrocortisone acetate is an adrenal cortical steroid that has very high levels of mineralocorticoid activity and moderate levels of glucocorticoid activity. in renal tubular disorders (diagnosis and treatment)]1—Fludrocortisone is used in the treatment of Type IV renal tubular acidosis associated with hyporeninemic hypoaldosteronism. and stimulate transcription of mRNA (messenger RNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for the physiological effects of these hormones. idiopathic orthostatic (treatment)]1—Fludrocortisone is used in conjunction with increased sodium intake in the treatment of idiopathic orthostatic hypotension.[Hypotension. {39} {40} [Acidosis. {10} {23} {29} {40} However. renal. {10} Protein binding: High. At the cellular level.5 hours (plasma). {01} {10} 18–36 hours (biological). and sodium reabsorption and subsequent water retention. {39} {40} Fludrocortisone is also used as an aid in diagnosing the cause of the condition. Pharmacology/Pharmacokinetics Physicochemical characteristics: Molecular weight— 422. These complexes then enter the cell nucleus. {25} 1 Not included in Canadian product labeling. hydrogen ion excretion.

{17} However. Precautions to Consider Carcinogenicity/Mutagenicity Adequate animal studies have not been conducted on the carcinogenicity or mutagenicity of fludrocortisone. {03} {10} {29} Breast-feeding Problems in humans have not been documented. One published report described the use of fludrocortisone in the treatment of severe hyponatremia that occurred following head injury in 3 geriatric patients in whom syndrome of inappropriate antidiuretic hormone (SIADH) had been ruled out as the cause of the hyponatremia. {10} Pregnancy/Reproduction Pregnancy— Studies on use of fludrocortisone during pregnancy have not been done in humans.1–2 days. many corticosteroids have been shown to be teratogenic in laboratory animals at low doses. However. {03} {10} {29} Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely observed for signs of hypoadrenalism. {10} {17} {23} {32} {33} Geriatrics Appropriate studies have not been performed in the geriatric population. corticosteroids are distributed into breast milk and may cause unwanted effects in the infant such as growth suppression and inhibition of endogenous steroid production. Elimination: Renal.4 mg of fludrocortisone per day. {10} {23} {17} {29} Adequate studies on use of fludrocortisone during pregnancy have not been done in animals. mostly as inactive metabolites. {02} {10} {23} Pediatrics Although adequate and well-controlled studies have not been done in the pediatric population. {42} {56} Drug interactions and/or related problems . corticosteroids may cause unwanted effects in children and growing adolescents. Teratogenicity of these agents in humans has not been demonstrated{59}{03} {10} {29} FDA Pregnancy Category C.1 to 0. such as growth suppression and inhibition of endogenous steroid production. {42} {56} {57} Doses ranged from 0.

rarely salicylate toxicity may occur in patients who discontinue steroids after concurrent high-dose aspirin therapy. adjustment in salicylate dose may be required {59}) » Digitalis glycosides {10} {56} {57} (risk of cardiac arrhythmias or digitalis toxicity associated with hypokalemia may be increased. increased antidiabetic dose may be necessary {59}) Aspirin {59} ( increased ulcerogenic effect. adjustment of anticoagulant dose may be required{59}) Antidiabetic drugs {59} ( diminished antidiabetic effect.The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance): Note: Combinations containing any of the following medications. when estrogen therapy is initiated. {10} {57} serum potassium concentrations and cardiac function should be monitored. depending on the amount present. {53} {56} increased fludrocortisone dose and dietary sodium . oral {59} ( decreased prothrombin time response. via induction of P-450 liver enzymes. may also interact with this medication. {58} Anabolic steroids {59} ( enhanced tendency toward edema {59}) Anticoagulants. monitor for symptoms of hyperglycemia. lithium antagonized the mineralocorticoid effects of fludrocortisone. an increase {61}{62} in corticosteroid dosage may be required {59}) » Hepatic enzyme inducers {10} {40} {41} {43} {44} {52} {56} (See Appendix II ) (phenytoin and rifampin have been reported to increase 6-beta-hydroxylation of fludrocortisone. {40} {41} {43} {44} {52} {56} fludrocortisone dosage increase may be required {10} {23} {40} {41} {43} {44} {52} {56}) » Hypokalemia-causing medications {10} {40} {41} {46} {47} {48} {49} {56} (See Appendix II ) (risk of severe hypokalemia due to other hypokalemia-causing medications may be increased. {10} {57} potassium supplements may be required {10} {57} ) Estrogen {59} ( increased levels of corticosteroid-binding globulin. monitor prothrombin levels. monitor salicylate levels or the therapeutic effect for which aspirin is given. {10} {40} {41} {56} monitoring of serum potassium concentrations and cardiac function and potassium supplementation may be required {10} {17} {23} {40} {41} {51} {56}) Lithium {53} {56} (in one published case report. thereby increasing the bound (inactive) fraction. decreased pharmacologic effect of aspirin.

