CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Naturally occurring glucocorticoids (hydrocortisone), which also have salt-retainingproperties, are used as replacement therapy in adrenocortical deficiency states. Theirsynthetic analogs are primarily used for their potent anti-inflammatory effects in disordersof many organ systems.Prednisolone is synthetic adrenocortical steroid drug with predominantly glucocorticoidproperties. Some of these properties reproduce the physiological actions of endogenousglucocorticosteroids, but others do not necessarily reflect any of the adrenal hormonesnormal functions; they are seen only after administration of large therapeutic doses of thedrug. The pharmacological effects of prednisolone which are due to its glucocorticoidproperties include: promotion of gluconeogenesis; increased deposition of glycogen in theliver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism ofprotein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerularfiltration rate and resulting increase in urinary excretion of urate (creatinine excretion remainsunchanged); and increased calcium excretion.Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis andproduction 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. Suppressionof the production of corticotropin may lead to suppression of endogenous corticosteroids.Prednisolone has slight mineralocorticoid activity, whereby entry of sodium into cells andloss of intracellular potassium is stimulated. This is particularly evident in the kidney, whererapid ion exchange leads to sodium retention and hypertension.Prednisolone is rapidly and well absorbed from the gastrointestinal tract following oraladministration. Prednisolone Sodium Phosphate Oral Solution produces 14% higher peakplasma level of prednisolone which occurs 20% faster than that seen with tablets.Prednisolone is 70-90% protein-bound in the plasma and it is eliminated from the plasmawith half-life of to hours. It is metabolized mainly in the liver and excreted in the urineas sulfate and glucuronide conjugates.The systemic availability, metabolism and elimination of prednisolone after administration ofsingle weight-based doses (0.8 mg/kg) of intravenous (IV) prednisolone and oral prednisonewere reported in small study of 19 young (23 to 34 years) and 12 elderly (65 to 89 years)subjects. Results showed that the systemic availability of total and unbound prednisolone, aswell as interconversion between prednisolone and prednisone were independent of age. Themean unbound fraction of prednisolone was higher, and the steady-state volume of distribution(Vss) of unbound prednisolone was reduced in elderly patients. Plasma prednisoloneconcentrations were higher in elderly subjects, and the higher AUCs of total and unboundprednisolone were most likely reflective of an impaired metabolic clearance, evidenced byreduced fractional urinary clearance of 6b-hydroxyprednisolone. Despite these findings of highertotal and unbound prednisolone concentrations, elderly subjects had higher AUCs of cortisol,suggesting that the elderly population is less sensitive to suppression of endogenous cortisolor their capacity for hepatic inactivation of cortisol is diminished.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. The initial dosage of Prednisolone Sodium Phosphate Oral Solution may vary from mL to60 mL (5 to 60 mg prednisolone base) per day depending on the specific disease entitybeing treated. In situations of less severity, lower doses will generally suffice while in selectedpatients higher initial doses may be required. The initial dosage should be maintained oradjusted until satisfactory response is noted. If after reasonable period of time, there isa lack of satisfactory clinical response, Prednisolone Sodium Phosphate Oral Solution shouldbe discontinued and the patient placed on other appropriate therapy. IT SHOULD BEEMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BEINDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THERESPONSE OF THE PATIENT. After favorable response is noted, the proper maintenancedosage should be determined by decreasing the initial drug dosage in small decrements atappropriate time intervals until the lowest dosage which will maintain an adequate clinicalresponse is reached. It should be kept in mind that constant monitoring is needed in regardto drug dosage. Included in the situations which may make dosage adjustments necessaryare changes in clinical status secondary to remissions or exacerbations in the diseaseprocess, the patients individual drug responsiveness, and the effect of patient exposure tostressful situations not directly related to the disease entity under treatment; in this lattersituation it may be necessary to increase the dosage of Prednisolone Sodium PhosphateOral Solution for period of time consistent with the patients condition. If after long termtherapy the drug is to be stopped, it is recommended that it be withdrawn gradually ratherthan abruptly.In the treatment of acute exacerbations of multiple sclerosis, daily doses of 200 mg ofprednisolone for week followed by 80 mg every other day or to mg dexamethasoneevery other day for one month have been shown to be effective.In pediatric patients, the initial dose of Prednisolone Sodium Phosphate Oral Solutionmay vary depending on the specific disease entity being treated. The range of initial dosesis 0.14 to mg/kg/day in three or four divided doses (4 to 60 mg/m2bsa/day).The standard regimen used to treat nephrotic syndrome in pediatric patients is 60 mg/m2/daygiven in three divided doses for weeks, followed by weeks of single dose alternate-daytherapy at 40 mg/m2/day.The National Heart, Lung, and Blood Institute (NHLBI) recommended dosing for systemicprednisone, prednisolone or methylprednisolone in children whose asthma is uncontrolledby inhaled corticosteroids and long-acting bronchodilators is 1-2 mg/kg/day in single ordivided doses. It is further recommended that short course, or burst therapy, be continueduntil child achieves peak expiratory flow rate of 80% of his or her personal best orsymptoms resolve. This usually requires to 10 days of treatment, although it can takelonger. There is no evidence that tapering the dose after improvement will prevent relapse.For the purpose of comparison, the following is the equivalent milligram dosage of thevarious glucocorticoids: Cortisone, 25 Triamcinolone, Hydrocortisone, 20Paramethasone, Prednisolone, Betamethasone, 0.75 Prednisolone, 5Dexamethasone, 0.75 Methylprednisolone, 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.

