Prednisolone ODT

• Aminoglutethimide: Aminoglutethimide may lead to loss of corticosteroid-induced adrenal suppression.
• Amphotericin B: There have been cases reported in which concomitant use of Amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see also Potassium depleting agents).
• Anticholinesterase agents: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.
• Anticoagulant agents: Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.
• Antidiabetic Agents: Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.
• Antitubercular drugs: Serum concentrations of isoniazid may be decreased.
• CYP 3A4 inducers (e.g. barbiturates, phenytoin, carbamazepine, and rifampin): Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of prednisolone and require that the dosage of Prednisolone Sodium Phosphate be increased.
• CYP 3A4 inhibitors (e.g., ketoconazole, macrolide antibiotics): Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects.
• Cholestyramine: Cholestyramine may increase the clearance of corticosteroids.
• Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.
• Digitalis: Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.
• Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids thereby increasing their effect.
• NSAIDS, including aspirin and salicylates: Concomitant use of aspirin or other non-steroidal anti-inflammatory agents and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

• Potassium-depleting agents (e.g., diuretics, Amphotericin B): When corticosteroids are administered concomitantly with potassium-depleting agents, patients should be observed closely for development of hypokalemia.

• Skin Tests: Corticosteroids may suppress reactions to skin tests.
• Toxoids and live or inactivated Vaccines: Due to inhibition of antibody response, patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines.

Prednisolone Sodium Phosphate Orally Disintegrating Tablets are a sodium salt of the phosphoester of the glucocorticoid prednisolone. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract.

Prednisolone sodium phosphate occurs as white or slightly yellow, friable granules or powder. It is freely soluble in water; soluble in methanol; slightly soluble in alcohol and in chloroform; and very slightly soluble in acetone and in dioxane.

The chemical name of prednisolone sodium phosphate is pregna-1, 4-diene-3, 20-dione, 11, 17-dihydroxy-21-(phosphonooxy)-, disodium salt, (11ß)-. The empirical formula is C21H27Na2O8P; the molecular weight is 484.39. Its chemical structure is:

Each orally disintegrating tablet also contains the following inactive ingredients: citric acid, colloidal silicon dioxide, crospovidone, grape flavor, hypromellose, magnesium stearate, mannitol, methacrylate copolymer, microcrystalline cellulose, sodium bicarbonate, sucralose, and sucrose.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Prednisolone Sodium Phosphate was not formally evaluated in carcinogenicity studies. Review of the published literature identified the potential for malignancy at doses within the therapeutic range. In a 2-year study, male Sprague-Dawley rats administered prednisolone in drinking water at an estimated continuous daily prednisolone consumption of 368 mcg/kg/day (equivalent to 3.5 mg/day in a 60 kg individual based on an mg/m2 body surface area comparison) developed increased incidences of hepatic adenomas. However infrequent administration of prednisolone did not result in malignancy. In an 18-month study, intermittent (1, 2, 4.5 or 9 times per month) oral gavage of 3 mg/kg prednisolone did not induce tumors in female Sprague-Dawley rats (equivalent to 29 mg in a 60 kg individual based on a mg/m2 body surface area comparison).

Prednisolone Sodium Phosphate was not formally evaluated for genotoxicity. However, in published studies prednisolone was not mutagenic with or without metabolic activation in the Ames bacterial reverse mutation assay using Salmonella typhimurium and Escherichia coli, or in a mammalian cell gene mutation assay using mouse lymphoma L5178Y cells, according to current evaluation standards. In a published chromosomal aberration study in Chinese Hamster Lung (CHL) cells, a slight increase was seen in the incidence of structural chromosomal aberrations with metabolic activation at the highest concentration tested, however, the effect appears to be equivocal.

Prednisolone Sodium Phosphate was not formally evaluated in fertility studies. However, alterations in motility and numbers of spermatozoa, and menstrual irregularities have been described with clinical use [see Adverse Reactions (6)].