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Fludrocortisone
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Usual dose: 0.1 mg PO once daily, as a supplement to hydrocortisone or cortisone. Dosage may range from 0.1 mg PO 3 times per week to 0.2 mg PO once daily. Reduce the dose to 0.05 mg PO once daily if transient hypertension due to therapy develops. Max usual maintenance dosage: 0.2 mg/day. Dosage depends on disease severity and patient response. Close monitoring is to detect the possible need for dosage adjustment such as remissions or exacerbations of the disease and stressors like surgery, infection, or trauma.[49507]
0.05 mg to 0.3 mg per day PO, given in 1 to 2 divided doses, as a supplement to hydrocortisone or cortisone. Usual maintenance range per guidelines: 0.05 mg to 0.2 mg per day.[54122] [54123]
0.05 to 0.3 mg/day PO, given in 1 to 2 divided doses, as a supplement to hydrocortisone or cortisone. Usual maintenance range per guidelines: 0.05 to 0.2 mg per day. During the neonatal period and infancy, all classic congenital adrenal hyperplasia (CAH) patients should be treated with fludrocortisone in addition to hydrocortisone or cortisone. In those with salt-wasting CAH, the sodium content of breast milk or infant formulas is insufficient, and sodium chloride supplements [1 to 2 grams/day (17 to 34 mEq/day) in infancy] are necessary as well.[54122] [54123]
0.05 or 0.1 mg PO once daily, initially. Usual dose: 0.05 to 0.2 mg/day.[32679] [32680] [66385] [68047] [68048] [68049]
0.1 mg PO 3 times daily or 0.2 mg PO twice daily for up to 12 days.[58117] [68526] [68527] [68528]
Maintenance therapy usual max: 0.2 mg/day PO.
Maintenance therapy usual max: 0.2 mg/day PO.
Safety and efficacy have not been established, but doses of up to 0.3 mg/day PO have been used.
Safety and efficacy have not been established, but doses of up to 0.3 mg/day PO have been used.
Safety and efficacy have not been established, but doses of up to 0.3 mg/day PO have been used.
Safety and efficacy have not been established, but doses of up to 0.3 mg/day PO have been used.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
† Off-label indication
Fludrocortisone is an oral synthetic adrenocortical steroid derived from the substitution of a 9alpha-fluoride on the B ring of hydrocortisone. Fluorination at this position gives rise to potent mineralocorticoid activity. Pharmacologic actions are similar to those of aldosterone, an endogenous mineralocorticoid. The sodium-retaining activity of fludrocortisone is extremely high compared with other adrenocorticoids such as hydrocortisone. Although fludrocortisone has significant glucocorticoid activity, it has no appreciable glucocorticoid effects at usual therapeutic doses. Fludrocortisone is used as mineralocorticoid replacement therapy in patients with adrenocortical insufficiency and salt-losing adrenogenital syndrome. Fludrocortisone was approved by the FDA in 1954.
For storage information, see the specific product information within the How Supplied section.
May be administered without regard to meals; however, administer with meals to minimize GI upset.
Fludrocortisone has potent mineralocorticoid properties and as a result, most adverse reactions are due to its mineralocorticoid activity. These adverse effects include fluid imbalance, electrolyte imbalance (particularly hypokalemia), edema, congestive heart failure, cardiomegaly, and hypertension. A fludrocortisone dosage adjustment is recommended if hypertension develops during fludrocortisone therapy in combination with a glucocorticoid for Addison's disease. Hypertension, weight gain, edema, hypokalemia, heart size increase, sinus tachycardia, and suppressed plasma renin activity are clinical signs of overdosage with mineralocorticoids. If the above signs are noted, discontinue fludrocortisone. The symptoms will usually subside within several days; use a reduced fludrocortisone dose for subsequent treatment. To help prevent overdosage, regularly monitor blood pressure and serum electrolytes. A hypokalemic metabolic alkalosis syndrome can also be associated with fludrocortisone therapy and includes nausea and vomiting, orthostatic hypotension, QT prolongation, ST-T wave changes, severe weakness of the extremities, anorexia, and muscle cramps and pain.[49507]
Corticosteroids, like fludrocortisone, have been reported to cause pseudotumor cerebri (increased intracranial pressure) causing papilledema, oculomotor or abducens nerve paralysis, loss of vision, and headache.