DRUG INTERACTIONS SECTION.

Drug Interactions. Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepaticmicrosomal drug metabolizing enzyme activity may enhance metabolism of prednisoloneand require that the dosage of Prednisolone Sodium Phosphate Oral Solution be increased.Increased activity of both cyclosporin and corticosteroids may occur when the two are usedconcurrently. Convulsions have been reported with this concurrent use.Estrogens may decrease the hepatic metabolism of certain corticosteroids thereby increasingtheir effect.Ketoconazole has been reported to decrease the metabolism of certain corticosteroids byup to 60% leading to an increased risk of corticosteroid side effects.Coadministration of corticosteroids and warfarin usually results in inhibition of response towarfarin, although there have been some conflicting reports. Therefore, coagulation indicesshould be monitored frequently to maintain the desired anticoagulant effect.Concomitant use of aspirin (or other non-steroidal anti-inflammatory agents) andcorticosteroids increases the risk of gastrointestinal side effects. Aspirin should be usedcautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance ofsalicylates may be increased with concurrent use of corticosteroids.When corticosteroids are administered concomitantly with potassium-depleting agents(i.e., diuretics, amphotericin-B), patients should be observed closely for development ofhypokalemia. Patients on digitalis glycosides may be at increased risk of arrhythmias dueto hypokalemia.Concomitant use of anticholinesterase agents and corticosteroids may produce severeweakness in patients with myasthenia gravis. If possible, anticholinesterase agents shouldbe withdrawn at least 24 hours before initiating corticosteroid therapy.Due to inhibition of antibody response, patients on prolonged corticosteroid therapy mayexhibit diminished response to toxoids and live or inactivated vaccines. Corticosteroidsmay also potentiate the replication of some organisms contained in live attenuated vaccines.If possible, routine administration of vaccines or toxoids should be deferred untilcorticosteroid therapy is discontinued.Because corticosteroids may increase blood glucose concentrations, dosage adjustmentsof antidiabetic agents may be required.Corticosteroids may suppress reactions to skin tests.

GENERAL PRECAUTIONS SECTION.

General. The lowest possible dose of corticosteroid should be used to control the condition undertreatment, and when reduction in dosage is possible, the reduction should be gradual.Since complications of treatment with glucocorticoids are dependent on the size of thedose and the duration of treatment, risk/benefit decision must be made in each individualcase as to dose and duration of treatment and as to whether daily or intermittent therapyshould be used.There is an enhanced effect of corticosteroids in patients with hypothyroidism and in thosewith cirrhosis.Cardio-renalAs sodium retention with resultant edema and potassium loss may occur in patientsreceiving corticosteroids, these agents should be used with caution in patients withhypertension, congestive heart failure, or renal insufficiency.EndocrineDrug-induced secondary adrenocortical insufficiency may be minimized by gradual reductionof dosage. This type of relative insufficiency may persist for months after discontinuationof therapy; therefore, in any situation of stress occurring during that period, hormone therapyshould be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or amineralocorticoid should be administered concurrently.GastrointestinalSteroids should be used with caution in nonspecific ulcerative colitis, if there is probabilityof impending perforation, abscess or other pyogenic infection; diverticulitis; fresh intestinalanastomoses; active or latent peptic ulcer.Signs of peritoneal irritation following gastrointestinal perforation in patients receivingcorticosteroids may be minimal or absent.MusculoskeletalCorticosteroids decrease bone formation and increase bone resorption both through theireffect on calcium regulation (i.e., decreasing absorption and increasing excretion) andinhibition of osteoblast function. This, together with decrease in the protein matrix of thebone 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 ofosteoporosis at any age. Special consideration should be given to patients at increased riskof osteoporosis (i.e., postmenopausal women) before initiating corticosteroid therapy.Neuro-psychiatricAlthough controlled clinical trials have shown corticosteroids to be effective in speedingthe resolution of acute exacerbations of multiple sclerosis, they do not show that theyaffect the ultimate outcome or natural history of the disease. The studies do show thatrelatively high doses of corticosteroids are necessary to demonstrate significant effect.(See DOSAGE AND ADMINISTRATION)An acute myopathy has been observed with the use of high doses of corticosteroids, mostoften occurring in patients with disorders of neuromuscular transmission (e.g., myastheniagravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs(e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratorymuscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinicalimprovement or recovery after stopping corticosteroids may require weeks to years.Psychic derangements may appear when corticosteroids are used, ranging from euphoria,insomnia, mood swings, personality changes, and severe depression, to frank psychoticmanifestations. Also, existing emotional instability or psychotic tendencies may beaggravated by corticosteroids.OphthalmicIntraocular pressure may become elevated in some individuals. If steroid therapy iscontinued for more than weeks, intraocular pressure should be monitored.Information for PatientsPatients should be warned not to discontinue the use of Prednisolone Sodium PhosphateOral Solution abruptly or without medical supervision, to advise any medical attendants thatthey are taking Prednisolone Sodium Phosphate Oral Solution and to seek medical adviceat once should they develop fever or other signs of infection.Persons who are on immunosuppressant doses of corticosteroids should be warned toavoid exposure to chicken pox or measles. Patients should also be advised that if they areexposed, medical advice should be sought without delay.