supplementation were required during concurrent use {53} {56}) » Sodium-containing medications or foods {56} (concurrent use with fludrocortisone in the treatment of Type IV renal tubular acidosis may result in hypernatremia. edema. and potentially severe increases in blood pressure. {56} adjustment of sodium intake may be required {02} {10} {17} {23} {56}) Vaccines {59} ( neurological complications and lack of antibody response {59}) Laboratory value alterations The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance): With physiology/laboratory test values Blood pressure (may be increased {10} {17} {23} {26} {29} {40} {42} {45}) (may be decreased due to increased blood volume {10} {17} {23} {42}) Hematocrit percentage Nitroblue tetrazolium test {59} ( may show false-negative results {59}) ( may be decreased {59}) Prothrombin time response Potassium {42} ) (serum concentration may be decreased due to increased potassium excretion {29} Sodium (serum concentration may be increased due to sodium retention {02} {10} {17} {23} {26} {29} {42} ) Medical considerations/Contraindications The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance). Risk-benefit should be considered when the following medical problems exist » Cardiac disease {02} or » Congestive heart failure {17} {29} or » Hypertension {02} {10} {17} {23} {29} or Peripheral edema or .

» Renal function impairment. metastatic carcinoma.and fluid-retaining effects detrimental to these patients {10} {17} {23} ) Diverticulitis {59} Glomerulonephritis. depending on condition. » = major clinical significance): Blood pressure determinations and Serum electrolyte concentrations {29} (recommended at onset of therapy and at periodic . except when fludrocortisone is used to treat Type IV renal tubular acidosis {10} {29} (sodium. convulsive disorders. acute {17} {29} Hepatic function impairment {10} {17} {23} {29} or Hypothyroidism {10} {17} {23} {29} (clearance of fludrocortisone may be decreased) Herpes simplex. active or latent {59} Sensitivity to fludrocortisone Tuberculosis. chronic {17} {29} Osteoporosis {10} (may be exacerbated by increased calcium excretion {17} {29} {37}) Peptic ulcer. thromboembolitic tendencies. vaccinia and varicella {60} Patient monitoring The following may be especially important in patient monitoring (other tests may be warranted in some patients. ocular {59} ( possible corneal perforation {59}) Hyperthyroidism {10} {23} (clearance of fludrocortisone may be increased) Hypoprothrombinemia {59} ( use aspirin cautiously in conjunction with corticosteroids {59}) Intestinal anastomoses. exanthema. Cushing's syndrome. active or latent (suppression of immune system could cause overwhelming infection {59}) Ulcerative colitis. unspecific {59} ( use corticosteroids with caution if there is a probability of impending perforation. thrombophlebitis. abscess or other pyogenic infection {59}) Note: Canadian product information also lists the following medical conditions/contraindications for which risk-benefit should be considered if the medical problem exists: antibiotic resistant infections. diabetes mellitus. fresh {59} Myasthenia gravis {59} Nephritis.

however these effects should be kept in mind. dilated neck veins. generalized {02}{17}{29}{59}(cough. difficulty swallowing . shortness of breath. neck. face. wheezing )— mineralocorticoid effect: see note above{59} convulsions {59} cushingoid state. Drug-Interaction. the glucocorticoid side effects are not usually a problem. extreme fatigue. and trunk) exophthalmos {59}(eyeballs bulge out of eye sockets) . feet. particularly when fludrocortisone is used over a prolonged period of time or in conjunction with cortisone or a similar glucocorticoid. When fludrocortisone is used in the small dosages recommended. walking with a limp ) cardiac enlargement —mineralocorticoid effect: see note above{59} congestive heart failure {59}(chest pain. swelling of face. {59} Those indicating need for medical attention Incidence less frequent or rare Aggravating or masking of infections {59} anaphylaxis. or lower legs. and eyelids) aseptic necrosis of femoral and humeral heads {59}{62} (decreased range of motion. tightness in chest. redness of conjunctivae. irregular breathing. weight gain.JustAnswer. redness and itching of skin. troubled breathing. swelling of nasal membranes. irregular heartbeat. joint pain. development of {59}(increased fat deposits on face. decreased urine output.com Side/Adverse Effects The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive: Note: Most adverse reactions of fludrocortisone are caused by the drug's mineralocorticoid activity (retention of sodium and water). fingers. shortness of breath. hives.intervals during prolonged therapy {10} {17}) Ads by Google Ask: Drug Interaction Pharmacists Will Answer in Minutes! Questions Answered Every 9 Seconds.

