ORAPRED_ODT- prednisolone sodium phosphate_tablet, orally disintegrating

Prednisolone is a synthetic adrenocortical steroid drug with predominantly glucocorticoid properties. Some of these properties reproduce the physiological actions of endogenous glucocorticosteroids, but others do not necessarily reflect any of the adrenal hormones' normal functions; they are seen only after administration of large therapeutic doses of the drug. The pharmacological effects of prednisolone which are due to its glucocorticoid properties include: promotion of gluconeogenesis; increased deposition of glycogen in the liver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism of protein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged); and increased calcium excretion. Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited. Prednisolone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisolone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension. Absorption: Table 1. Comparison of Mean Pharmacokinetic Parameters (%CV) in Healthy Volunteers Following a Single Dose of 30 mg Orapred ODT and Pediapred Solution, Dose Administered under fasting conditions. AUC 0- infinity C max Mean values of 21 normal volunteers (30 mg prednisolone base equivalent) (+/- S. ) Pediapred Solution 2426. 94) Orapred ODT 2408. 28) Distribution: Metabolism: Excretion: Special Populations ss.

Orapred ODT (prednisolone sodium phosphate orally disintegrating tablet) is indicated in the treatment of the following diseases or conditions: Orapred ODT is a corticosteroid indicated as an anti-inflammatory or immunosuppressive agent for certain allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, specific infectious diseases or conditions and organ transplantation ( 1 for the treatment of certain endocrine conditions ( 1 for palliation of certain neoplastic conditions ( 1 Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in adult and pediatric populations with: Atopic dermatitis Drug hypersensitivity reactions Seasonal or perennial allergic rhinitis Serum sickness Bullous dermatitis herpetiformis Contact dermatitis Exfoliative erythroderma Mycosis fungoides Pemphigus Severe erythema multiforme (Stevens-Johnson syndrome) Congenital adrenal hyperplasia Hypercalcemia of malignancy Nonsuppurative thyroiditis Primary or secondary adrenocortical insufficiency: hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable. During acute episodes in: Crohn's Disease Ulcerative colitis Acquired (autoimmune) hemolytic anemia Diamond-Blackfan anemia Idiopathic thrombocytopenic purpura in adults Pure red cell aplasia Secondary thrombocytopenia in adults For the treatment of: Acute leukemia Aggressive lymphomas Acute exacerbations of multiple sclerosis Cerebral edema associated with primary or metastatic brain tumor, craniotomy or head injury Sympathetic ophthalmia Uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids Acute or chronic solid organ rejection Acute exacerbations of chronic obstructive pulmonary disease (COPD) Allergic bronchopulmonary aspergillosis Aspiration pneumonitis Asthma Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate chemotherapy Hypersensitivity pneumonitis Idiopathic bronchiolitis obliterans with organizing pneumonia Idiopathic eosinophilic pneumonias Idiopathic pulmonary fibrosis Pneumocystis carinii pneumonia (PCP) associated with hypoxemia occurring in an HIV (+) individual who is also under treatment with appropriate anti-PCP antibiotics Symptomatic sarcoidosis To induce a diuresis or remission of proteinuria in nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus As adjunctive therapy for short term administration (to tide the patient over an acute episode or exacerbation) in: Acute gouty arthritis During an exacerbation or as maintenance therapy in selected cases of: Ankylosing spondylitis Dermatomyositis /polymyositis Polymyalgia rheumatica/temporal arteritis Psoriatic arthritis Relapsing polychondritis Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low dose maintenance therapy) Sjogren's syndrome Systemic lupus erythematosus Vasculitis Trichinosis with neurologic or myocardial involvement Tuberculous meningitis with subarachnoid block or impending block, used concurrently with appropriate antituberculous chemotherapy.

Individualize dosing based on disease severity and patient response: Initial Dose: 10 mg to 60 mg of prednisolone (as 13. 6 mg of prednisolone sodium phosphate) ( 2 Maintenance Dose: Use lowest dosage that will maintain an adequate clinical response ( 2 Discontinuation: Withdraw gradually if discontinuing long-term or high-dose therapy ( 2 Take with food to avoid gastrointestinal (GI) irritation ( 2 DO NOT BREAK OR USE PARTIAL ORAPRED ODT TABLETS. USE AN APPROPRIATE FORMULATION OF PREDNISOLONE IF INDICATED DOSE CANNOT BE OBTAINED USING ORAPRED ODT. ( 2 Dosage of Orapred ODT should be individualized according to the severity of the disease and the response of the patient. For pediatric patients, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight. Do not break or use partial Orapred ODT tablets. The initial dose of Orapred ODT may vary from 10 to 60 mg (prednisolone base) per day, depending on the specific disease entity being treated. In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time, there is a lack of satisfactory clinical response, Orapred should be discontinued and the patient placed on other appropriate therapy. IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage that will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation it may be necessary to increase the dosage of Orapred ODT for a period of time consistent with the patient's condition. If after long term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly. Orapred ODT are packaged in a blister. Patients should be instructed not to remove the tablet from the blister until just prior to dosing. The blister pack should then be peeled open, and the orally disintegrating tablet placed on the tongue, where tablets may be swallowed whole as any conventional tablet, or allowed to dissolve in the mouth, with or without the assistance of water. Orally disintegrating tablet dosage forms are friable and are not intended to be cut, split, or broken. Multiple Sclerosis Pediatric 2 Nephrotic Syndrome 2 2 Asthma prednisone, prednisolone or methylprednisolone It is further recommended that short course, or "burst" therapy, be continued until a child achieves a peak expiratory flow rate of 80% of his or her personal best or symptoms resolve. This usually requires 3 to 10 days of treatment, although it can take longer. There is no evidence that tapering the dose after improvement will prevent a relapse. Blood pressure, body weight, routine laboratory studies, including serum potassium and fasting blood glucose, should be obtained at regular intervals during prolonged therapy. Appropriate diagnostic studies should be performed in patients with known or suspected peptic ulcer disease and in patients at risk for reactivation of latent tuberculosis infections. For the purpose of comparison, one 10 mg Orapred ODT tablet (13. 4 mg prednisolone sodium phosphate) is equivalent to the following milligram dosage of the various glucocorticoids: Betamethasone 1. 75 mg Paramethasone 4 mg Cortisone 50 mg Prednisolone 10 mg Dexamethasone 1. 75 mg Prednisone 10 mg Hydrocortisone 40 mg Triamcinolone 8 mg Methylprednisolone 8 mg These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain. Allergic Reactions: Cardiovascular: Dermatologic: Endocrine: Fluid and Electrolyte Disturbances: Gastrointestinal: General: Metabolic: Musculoskeletal: Neurological: Ophthalmic: Reproductive: Postmarketing Experience Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain. ( 6 To report SUSPECTED ADVERSE REACTIONS, contact Advanz Pharma (US) Corp. at 1-877-370-1142 or FDA at 1-800-FDA-1088 or www. gov/medwatch.