GERIATRIC USE SECTION.

Geriatric Use. Clinical studies of Prednisolone Sodium Phosphate Oral Solution did not include sufficientnumbers of subjects aged 65 and over to determine whether they respond differently fromyounger subjects. Other reported clinical experience with prednisolone sodium phosphatehas not identified differences in responses between the elderly and younger patients.However, the incidence of corticosteroid-induced side effects may be increased in geriatricpatients and appear to be dose-related. Osteoporosis is the most frequently encounteredcomplication, which occurs at higher incidence rate in corticosteroid-treated geriatricpatients as compared to younger populations and in age-matched controls. Losses of bonemineral density appear to be greatest early on in the course of treatment and may recoverover time after steroid withdrawal or use of lower doses (i.e., <= mg/day). Prednisolonedoses of 7.5 mg/day or higher have been associated with an increased relative risk of bothvertebral and nonvertebral fractures, even in the presence of higher bone density comparedto patients with involutional osteoporosis.Routine screening of geriatric patients, including regular assessments of bone mineraldensity and institution of fracture prevention strategies, along with regular review ofprednisolone indication should be undertaken to minimize complications and keep theprednisolone dose at the lowest acceptable level. Co-administration of bisphosphonates hasbeen shown to retard the rate of bone loss in corticosteroid-treated males andpostmenopausal females, and these agents are recommended in the prevention andtreatment of corticosteroid-induced osteoporosis.It has been reported that equivalent weight-based doses yield higher total and unboundprednisolone plasma concentrations and reduced renal and non-renal clearance in elderlypatients compared to younger populations. However, it is not clear whether dosing reductionswould be necessary in elderly patients, since these pharmacokinetic alterations may be offsetby age-related differences in responsiveness of target organs and/or less pronouncedsuppression of adrenal release of cortisol. Dose selection for an elderly patient should becautious, usually starting at the low end of the dosing range, reflecting the greater frequency ofdecreased 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 reactionsto this drug may be greater in patients with impaired renal function. Because elderly patientsare more likely to have decreased renal function, care should be taken in dose selection,and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY).