Glucocorticoid side effects of fludrocortisone may occur when the drug is used over a prolonged period of time or in conjunction with a glucocorticoid. Corticosteroid therapy, including fludrocortisone, can mask the symptoms of infection and should be avoided during an acute viral, fungal, or bacterial infection. Neutropenia including febrile neutropenia has been reported by recipients of corticosteroids. Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods also may be at risk. Corticosteroids can reactivate tuberculosis and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately. Monitoring systemic corticosteroid recipients for signs of an opportunistic fungal infection is recommended, as cases of oropharyngeal candidiasis have been reported. Development of Kaposi's sarcoma has also been associated with prolonged administration of corticosteroids. Discontinuation of the corticosteroid may result in clinical improvement.[43319]
Glucocorticoid side effects of fludrocortisone may occur when the drug is used over a prolonged period of time or in conjunction with a glucocorticoid. Ocular effects such as corneal perforation, exophthalmos, posterior subcapsular cataracts, retinopathy, or ocular hypertension, can result from prolonged use of glucocorticoids and could result in glaucoma or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment, including blurred vision and blindness, has been reported with glucocorticoid administration by several routes of administration. Secondary fungal and viral infections of the eye (ocular infection) can be exacerbated by corticosteroid therapy.[49507]
Since fludrocortisone acetate is a potent mineralocorticoid compared to other corticosteroids, both the dosage
and the patient's salt intake should be carefully monitored in order to avoid the development of hypertension, edema or weight gain. Periodic monitoring of serum electrolyte concentrations is advised during prolonged therapy; dietary salt restriction and potassium supplementation may be necessary. Because of the high sodium-retaining activity of fludrocortisone and potential for edema and other related effects, the drug should be used with extreme caution in patients with cardiomyopathy, significant cardiac disease, congestive heart failure, hypertension, or renal disease/insufficiency.[49507]
People who have demonstrated a prior hypersensitivity reaction to fludrocortisone should not receive the drug. While the manufacturer states that corticosteroids are contraindicated in patients with known hypersensitivity to these agents [49507], true corticosteroid hypersensitivity and cross-reactivity among steroids is rare. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.[27616] [27642]
The lowest possible dose of fludrocortisone should be used to control the condition being treated. A gradual reduction in dosage should be made when possible. Adverse reactions to corticosteroids may be produced by too rapid withdrawal (abrupt discontinuation) or by continued use of large doses. To avoid drug-induced adrenal insufficiency, supportive dosage of corticosteroids may be required in times of stress (such as trauma, surgery, or severe illness) both during treatment with fludrocortisone acetate and for a year afterwards. At doses typically used for mineralocorticoid effects, fludrocortisone has no appreciable glucocorticoid activity. Glucocorticoid therapy is usually administered concomitantly with fludrocortisone therapy in treating adrenal insufficiency or salt-losing adrenogenital syndrome. Long term therapy or concomitant use with other glucocorticoids may, however, result in significant glucocorticoid effects. Cautions relating to the use of glucocorticoids should be observed in all patients receiving fludrocortisone either long term or in conjunction with another glucocorticoid.[49507]
Systemic corticosteroids, such as fludrocortisone, may cause immunosuppression and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: 1) Reduce resistance to new infections, 2) Exacerbate existing infections, 3) Increase the risk of disseminated infections, 4) Increase the risk of reactivation or exacerbation of latent infections 5) Mask some signs of infection. Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider corticosteroid withdrawal or dosage reduction as needed. If fludrocortisone is used to treat a condition in patients with latent tuberculosis (TB) or tuberculin reactivity, reactivation of TB may occur. Closely monitor such patients for TB reactivation. During prolonged fludrocortisone therapy, patients with latent TB or tuberculin reactivity should receive chemoprophylaxis. Viral infection, such as varicella zoster (chickenpox or shingles) and measles can have a serious or even fatal course in non-immune patients taking corticosteroids; other herpes infection (herpes simplex) may also disseminate in immunosuppressed individuals. Corticosteroids should be used with caution, if at all, in patients with ocular herpes simplex. In corticosteroid-treated patients who have not had these diseases or are nonimmune, avoid exposure of these people to these viral infections. If a corticosteroid-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If varicella develops, consider treatment with antiviral. If a corticosteroid-treated patient is exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. Hepatitis B exacerbation/reactivation can occur in patients who are hepatitis B virus carriers treated with immunosuppressive dosages of corticosteroids. Reactivation can also occur infrequently in corticosteroid-treated people who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with systemic corticosteroids. For individuals who show evidence of hepatitis B infection, consult providers with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Systemic fludrocortisone use is contraindicated in the presence of a systemic fungal infection. If a fungal infection develops during chronic corticosteroid therapy, corticosteroid withdrawal or dosage reduction is recommended. Corticosteroids, including fludrocortisone, may activate latent amebiasis. Latent or active amebiasis should be ruled out before initiating fludrocortisone in people who have spent time in the tropics or have unexplained diarrhea. Corticosteroids, including fludrocortisone, should be used with great care in the presence of known or suspected Strongyloides (threadworm) helminth infection. Corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. In selected patients from strongyloidiasis endemic areas who need systemic corticosteroids, consider administering prophylactic treatment. Also avoid corticosteroids, including fludrocortisone, in people with cerebral malaria.[49507]
