Drug Interactions between dexamethasone and fluconazole

The immunosuppressant and anti-inflammatory effects of corticosteroids, particularly at higher dosages, may reduce resistance to infectious agents, increase the risk of disseminated infections, mask symptoms of infection, and reactivate or exacerbate latent/resolved infections; fatal cases have been reported. Avoid use of corticosteroids in patients with cerebral malaria. Screen patients for active (or history of) infection with tuberculosis, hepatitis, varicella, measles, and amebiasis, especially prior to prolonged treatment. Closely monitor for reactivation of latent infections; chemoprophylaxis may be required. In general, corticosteroids should not be used in patients with active infections, especially systemic fungal infections, unless medically necessary to control drug reactions. However, for corticosteroid-dependent patients who develop a severe or life-threatening infection, continuation of corticosteroid therapy with at least physiologic replacement dosages should be considered, since these patients may have secondary adrenocortical insufficiency. Removal of external steroid during periods of stress may be detrimental to these patients.

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

The use of certain parenteral formulations of dexamethasone, hydrocortisone, methylprednisolone, prednisolone and triamcinolone is considered by the drug manufacturers to be contraindicated in neonates, particularly premature infants and infants of low birth weight. Some formulations of these drugs contain benzyl alcohol which, when used in bacteriostatic saline intravascular flush and endotracheal tube lavage solutions, has been associated with fatalities and severe respiratory and metabolic complications in low-birth-weight premature infants. However, many experts feel that, in the absence of benzyl alcohol-free equivalents, the amount of the preservative present in these formulations should not necessarily preclude their use if they are clearly indicated. The American Academy of Pediatrics considers benzyl alcohol in low doses (such as when used as a preservative in some medications) to be safe for newborns. Continuous infusions of high dosages of medications containing benzyl alcohol may, however, cause toxicity and should be avoided if possible.

Corticosteroids can raise blood glucose level by antagonizing the action and suppressing the secretion of insulin, which results in inhibition of peripheral glucose uptake and increased gluconeogenesis. Therapy with corticosteroids should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during corticosteroid therapy, and their antidiabetic regimen adjusted accordingly.

Corticosteroids mimic the effects of endogenous cortisol and aldosterone. Use of these agents may aggravate conditions of hyperadrenocorticalism in a dose-dependent manner.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Long-term therapy with corticosteroids should be administered cautiously in patients with a history of cataracts, glaucoma, or increased intraocular pressure.

Corticosteroids may have enhanced effects on patients with cirrhosis due to decreased metabolism of these agents. Patients with cirrhosis should be monitored more closely for excessive cortisol effects. Dosage adjustments may be required in these patients.

Corticosteroids may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Large doses of any corticosteroid can demonstrate these effects, particularly if given for longer periods. Therapy with corticosteroids should be administered cautiously in patients with preexisting fluid retention, hypertension, congestive heart failure, and/or renal dysfunction. Dietary sodium restriction and potassium supplementation may be advisable.

Corticosteroids may aggravate the symptoms of psychosis and emotional instability. Patients with these conditions should be monitored for increased or worsened symptoms during corticosteroid therapy.

Corticosteroids can raise blood glucose level by antagonizing the action and suppressing the secretion of insulin, which results in inhibition of peripheral glucose uptake and increased gluconeogenesis. Therapy with corticosteroids should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during corticosteroid therapy, and their antidiabetic regimen adjusted accordingly.

Corticosteroids may cause gastrointestinal perforation and hemorrhage, usually when given in high dosages or for prolonged periods. They may also mask symptoms of complications such as peritonitis or intraabdominal sepsis. Therapy with corticosteroids should be avoided or administered cautiously in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or recent intestinal anastomoses.

