PREDNISOLONE Drug Interactions: What You Need to Know

INTERACTIONS 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 If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.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.

Anticoagulant

Agents: May enhance or diminish anticoagulant effects. Monitor coagulation indices. (7)

Antidiabetic

Agents: May increase blood glucose concentrations. Dose adjustments of antidiabetic agents may be required. (7) CYP 3A4 inducers and inhibitors: May, respectively, increase or decrease clearance of corticosteroids, necessitating dose adjustment. (7) Cyclosporine: Increase in activity of both, cyclosporine and corticosteroid when administered concurrently. Convulsions have been reported with concurrent use. (7) NSAIDS including aspirin and salicylates: Increased risk of gastrointestinal side effects. (7)

CONTRAINDICATIONS Sulfacetamide Sodium and Prednisolone Sodium Phosphate Ophthalmic Solution is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. This product is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation, to other sulfonamides, or to other corticosteroids. (Hypersensitivity to the antimicrobial components occurs at a higher rate than for other components).

AND PRECAUTIONS Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome and hyperglycemia: Monitor patients for these conditions with chronic use. Taper doses gradually for withdrawal after chronic use. (5.1) Immunosuppression and Increased Risk of Infection: Increased susceptibility to new infection and increased risk of exacerbation, dissemination, or reactivation of latent infection. Signs and symptoms of infection may be masked. (5.2) Elevated blood pressure, salt and water retention and hypokalemia: Monitor blood pressure and sodium, potassium serum levels. (5.3) GI perforation: increased risk in patients with certain GI disorders. Signs and symptoms may be masked. (5.4) Behavioral and mood disturbances: May include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis. Existing conditions may be aggravated. (5.5) Decrease in bone density: Monitor bone density in patients receiving long term corticosteroid therapy. (5.6) Ophthalmic effects: May include cataracts, infections and glaucoma. Monitor intraocular pressure if corticosteroid therapy is continued for more than 6 weeks. (5.7) Live or live attenuated vaccines: Do not administer to patients receiving immunosuppressive doses of corticosteroids. (5.8) Negative effects on growth and development: Monitor pediatric patients on long-term corticosteroid therapy. (5.9) Embryo-Fetal Toxicity: Can cause fetal harm with first trimester use. Advise patients of potential harm to the fetus. (5.10)

5.1 Alterations in Endocrine Function Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and hyperglycemia. Monitor patients for these conditions with chronic use. Corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Drug induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. Mineralocorticoid supplementation is of particular importance in infancy. Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.

5.2 Immunosuppression and Increased Risk of Infection Corticosteroids, including prednisolone sodium phosphate orally disintegrating tablets, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: Reduce resistance to new infections Exacerbate existing infections Increase the risk of disseminated infections Increase the risk of reactivation or exacerbation of latent infections 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 prednisolone sodium phosphate orally disintegrating tablets withdrawal or dosage reduction as needed. Tuberculosis If prednisolone sodium phosphate orally disintegrating tablet is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged prednisolone sodium phosphate orally disintegrating tablets therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis.

Varicella

Zoster and Measles Viral Infections Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteroids, including prednisolone sodium phosphate orally disintegrating tablets. In corticosteroid-treated patients who have not had these diseases or are non-immune, particular care should be taken to avoid exposure to varicella and measles: If a prednisolone sodium phosphate orally disintegrating tablet-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. If varicella develops, treatment with antiviral agents may be considered. If a prednisolone sodium phosphate orally disintegrating tablet-treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated. Hepatitis B Virus Reactivation Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids, including prednisolone sodium phosphate orally disintegrating tablets. Reactivation can also occur infrequently in corticosteroid-treated patients who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with prednisolone sodium phosphate orally disintegrating tablets. For patients who show evidence of hepatitis B infection, recommend consultation with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy.

Fungal Infections

Corticosteroids, including prednisolone sodium phosphate orally disintegrating tablets, may exacerbate systemic fungal infections; therefore, avoid prednisolone sodium phosphate orally disintegrating tablets use in the presence of such infections unless prednisolone sodium phosphate orally disintegrating tablet is needed to control drug reactions. For patients on chronic prednisolone sodium phosphate orally disintegrating tablets therapy who develop systemic fungal infections, prednisolone sodium phosphate orally disintegrating tablets withdrawal or dosage reduction is recommended.

Amebiasis

Corticosteroids, including prednisolone sodium phosphate orally disintegrating tablets, may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating prednisolone sodium phosphate orally disintegrating tablets in patients who have spent time in the tropics or patients with unexplained diarrhea.

Strongyloides Infestation

Corticosteroids, including prednisolone sodium phosphate orally disintegrating tablets, should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, 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.

Cerebral Malaria

Avoid corticosteroids, including prednisolone sodium phosphate orally disintegrating tablets, in patients with cerebral malaria.

5.3 Alterations in Cardiovascular/Renal Function Corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium and calcium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. These agents should be used with caution in patients with hypertension, congestive heart failure, or renal insufficiency. Literature reports suggest an association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with caution in these patients.

5.4 Use in Patients with Gastrointestinal Disorders There is an increased risk of gastrointestinal (GI) perforation in patients with certain GI disorders. Signs of GI perforation, such as peritoneal irritation, may be masked in patients receiving corticosteroids. Corticosteroids should be used with caution if there is a probability of impending perforation, abscess or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; and active or latent peptic ulcer.

5.5 Behavioral and Mood Disturbances Corticosteroid use may be associated with central nervous system effects ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

5.6 Decrease in Bone Density Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., 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 to inhibition of bone growth in children and adolescents and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy and bone density should be monitored in patients on long term corticosteroid therapy.

5.7 Ophthalmic Effects Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored. Patients with Ocular Herpes Simplex Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation. Corticosteroids should not be used in active ocular herpes simplex.

5.8 Vaccination Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered; however, the response to such vaccines cannot be predicted. Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison's disease. While on corticosteroid therapy, patients should not be vaccinated against smallpox. Other immunization 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.

5.9 Effect on Growth and Development Long-term use of corticosteroids can have negative effects on growth and development in children. Growth and development of pediatric patients on prolonged corticosteroid therapy should be carefully monitored.

5.10 Embryo-Fetal Toxicity Prednisolone can cause fetal harm when administered to a pregnant woman. Human studies suggest a small but inconsistent increased risk of orofacial clefts with use of corticosteroids during the first trimester of pregnancy. Published animal studies show prednisolone to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring. Intrauterine growth restriction and decreased birth weight have also been reported with corticosteroid use during pregnancy, however, the underlying maternal condition may also contribute to these risks. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, advise the patient about the potential harm to the fetus. <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1) ]</span> .

5.11 Neuromuscular Effects Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. <span class="opacity-50 text-xs">[see Dosage and Administration (2) ]</span> . An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

5.12 Kaposi&apos;s Sarcoma Kaposi&apos;s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.