Prolonged use of corticosteroids such as fludrocortisone may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infection due to bacteria, fungi or viruses.[49507]
Systemic corticosteroids, such as fludrocortisone, may decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus. There is an enhanced effect of corticosteroids in people with hypothyroidism.[49507]
Systemic corticosteroid use may be associated with neuro-psychiatric effects ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychosis. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Inform patients or caregivers of the potential for mood and behavioral changes with systemic fludrocortisone treatment and encourage them to seek medical attention if such symptoms develop.[49507]
Use fludrocortisone with caution in myasthenia gravis. An acute myopathy has been observed with the use of high doses of other systemic corticosteroids, most often occurring in people with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in those receiving concomitant therapy with neuromuscular blocking drugs. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.[49507]
Monitor growth and weight in pediatric patients receiving fludrocortisone. Chronic corticosteroid therapy, such as fludrocortisone, may cause growth inhibition in pediatric patients; linear growth retardation and delayed weight gain have been reported with systemic corticosteroid therapy in pediatric patients. Because bone development is critical in pediatric patients, monitor patients receiving high-dose or chronic corticosteroid treatment. Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (e.g., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead the development of osteopenia and osteoporosis at any age.[49507]
Corticosteroids like fludrocortisone should be used with caution in patients with nonspecific ulcerative colitis if there is a probability of impending GI perforation, abscess, or other pyogenic infection. Corticosteroids should also be used cautiously in patients with diverticulitis, fresh intestinal anastomoses, or active or latent peptic ulcer disease.[49507]
Patients with severe hepatic disease, such as cirrhosis, can have an exaggerated response to systemic corticosteroids, such as fludrocortisone.[49507]
Patients should not be vaccinated against smallpox or other live or live attenuated vaccines while taking fludrocortisone therapy. Other vaccination procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response.[49507] Follow expert recommendations regarding vaccination in immunosuppressed individuals.[43236]
According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium and should be avoided in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. The Beers expert panel recommends that fludrocortisone be prescribed in the lowest effective dose and for the shortest possible duration consistent with the needs of the patient.[63923]
Fludrocortisone is classified as FDA pregnancy risk category C.[49507] Studies involving use of fludrocortisone in pregnancy have not been done in humans. Complications, including cleft palate, still birth, and premature abortion, have been reported when corticosteroids were administered during pregnancy. Fludrocortisone acetate should be given to a pregnant woman only if clearly needed. If these drugs must be used during pregnancy, the potential risks should be discussed with the patient. The mother may require additional monitoring to ensure adequate replacement during pregnancy; insufficient treatment of Addison's disease during pregnancy is associated with fetal risks. The usual treatments for Addison's disease are usually continued throughout pregnancy and post-partum, and the mother may require dosage adjustments for proper replacement post-partum as requirements return to pre-pregnancy levels. Infants born to mothers who have taken substantial doses of corticosteroids during pregnancy should be monitored for signs of hypoadrenalism. In addition, maternal treatment with corticosteroids should be carefully documented in the infant's medical records to assist in follow-up.[49507]
Corticosteroids distribute into breast milk. Because of the risk of hypoadrenalism in the infant, or other potential adverse effects, fludrocortisone should be used cautiously during breast-feeding.[49507]
Endogenous corticosteroids are secreted by the adrenal cortex; their effects are believed to be due to modification of enzymatic activity rather than to a direct hormone-induced action. Fludrocortisone mimics the actions of aldosterone, an endogenous mineralocorticoid. Mineralocorticoids facilitate sodium resorption and promote hydrogen ion and potassium excretion at the level of the distal renal tubule. Small oral doses produce marked sodium retention and increased urinary potassium excretion. Among 5 adults with orthostatic hypotension who took fludrocortisone 0.3—1 mg/day for 10—14 days, the change in sodium balance ranged from +149 mmol to +282 mmol, and the change in plasma volume ranged from 185 ml to 299 mL. The mean recumbent blood pressure increased from 110 +/-6 over 69 +/-3 mmHg to 124 +/-7 over 79 +/-2 mmHg. Although fludrocortisone receipt tended to decrease the signs and symptoms of severe orthostatic hypotension, only incomplete symptomatic relief was obtained in each patient.[32776] Larger doses can inhibit endogenous adrenal cortical secretion, thymic activity, and pituitary corticotropin excretion; promote the deposition of liver glycogen; and, if protein intake is inadequate, induce negative nitrogen balance.