Corticosteroids can cause hypernatremia, hypokalemia, and fluid retention. These mineralocorticoid effects are most significant with fludrocortisone, followed by hydrocortisone and cortisone, then by prednisone and prednisolone. The remaining corticosteroids, betamethasone, dexamethasone, methylprednisolone, and triamcinolone, have little mineralocorticoid activities. However, large doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods. All corticosteroids also increase excretion of calcium and can cause hypocalcemia. Therapy with corticosteroids should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Corticosteroids may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Large doses of any corticosteroid can demonstrate these effects, particularly if given for longer periods. Therapy with corticosteroids should be administered cautiously in patients with preexisting fluid retention, hypertension, congestive heart failure, and/or renal dysfunction. Dietary sodium restriction and potassium supplementation may be advisable.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Long-term therapy with corticosteroids should be administered cautiously in patients with a history of cataracts, glaucoma, or increased intraocular pressure.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

Corticosteroids may cause peptic ulcer disease and gastrointestinal (GI) hemorrhage, usually when given in high dosages or for prolonged periods. However, even conventional dosages may aggravate symptoms in patients with a history of peptic ulcers. Delayed healing of ulcers has also been reported. Therapy with corticosteroids should be avoided or administered cautiously in patients with active or latent peptic ulcers or other risk factors for GI bleeding. Some clinicians recommend the use of prophylactic antacids or H2-antagonists between meals when large doses of corticosteroids are necessary.

Corticosteroids may increase blood coagulability and have rarely been associated with the development of intravascular thrombosis, thromboembolism, and thrombophlebitis. Therapy with corticosteroids should be administered cautiously in patients who have or may be predisposed to thrombotic or thromboembolic disorders.

In patients with latent tuberculosis or tuberculin reactivity, the use of pharmacologic dosages of corticosteroids may cause a reactivation of the disease. Close monitoring for signs and symptoms of tuberculosis is recommended if corticosteroid therapy is administered to patients with a history of tuberculosis or tuberculin reactivity. During prolonged corticosteroid therapy, tuberculosis chemoprophylaxis may be considered.

Corticosteroids mimic the effects of endogenous cortisol and aldosterone. Use of these agents may aggravate conditions of hyperadrenocorticalism in a dose-dependent manner.

Corticosteroids mimic the effects of endogenous cortisol and aldosterone. Use of these agents may aggravate conditions of hyperadrenocorticalism in a dose-dependent manner.

Corticosteroids may elevate serum triglyceride and LDL cholesterol levels if used for longer than brief periods. Patients with preexisting hyperlipidemia may require closer monitoring during prolonged corticosteroid therapy, and adjustments made accordingly in their lipid-lowering regimen.

Corticosteroids can cause hypernatremia, hypokalemia, and fluid retention. These mineralocorticoid effects are most significant with fludrocortisone, followed by hydrocortisone and cortisone, then by prednisone and prednisolone. The remaining corticosteroids, betamethasone, dexamethasone, methylprednisolone, and triamcinolone, have little mineralocorticoid activities. However, large doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods. All corticosteroids also increase excretion of calcium and can cause hypocalcemia. Therapy with corticosteroids should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Corticosteroids may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Large doses of any corticosteroid can demonstrate these effects, particularly if given for longer periods. Therapy with corticosteroids should be administered cautiously in patients with preexisting fluid retention, hypertension, congestive heart failure, and/or renal dysfunction. Dietary sodium restriction and potassium supplementation may be advisable.

Corticosteroids can cause hypernatremia, hypokalemia, and fluid retention. These mineralocorticoid effects are most significant with fludrocortisone, followed by hydrocortisone and cortisone, then by prednisone and prednisolone. The remaining corticosteroids, betamethasone, dexamethasone, methylprednisolone, and triamcinolone, have little mineralocorticoid activities. However, large doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods. All corticosteroids also increase excretion of calcium and can cause hypocalcemia. Therapy with corticosteroids should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Corticosteroids can cause hypernatremia, hypokalemia, and fluid retention. These mineralocorticoid effects are most significant with fludrocortisone, followed by hydrocortisone and cortisone, then by prednisone and prednisolone. The remaining corticosteroids, betamethasone, dexamethasone, methylprednisolone, and triamcinolone, have little mineralocorticoid activities. However, large doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods. All corticosteroids also increase excretion of calcium and can cause hypocalcemia. Therapy with corticosteroids should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Corticosteroids may have enhanced effects in hypothyroidism due to decreased metabolism of these agents. Patients with hypothyroidism should be monitored more closely for excessive cortisol effects. Dosage adjustments may be required secondary to changes in their thyroid condition.

