氢化泼尼松磷酸钠分散片说明书(英文)

氢化泼尼松磷酸钠分散片说明书(英文) _____________________________________________________________________________________________________________________________ _____________________________________________________________________________________________________________________________________ HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Orapred ODT?? safely and effectively. See full prescribing information for Orapred ODT. Orapred ODT?? prednisolone sodium phosphate orally disintegrating tablets Initial U.S. Approval: 1955 ----------------------------INDICATIONS AND USAGE--------------------------- 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 ----------------------DOSAGE AND ADMINISTRATION----------------------- Individualize dosing based on disease severity and patient response 2: ?? Initial Dose: 10 mg to 60 mg of prednisolone as 13.4 mg to 80.6 mg of prednisolone sodium phosphate ?? Maintenance Dose: Use lowest dosage that will maintain an adequate clinical response ?? Discontinuation: Withdraw gradually if discontinuing long-term or high-dose therapy ?? Take with food to avoid gastrointestinal GI irritation DO NOT BREAK OR USE PARTIAL ORAPRED ODT TABLETS. USE AN APPROPRIATE FORMULATION OF PREDNISOLONE IF INDICATED DOSE CANNOT BE OBTAINED USING ORAPRED ODT. --------------------DOSAGE FORMS AND STRENGTHS---------------------- Orally Disintegrating Tablets: ?? 10 mg Tablets as 13.4 mg prednisolone sodium phosphate 3 ?? 15 mg Tablets as 20.2 mg prednisolone sodium phosphate 3 ?? 30 mg Tablets as 40.3 mg prednisolone sodium phosphate 3 ?? -------------------------------CONTRAINDICATIONS------------------------------ ?? Hypersensitivity to prednisolone or any components of this product. 4 -----------------------WARNINGS AND PRECAUTIONS------------------------ ?? Hypothalamic-pituitary-adrenal HPA axis suppression Cushings syndrome and hyperglycemia: Monitor patients for these conditions with chronic use Taper doses gradually for withdrawal after chronic use. 5.1 ?? Infections: 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 ?? Decreases 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 ?? Use in pregnancy: Fetal harm can occur with first trimester use. Apprise women of potential harm to the fetus. 5.10 ------------------------------ADVERSE REACTIONS------------------------------- 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 Sciele Drug Safety Department at 1-800-849-9707 ext. 1454 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ------------------------------DRUG INTERACTIONS------------------------------- ?? 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 administer concurrently. Convulsions have been reported with concurrent use. 7 ?? NSAIDS including aspirin and salicylates: Increased risk of gastrointestinal side effects. 7 See 17 for PATIENT COUNSELING INFORMATION Revised 07/2010 FULL PRESCRIBING INFORMATION: CONTENTS?? 1 INDICATIONS AND USAGE 1.1 Allergic States 1.2 Dermatologic Diseases 1.3 Endocrine Conditions 1.4 Gastrointestinal Diseases 1.5 Hematologic Diseases 1.6 Neoplastic Conditions 1.7 Nervous System Conditions 1.8 Ophthalmic Conditions 1.9 Conditions related to Organ Transplantation 1.10 Pulmonary Diseases 1.11 Renal Conditions 1.12 Rheumatic Conditions 1.13 Specific Infectious Diseases 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing 2.2 Recommended Monitoring 2.3 Corticosteroid Comparison Chart 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Alteration of Endocrine Function 5.2 Increased Risks Related to Infections 5.3 Alterations in Cardiovascular/Renal Function 5.4 Use in Patients with Gastrointestinal Disorders 5.5 Behavioral and Mood Disturbances 5.6 Decrease in Bone Density 5.7 Ophthalmic Effects 5.8 Vaccination 5.9 Effect on Growth and Development 5.10 Use in Pregnancy 5.11 Neuromuscular Effects 5.12 Kaposis Sarcoma 6 ADVERSE REACTIONS 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis Mutagenesis Impairment of Fertility 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION ??Sections or subsections omitted from the full prescribing information are not listed 1 FULL PRESCRIBING INFORMATION INDICATIONS AND USAGE Orapred ODT prednisolone sodium phosphate orally disintegrating tablet is indicated in the treatment of the following diseases or conditions: 1.1 Allergic Conditions 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 1.2 Dermatologic Diseases ?? Bullous dermatitis herpetiformis ?? Contact dermatitis ?? Exfoliative erythroderma ?? Mycosis fungoides ?? Pemphigus ?? Severe erythema multiforme Stevens-Johnson syndrome 1.3 Endocrine Conditions ?? 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. 1.4 Gastrointestinal Diseases During acute episodes in: ?? Crohn’s Disease ?? Ulcerative colitis 1.5 Hematologic Diseases ?? Acquired autoimmune hemolytic anemia ?? Diamond-Blackfan anemia ?? Idiopathic thrombocytopenic purpura in adults ?? Pure red cell aplasia ?? Secondary thrombocytopenia in adults 1.6 Neoplastic Conditions For the treatment of: ?? Acute leukemia ?? Aggressive lymphomas 1.7 Nervous System Conditions ?? Acute exacerbations of multiple sclerosis ?? Cerebral edema associated with primary or metastatic brain tumor craniotomy or head injury 1.8 Ophthalmic Conditions ?? Sympathetic ophthalmia ?? Uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids 1.9 Conditions Related to Organ Transplantation ?? Acute or chronic solid organ rejection 1.10 Pulmonary Diseases ?? 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 NDA 21-959/S-004 Page 3 1.11 Renal Conditions To induce a diuresis or remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus 1.12 Rheumatologic Conditions 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 1.13 Specific Infectious Diseases ?? Trichinosis with neurologic or myocardial involvement ?? Tuberculous meningitis with subarachnoid block or impending block used concurrently with appropriate antituberculous chemotherapy 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing 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. Use an appropriate formulation of prednisolone if indicated dose cannot be obtained using Orapred ODT. This may become important in the treatment of conditions that require tapering doses that cannot be adequately accommodated by Orapred ODT e.g. tapering the dose below 10 mg. 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 In the treatment of acute exacerbations of multiple sclerosis daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for one month have been shown to be effective. Pediatric In pediatric patients the initial dose of Orapred may vary depending on the specific disease entity being treated. The range of initial doses is 0.14 to 2 mg/kg/day in three or four divided doses 4 to 60 mg/m2bsa/day. NDA 21-959/S-004 Page 4 Nephrotic Syndrome The standard regimen used to treat nephrotic syndrome in pediatric patients is 60 mg/m2/day given in three divided doses for 4 weeks followed by 4 weeks of single dose alternate-day therapy at 40 mg/m2/day. Asthma The National Heart Lung and Blood Institute NHLBI recommended dosing for systemic prednisone prednisolone or methylprednisolone in children whose asthma is uncontrolled by inhaled corticosteroids and long-acting bronchodilators is 1-2 mg/kg/day in single or divided doses. 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. 2.2 Recommended Monitoring 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. 2.3 Corticosteroid Comparison Chart 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. 3 DOSAGE FORMS AND STRENGTHS Orally disintegrating tablets: ?? 10 mg prednisolone as 13.4 mg prednisolone sodium phosphate ?? 15 mg prednisolone as 20.2 mg prednisolone sodium phosphate ?? 30 mg prednisolone as 40.3 mg prednisolone sodium phosphate 4 CONTRAINDICATIONS 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. 5 WARNINGS AND PRECAUTIONS 5.1 Alterations in Endocrine Function Hypothalamic-pituitary-adrenal HPA axis suppression Cushings 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 an.