tearing of eyes) glycosuria {59} growth suppression —in children{59} hyperglycemia {59} hypertension {59}(blurred vision. or trunk . stomachache. loss of consciousness. fruit-like breath odor. blurred vision. decreased vision. dry skin. muscle cramps or pain. pounding in the ears. increased {59} latent diabetes mellitus manifestations {59}(blurred vision. severe weakness in arms. hallucinations. severe or continuing. increased hunger. dry mouth. nervousness. agitation or combativeness. headache. increased thirst. skin rash. unusual weight loss) negative nitrogen balance — due to protein catabolism{59} oral hypoglycemic agents. nausea. sweating. flushed. increased —usually after treatment{59} intraocular pressure. vomiting) mental disturbances. troubled breathing. increased requirements {59}(patients taking oral hypoglycemic agents for diabetes may need to increase the amount they take) osteoporosis {59}( back or rib pain. decrease in height) . nausea.facial erythema {59}(redness of face) glaucoma {59}(blindness. coughing. vomiting)— mineralocorticoid effect: see note above insulin requirements. eye pain. unexplained weight loss. slow or fast heartbeat)—mineralocorticoid effect: see note above hypokalemic syndrome {02}{10}{17}{23}{26}{38}{40}{59}(irregular heartbeat. fatigue. coughing up blood. depression. unusual tiredness. pain in joints or muscles. legs. dizziness. expressed fear of impending death) necrotizing angiitis {59}(chills. increased urination. confusion. increased {59}( patients taking insulin for diabetes may need to increase the amount they take) intracranial pressure with papilledema. shortness of breath. loss of appetite. loss of appetite. headache. nausea or vomiting. headache. severe {59}(anxiety.

unusually fast heartbeat palpitations) thrombophlebitis {59}( changes in skin color. fever. swelling of foot or leg) ulcerative esophagitis {59}(chest pain. vomiting. swelling of feet or lower legs)—mineralocorticoid effect: see note above{59} posterior subcapsular cataracts {59} potassium loss — mineralocorticoid effect: see note above{59} secondary adrenocortical and pituitary unresponsiveness —particularly in times of stress{59} spontaneous fractures {59}(fractures in arms or legs without any injury) subcutaneous fat atrophy {59} suppressed reactions to skin tests {59} syncopal episodes {59}(fainting or lightheadedness when getting up from a lying or sitting position. side. pains in stomach. pimples) .pancreatitis {59}(bloating. full or bloated feeling or pressure in the stomach) acneiform eruptions {59}(acne. possibly radiating to the back. abdominal or stomach pain or burning) peripheral edema {02}{10}{17}{23}{25}{26}{29}{37}{45}{59}(rapid weight gain. loss of appetite. impaired {59}(problems with would healing ) Those indicating need for medical attention only if they continue or are bothersome Incidence less frequent or rare abdominal distention {59}(swelling of abdominal or stomach area. darkened urine. pain. fast heartbeat. constipation. yellow eyes or skin) pathologic fracture of long bones {59} peptic ulcer with possible perforation and hemorrhage {59}(bloody or black. chills. tarry stools. heartburn ) vertebral compression fractures {59}(fractures in the neck or back) wound healing. or abdomen. tenderness. nausea. indigestion.

trunk. unable to sleep) loss of muscle mass {59} maculopapular rash {59}(redness or discoloration of skin) menstrual irregularities {59}(menstrual changes) muscle weakness {59} petechiae purpura {59}(small red or purple spots on skin) striae {59}(reddish purple lines on arms. decreased {59} dizziness {10}{23}{37}{59} ecchymoses {59}( bruising. redness of skin. or groin) steroid myopathy {59} sweating. severe or continuing {02}{10}{17}{23}{45}{59} hirsutism {59}(unusual increase in hair growth) hives {59} hyperpigmentation of skin and nails {59}(change in color of skin or nails) insomnia {59}(sleeplessness. flat. itching. increased {59} thin. blue or purplish patches in the skin) headache. skin rash) . legs. fragile skin {59} urticaria {59}(hives or welts. large. trouble sleeping.allergic skin rash {59} bruising {59} carbohydrate tolerance. face.