Corticosteroids may cause gastrointestinal perforation and hemorrhage, usually when given in high dosages or for prolonged periods. They may also mask symptoms of complications such as peritonitis or intraabdominal sepsis. Therapy with corticosteroids should be avoided or administered cautiously in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or recent intestinal anastomoses.

Corticosteroids are primarily metabolized by the liver and may have enhanced effects in patients with liver disease. Dosage adjustments may be necessary in these patients.

Although corticosteroids are commonly used in the treatment of myasthenia gravis to increase muscle strength, these agents should nevertheless be administered with caution in such setting. Patients should be treated in an intensive care unit and receive respiratory support, since muscle strength may markedly decrease initially, particularly with high dosages. Preferably, therapy should begin with relatively low dosages (15 to 25 mg/day of prednisone or equivalent) and be increased stepwise as tolerated (approximately 5 mg/day of prednisone or equivalent at 2- to 3-day intervals until marked clinical improvement or a dosage of 50 mg/day is reached). Improvement may be delayed and gradual. Thus, it is important not to discontinue therapy prematurely.

The use of corticosteroids may be associated with left ventricular free-wall rupture in patients who have had a recent myocardial infarction. Pharmacologic dosages of corticosteroids should be administered with great caution in such patients.

Toxic myopathy has been observed with the chronic use or the administration of large doses of corticosteroids, often in patients with disorders of neuromuscular transmission such as myasthenia gravis or in patients receiving neuromuscular blocking agents. Fluorinated corticosteroids such as betamethasone, dexamethasone, and triamcinolone appear to cause more severe muscle atrophy and weakness than the nonfluorinated agents. Moreover, multiple-daily doses are more toxic than once-daily or, preferably, alternate-day morning doses. Steroid myopathy is generalized and sometimes accompanied by respiratory weakness and dyspnea. In some cases, it has resulted in quadriparesis. Elevations of creatine kinase (CK) may also occur, albeit infrequently. After withdrawal of corticosteroid therapy, recovery may be slow and incomplete. Therapy with corticosteroids should be administered cautiously in patients with preexisting myopathy or myoneural disorders since these conditions may confound the diagnosis of steroid-induced myopathy. The presence of a normal serum CK level, minimal/no changes of myopathy on electromyography, and type 2 muscle fiber atrophy on biopsy are helpful in suggesting steroid-induced weakness. If steroid myopathy is suspected, a dosage reduction or discontinuation of the steroid should be considered.

Toxic myopathy has been observed with the chronic use or the administration of large doses of corticosteroids, often in patients with disorders of neuromuscular transmission such as myasthenia gravis or in patients receiving neuromuscular blocking agents. Fluorinated corticosteroids such as betamethasone, dexamethasone, and triamcinolone appear to cause more severe muscle atrophy and weakness than the nonfluorinated agents. Moreover, multiple-daily doses are more toxic than once-daily or, preferably, alternate-day morning doses. Steroid myopathy is generalized and sometimes accompanied by respiratory weakness and dyspnea. In some cases, it has resulted in quadriparesis. Elevations of creatine kinase (CK) may also occur, albeit infrequently. After withdrawal of corticosteroid therapy, recovery may be slow and incomplete. Therapy with corticosteroids should be administered cautiously in patients with preexisting myopathy or myoneural disorders since these conditions may confound the diagnosis of steroid-induced myopathy. The presence of a normal serum CK level, minimal/no changes of myopathy on electromyography, and type 2 muscle fiber atrophy on biopsy are helpful in suggesting steroid-induced weakness. If steroid myopathy is suspected, a dosage reduction or discontinuation of the steroid should be considered.

Pharmacologic dosages of corticosteroids should be used cautiously in patients with ocular herpes simplex because of the risk of corneal perforation. Corticosteroids are not recommended for patients with active ocular herpes simplex.

