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]

Because of the high sodium-retaining activity of fludrocortisone, the drug should be used with extreme caution in patients with Addison's disease, cardiac disease, congestive heart failure, hypertension, hepatic disease, or renal disease. Therapy should be discontinued if significant weight gain, cardiac enlargement, blood pressure increase, or edema occurs. If fludrocortisone-induced edema develops, dietary sodium should be restricted because a high sodium intake can enhance sodium retention and potassium loss. Potassium supplements should be administered as necessary.

Corticosteroid therapy, like fludrocortisone, has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction and should therefore be undertaken cautiously in these patients.

Corticosteroids, like fludrocortisone, are well known to cause cataracts during long-term administration. Patients receiving corticosteroids chronically should be periodically assessed for cataract formation.

As with other corticosteroids, the use of fludrocortisone may be of concern in patients with selected infection. The manufacturers state that fludrocortisone is contraindicated in patients with systemic fungal infection. Corticosteroids should not be administered to patients with systemic infections unless appropriate chemotherapy is administered simultaneously. For example, the use of fludrocortisone in patients with active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary, as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Consider immune globulin administration and other appropriate therapy if patients taking prolonged fludrocortisone therapy alone or in conjunction with another glucocorticoid are exposed to either chicken pox (varicella) or measles, as these diseases can have a more serious or even fatal course in patients on immunosuppressant corticosteroids.

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. The usual precautions include patients with coagulopathy, Cushing's syndrome, diabetes mellitus, diverticulitis, emotional instability, GI disease, hepatic disease, herpes infection, hypothyroidism, infection, intestinal anastomosis (because of the possibility of perforation), myasthenia gravis, osteoporosis, psychosis, renal disease, seizure disorder, and ulcerative colitis.[29890]

Increased dosages of rapid-acting corticosteroids may be necessary for patients undergoing physiologic stress such as major surgery, acute infection, or blood loss. The corticosteroid, like fludrocortisone, should be administered before, during, and after the stressful situation.

Safety and effectiveness of fludrocortisone in infants or children have not been established, but the drug has been used off-label for certain pediatric patients (see Dosage). Children who receive prolonged therapy with fludrocortisone should be carefully observed. Corticosteroids can retard bone growth. Children receiving corticosteroids may also be immunosuppressed and thus, more susceptible to infection. Normally innocuous infections can become fatal in these children, so care should be taken to avoid exposure to these diseases.

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.[29890]

Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to fludrocortisone should not receive any form of fludrocortisone. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. 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]

Fludrocortisone tablets may contain lactose; patients with lactase deficiency should take appropriate precautions with use.

Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of steroids. Killed or inactivated vaccines may be administered, however, the response to such vaccines can not be predicted. Corticosteroid therapy like fludrocortisone usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (less than 2 weeks); low to moderate dose; or maintenance physiologic doses (replacement therapy). In general, patients with severe immunosuppression due to large doses of corticosteroids should not receive vaccination with live-virus vaccines. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for 2 weeks or longer, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.[12498] [43236]

Use fludrocortisone cautiously in geriatric patients. At doses typically used for mineralocorticoid effects, fludrocortisone has no substantial glucocorticoid activity. However, precautions relating to the use of glucocorticoids should be observed in all patients receiving fludrocortisone either long-term or in conjunction with another glucocorticoid. Geriatric patients may commonly have conditions that may be exacerbated by fludrocortisone therapy such as hypertension, edema, hypokalemia, congestive heart failure, cataracts, glaucoma, increased intraocular pressure, renal insufficiency, and osteoporosis. Geriatric patients may also commonly be taking concomitant drug therapy that may interact with fludrocortisone.[29890] 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]