not doubling doses {10} {23} » Proper dosing » Proper storage Precautions while using this medication » Regular visits to physician to check progress during therapy Carrying medical identification card during long-term therapy . especially: Sensitivity to fludrocortisone Pregnancy—Infants born to mothers who received substantial doses of corticosteroids during pregnancy require close observation for signs of hypoadrenalism Use in children and growing adolescents—May cause growth suppression and inhibition of endogenous steroid production Breast-feeding— Corticosteroids are found in the breast milk of lactating women receiving systemic therapy with these agents. refer to Advice for the Patient. especially hypokalemia-causing medications. or renal function impairment Proper use of this medication » Importance of not taking more medication than the amount prescribed Missed dose: Taking as soon as possible. congestive heart failure. consider emphasizing the following selected information (» = major clinical significance): Before using this medication » Conditions affecting use. especially cardiac disease. hypertension. or sodium-containing medications or food Other medical problems.Patient Consultation As an aid to patient consultation. digitalis glycosides. not taking if almost time for next dose. Fludrocortisone (Systemic) In providing consultation. Caution should be exercised when fludrocortisone acetate is administered to a nursing woman Other medications. hepatic enzyme inducers.

increased intracranial pressure with papilledema. hypertension hypokalemic syndrome. Oral Dosage Forms Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U. development of cushingoid state. glaucoma. aseptic necrosis of femoral and humeral heads. peptic ulcer with possible perforation and hemorrhage. {35} {36} {40} {45} Sodium supplementation may also be necessary. fludrocortisone should be administered with appropriate glucocorticoid therapy such as 10 to 30 mg of hydrocortisone per day or 10 to 37. glycosuria. exophthalmos. peripheral edema. negative nitrogen balance. especially aggravating or masking of infections. posterior subcapsular cataracts. impaired wound healing General Dosing Information When used in the treatment of adrenocortical insufficiency or salt-losing forms of adrenogenital syndrome. spontaneous fractures. increased requirements for oral hypoglycemic agents. especially chickenpox and measles.5 mg of cortisone per day. {02} {10} {23} {29} {36} {40} {45} In the treatment of Type IV renal tubular acidosis. syncopal episodes. pathologic fracture of long bones. especially in patients with hypertension. or renal function impairment. potassium loss. product labeling. concurrent use of a diuretic may be necessary to decrease the risk of sodium and fluid retention. osteoporosis. convulsions. congestive heart failure. subcutaneous fat atrophy. generalized anaphylaxis. increased intraocular pressure. Use of glucocorticoids{63} in immunosuppressant doses is associated with a higher risk of infection. {59} Care should be taken in adults and children to avoid exposure to viral infections. vertebral compression fractures. secondary adrenocortical and pituitary unresponsiveness. if the patient has not already had the disease or been immunized against it. with the potential for those infections to be of a more serious nature.S. If exposed.Side/adverse effects Signs of potential side effects. pancreatitis. {62}cardiac enlargement. facial erythema. congestive heart failure. FLUDROCORTISONE ACETATE TABLETS USP . growth suppression. thrombophlebitis. latent diabetes mellitus manifestations.increased insulin requirements. suppressed reactions to skin tests. ulcerative esophagitis. hyperglycemia. therapy with varicella zoster immune globulin or pooled intravenous immunoglobulin may be a consideration{59} . severe mental disturbances.

{10} {17} {23} {25} {29} {34} {40} {45} Adrenogenital syndrome.1 mg) (Rx) [Florinef (scored) (lactose)]{10}{23} Canada— 100 mcg (0.1 mg) per day. {10} {13} {17} {23} {25} {29} {35} {36} {40} {45} Note: Dose should be reduced to 50 mcg (0. {16} {22} {40} Strength(s) usually available U.2 mg) once a day have been employed.1 to 0. preferably between 15 and 30 °C (59 and 86 °F).1 mg) per day. 100 mcg (0.2 mg) per day. .05 to 0. chronic Oral.05 mg) per day if transient hypertension occurs. congenital Oral.Usual adult and adolescent dose Adrenocortical insufficiency. {10} {17} {23} {25} {29} {40} [Antihypotensive. 50 to 100 mcg (0.2 mg) per day.— 100 mcg (0. {10} {17} {23} {25} {29} {36} {40} Dosages of 100 mcg (0. 100 to 200 mcg (0. 50 to 200 mcg (0. {10} {23} unless otherwise specified by manufacturer. idiopathic orthostatic]1 Oral.1 mg) three times a week to 200 mcg (0.S. Store in a well-closed container. Usual pediatric dose Oral.1 mg) (Rx) [Florinef (scored) (lactose)]{17}{29} Packaging and storage: Store below 40 °C (104 °F).05 to 0.