Corticosteroids reduce osteoblastic function and inhibit the absorption of intestinal calcium, which can result in bone resorption and bone loss during prolonged therapy. In addition, bone matrix may be affected by the protein-catabolic effects of corticosteroids, especially when given in high dosages or for prolonged periods, leading to aseptic necrosis and fractures. Long-term or high-dose corticosteroid therapy should be administered cautiously and only if necessary in patients with or at risk for osteoporosis. Adverse skeletal effects may be minimized by alternate-day or intermittent administration. Any patient receiving prolonged therapy with the equivalent of 7.5 mg prednisone/day or more are at risk for glucocorticoid-induced osteoporosis and should be managed according to The American College of Rheumatology (ACR) guidelines.

Corticosteroids may cause peptic ulcer disease and gastrointestinal (GI) hemorrhage, usually when given in high dosages or for prolonged periods. However, even conventional dosages may aggravate symptoms in patients with a history of peptic ulcers. Delayed healing of ulcers has also been reported. Therapy with corticosteroids should be avoided or administered cautiously in patients with active or latent peptic ulcers or other risk factors for GI bleeding. Some clinicians recommend the use of prophylactic antacids or H2-antagonists between meals when large doses of corticosteroids are necessary.

The use of corticosteroids may be associated with left ventricular free-wall rupture in patients who have had a recent myocardial infarction. Pharmacologic dosages of corticosteroids should be administered with great caution in such patients.

Corticosteroids may aggravate the symptoms of psychosis and emotional instability. Patients with these conditions should be monitored for increased or worsened symptoms during corticosteroid therapy.

Corticosteroids may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Large doses of any corticosteroid can demonstrate these effects, particularly if given for longer periods. Therapy with corticosteroids should be administered cautiously in patients with preexisting fluid retention, hypertension, congestive heart failure, and/or renal dysfunction. Dietary sodium restriction and potassium supplementation may be advisable.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

Corticosteroids can cause hypernatremia, hypokalemia, and fluid retention. These mineralocorticoid effects are most significant with fludrocortisone, followed by hydrocortisone and cortisone, then by prednisone and prednisolone. The remaining corticosteroids, betamethasone, dexamethasone, methylprednisolone, and triamcinolone, have little mineralocorticoid activities. However, large doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods. All corticosteroids also increase excretion of calcium and can cause hypocalcemia. Therapy with corticosteroids should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Unlike most helminths, Strongyloides stercoralis has the ability to replicate in the human host. In patients with strongyloidiasis, the use of pharmacologic or immunosuppressive dosages of corticosteroids may result in Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. Therapy with corticosteroids should be administered with extreme caution, if at all, in these patients. For patients on corticosteroids who develop known or suspected Strongyloides infestation, withdrawal of corticosteroids or reduction of the dose of corticosteroids is recommended.

In patients with scleroderma, corticosteroids may precipitate renal crisis with malignant hypertension, possibly via steroid-induced increases in renin substrate and angiotensin II levels and decreases in vasodilator prostaglandin production. Renal failure may ensue. Therapy with corticosteroids should be administered cautiously in patients with scleroderma. In addition, they should be limited to short-term use.

Corticosteroids may increase blood coagulability and have rarely been associated with the development of intravascular thrombosis, thromboembolism, and thrombophlebitis. Therapy with corticosteroids should be administered cautiously in patients who have or may be predisposed to thrombotic or thromboembolic disorders.

In patients with latent tuberculosis or tuberculin reactivity, the use of pharmacologic dosages of corticosteroids may cause a reactivation of the disease. Close monitoring for signs and symptoms of tuberculosis is recommended if corticosteroid therapy is administered to patients with a history of tuberculosis or tuberculin reactivity. During prolonged corticosteroid therapy, tuberculosis chemoprophylaxis may be considered.

Corticosteroids may cause gastrointestinal perforation and hemorrhage, usually when given in high dosages or for prolonged periods. They may also mask symptoms of complications such as peritonitis or intraabdominal sepsis. Therapy with corticosteroids should be avoided or administered cautiously in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or recent intestinal anastomoses.