Orapred ODT is contraindicated in patients who are hypersensitive to corticosteroids such as prednisolone or any components of this product. Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy. Hypersensitivity to prednisolone or any components of this product.

Risk Summary (see Data) [see Warnings and Precautions (5. 10) (see Clinical Considerations) (see Data) Clinical Considerations Fetal/Neonatal Adverse Reactions [see Warnings and Precautions ( 5. 1 )] Data Human Data Animal Data 2 2 Risk Summary (see Clinical Considerations) [see Use in Specific Populations ( 8. Clinical Considerations The efficacy and safety of prednisolone in the pediatric population are based on the well-established course of effect of corticosteroids, which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (>2 years of age), and aggressive lymphomas and leukemias (>1 month of age). However, some of these conclusions and other indications for pediatric use of corticosteroid, e. , severe asthma and wheezing, are based on adequate and well-controlled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations. The adverse effects of prednisolone in pediatric patients are similar to those in adults [see Adverse Reactions (6) ] Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA axis function. The linear growth of children treated with corticosteroids by any route should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of other treatment alternatives. In order to minimize the potential growth effects of corticosteroids, children should be titrated to the lowest effective dose. No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and other reported clinical experience with prednisolone has not identified differences in responses between the elderly and younger patients. However, the incidence of corticosteroid-induced side effects may be increased in geriatric patients and appear to be dose-related. Osteoporosis is the most frequently encountered complication, which occurs at a higher incidence rate in corticosteroid-treated geriatric patients as compared to younger populations and in age-matched controls. Losses of bone mineral density appear to be greatest early on in the course of treatment and may recover over time after steroid withdrawal or use of lower doses (i. , <=5 mg/day). Prednisolone doses of 7. 5 mg/day or higher, have been associated with an increased relative risk of both vertebral and nonvertebral fractures, even in the presence of higher bone density compared to patients with involutional osteoporosis. Routine screening of geriatric patients, including regular assessments of bone mineral density and institution of fracture prevention strategies, along with regular review of Orapred indication should be undertaken to minimize complications and keep the Orapred dose at the lowest acceptable level. Co-administration of bisphosphonates has been shown to retard the rate of bone loss in corticosteroid-treated males and postmenopausal females, and these agents are recommended in the prevention and treatment of corticosteroid-induced osteoporosis. It has been reported that equivalent weight-based doses yield higher total and unbound prednisolone plasma concentrations and reduced renal and non-renal clearance in elderly patients compared to younger populations. However, it is not clear whether dosing reductions would be necessary in elderly patients, since these pharmacokinetic alterations may be offset by age-related differences in responsiveness of target organs and/or less pronounced suppression of adrenal release of cortisol. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Aminoglutethimide: Amphotericin B: Anticholinesterase agents: Anticoagulant agents: Antidiabetic Agents: Antitubercular drugs: CYP 3A4 inducers (e. barbiturates, phenytoin, carbamazepine, and rifampin): CYP 3A4 inhibitors (e. , ketoconazole, macrolide antibiotics): Cholestyramine: Cyclosporine: Digitalis: Estrogens, including oral contraceptives: NSAIDS, including aspirin and salicylates: Potassium-depleting agents (e. , diuretics, Amphotericin B): Skin Tests: Toxoids and live or inactivated 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.

OVERDOSAGE
The effects of accidental ingestion of large quantities of prednisolone over a very short period of time have not been reported, but prolonged use of the drug can produce mental symptoms, moon face, abnormal fat deposits, fluid retention, excessive appetite, weight gain, hypertrichosis, acne, striae, ecchymosis, increased sweating, pigmentation, dry scaly skin, thinning scalp hair, increased blood pressure, tachycardia, thrombophlebitis, decreased resistance to infection, negative nitrogen balance with delayed bone and wound healing, headache, weakness, menstrual disorders, accentuated menopausal symptoms, neuropathy, fractures, osteoporosis, peptic ulcer, decreased glucose tolerance, hypokalemia, and adrenal insufficiency. Hepatomegaly and abdominal distention have been observed in children. Treatment of acute overdosage is by immediate gastric lavage or emesis followed by supportive and symptomatic therapy. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage of prednisolone may be reduced only temporarily, or alternate day treatment may be introduced.
NONCLINICAL TOXICOLOGY
Orapred 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/m 2 2 Orapred 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 Escherichia coli Orapred 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) ].

Advanz Pharma (US) Corp.

ORAPRED_ODT- prednisolone sodium phosphate_tablet, orally disintegrating Product manual source documgent