Fludrocortisone receipt (0.2—1 mg/day) for at least a year led to recumbent and standing blood pressure increases in all 7 adults with severe orthostatic hypotension; 5 had idiopathic disease and 2 had orthostatic hypotension associated with diabetes. Average systolic blood pressure values were at least 20 mmHg higher and average diastolic blood pressure values were at least 10 mmHg higher as compared with values before fludrocortisone receipt. Hypertensive retinopathy developed in 2 patients; one of the 2 patients also had x-ray evidence of cardiomegaly and electrocardiographic changes consistent with left ventricular hypertrophy. Although plasma volume increased over the first 10 days of fludrocortisone receipt, the plasma volume decreased to control levels despite further blood pressure increases. Treatment did not affect plasma catecholamines concentrations and did not enhance pressor response to infused norepinephrine in 5 patients who had hyperreactive blood pressure responses to norepinephrine before fludrocortisone receipt. An enhanced pressor response to infused norepinephrine occurred in 2 patients who showed normal blood pressure responses to norepinephrine before fludrocortisone receipt. Hemodynamic data were obtained from 2 patients; hypertension in the recumbent position was related to increases in total peripheral vascular resistance - no appreciable change in either cardiac output or plasma volume was noted.[32776]
Revision Date: 10/17/2024, 02:30:00 AMFludrocortisone is administered orally. The circulating drug binds extensively to the plasma proteins albumin and transcortin, and only the unbound portion of a dose is active. Systemic fludrocortisone is quickly distributed into the kidneys, intestines, skin, liver, and muscle. Fludrocortisone distributes into breast milk and crosses the placenta. Fludrocortisone is metabolized by the liver to inactive metabolites. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The biological half-life of fludrocortisone is 18—36 hours.
Fludrocortisone is absorbed rapidly from the GI tract. Peak plasma concentrations are reached within 1.5 hours.
Fludrocortisone is classified as FDA pregnancy risk category C.[49507] Studies involving use of fludrocortisone in pregnancy have not been done in humans. Complications, including cleft palate, still birth, and premature abortion, have been reported when corticosteroids were administered during pregnancy. Fludrocortisone acetate should be given to a pregnant woman only if clearly needed. If these drugs must be used during pregnancy, the potential risks should be discussed with the patient. The mother may require additional monitoring to ensure adequate replacement during pregnancy; insufficient treatment of Addison's disease during pregnancy is associated with fetal risks. The usual treatments for Addison's disease are usually continued throughout pregnancy and post-partum, and the mother may require dosage adjustments for proper replacement post-partum as requirements return to pre-pregnancy levels. Infants born to mothers who have taken substantial doses of corticosteroids during pregnancy should be monitored for signs of hypoadrenalism. In addition, maternal treatment with corticosteroids should be carefully documented in the infant's medical records to assist in follow-up.[49507]
Corticosteroids distribute into breast milk. Because of the risk of hypoadrenalism in the infant, or other potential adverse effects, fludrocortisone should be used cautiously during breast-feeding.[49507]
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