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Prednisolone Sodium Phosphate Oral Solution is indicated in the following conditions:1. Allergic StatesControl of severe or incapacitating allergic conditions intractable to adequate trials ofconventional treatment in adult and pediatric populations with: seasonal or perennialallergic rhinitis; asthma; contact dermatitis; atopic dermatitis; serum sickness; drughypersensitivity reactions. 2. Dermatologic Diseases Pemphigus; bullous dermatitis herpetiformis; severe erythema multiforme (Stevens-Johnsonsyndrome); exfoliative erythroderma; mycosis fungoides. 3. Edematous States To induce diuresis or remission of proteinuria in nephrotic syndrome in adults with lupuserythematosus and in adults and pediatric populations, with idiopathic nephrotic syndrome,without uremia. 4. Endocrine Disorders Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the firstchoice; synthetic analogs may be used in conjunction with mineralocorticoids whereapplicable; in infancy mineralocorticoid supplementation is of particular importance); congenitaladrenal hyperplasia; hypercalcemia associated with cancer; nonsuppurative thyroiditis. 5. Gastrointestinal Diseases To tide the patient over critical period of the disease in: ulcerative colitis; regional enteritis. 6. Hematologic Disorders Idiopathic thrombocytopenic purpura in adults; selected cases of secondary thrombocytopenia;acquired (autoimmune) hemolytic anemia; pure red cell aplasia; Diamond-Blackfan anemia. 7. Neoplastic Diseases For the treatment of acute leukemia and aggressive lymphomas in adults and children. 8. Nervous System Acute exacerbations of multiple sclerosis. 9. Ophthalmic Diseases Uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids; temporalarteritis; sympathetic ophthalmia. 10. Respiratory Diseases Symptomatic sarcoidosis; idiopathic eosinophilic pneumonias; fulminating or disseminatedpulmonary tuberculosis when used concurrently with appropriate antituberculouschemotherapy; asthma (as distinct from allergic asthma listed above under Allergic States),hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, acute exacerbations of chronicobstructive pulmonary disease (COPD), and Pneumocystis carinii pneumonia (PCP)associated with hypoxemia occurring in an HIV (+) individual who is also under treatmentwith appropriate anti- PCP antibiotics. Studies support the efficacy of systemic corticosteroidsfor the treatment of these conditions: allergic bronchopulmonary aspergillosis, idiopathicbronchiolitis obliterans with organizing pneumonia. 11. Rheumatic Disorders As adjunctive therapy for short term administration (to tide the patient over an acute episodeor exacerbation) in: psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoidarthritis (selected cases may require low dose maintenance therapy); ankylosing spondylitis;acute and subacute bursitis; acute nonspecific tenosynovitis; acute gouty arthritis;epicondylitis. For the treatment of systemic lupus erythematosus, dermatomyositis(polymyositis), polymyalgia rheumatica, Sjogrens syndrome, relapsing polychondritis, andcertain cases of vasculitis. 12. Miscellaneous Tuberculous meningitis with subarachnoid block or impending block, tuberculosis withenlarged mediastinal lymph nodes causing respiratory difficulty, and tuberculosis with pleuralor pericardial effusion (appropriate antituberculous chemotherapy must be used concurrentlywhen treating any tuberculosis complications); Trichinosis with neurologic or myocardialinvolvement; acute or chronic solid organ rejection (with or without other agents).

PRECAUTIONS SECTION.

PRECAUTIONS. General. The lowest possible dose of corticosteroid should be used to control the condition undertreatment, and when reduction in dosage is possible, the reduction should be gradual.Since complications of treatment with glucocorticoids are dependent on the size of thedose and the duration of treatment, risk/benefit decision must be made in each individualcase as to dose and duration of treatment and as to whether daily or intermittent therapyshould be used.There is an enhanced effect of corticosteroids in patients with hypothyroidism and in thosewith cirrhosis.Cardio-renalAs sodium retention with resultant edema and potassium loss may occur in patientsreceiving corticosteroids, these agents should be used with caution in patients withhypertension, congestive heart failure, or renal insufficiency.EndocrineDrug-induced secondary adrenocortical insufficiency may be minimized by gradual reductionof dosage. This type of relative insufficiency may persist for months after discontinuationof therapy; therefore, in any situation of stress occurring during that period, hormone therapyshould be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or amineralocorticoid should be administered concurrently.GastrointestinalSteroids should be used with caution in nonspecific ulcerative colitis, if there is probabilityof impending perforation, abscess or other pyogenic infection; diverticulitis; fresh intestinalanastomoses; active or latent peptic ulcer.Signs of peritoneal irritation following gastrointestinal perforation in patients receivingcorticosteroids may be minimal or absent.MusculoskeletalCorticosteroids decrease bone formation and increase bone resorption both through theireffect on calcium regulation (i.e., decreasing absorption and increasing excretion) andinhibition of osteoblast function. This, together with decrease in the protein matrix of thebone 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 ofosteoporosis at any age. Special consideration should be given to patients at increased riskof osteoporosis (i.e., postmenopausal women) before initiating corticosteroid therapy.Neuro-psychiatricAlthough controlled clinical trials have shown corticosteroids to be effective in speedingthe resolution of acute exacerbations of multiple sclerosis, they do not show that theyaffect the ultimate outcome or natural history of the disease. The studies do show thatrelatively high doses of corticosteroids are necessary to demonstrate significant effect.(See DOSAGE AND ADMINISTRATION)An acute myopathy has been observed with the use of high doses of corticosteroids, mostoften occurring in patients with disorders of neuromuscular transmission (e.g., myastheniagravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs(e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratorymuscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinicalimprovement or recovery after stopping corticosteroids may require weeks to years.Psychic derangements may appear when corticosteroids are used, ranging from euphoria,insomnia, mood swings, personality changes, and severe depression, to frank psychoticmanifestations. Also, existing emotional instability or psychotic tendencies may beaggravated by corticosteroids.OphthalmicIntraocular pressure may become elevated in some individuals. If steroid therapy iscontinued for more than weeks, intraocular pressure should be monitored.Information for PatientsPatients should be warned not to discontinue the use of Prednisolone Sodium PhosphateOral Solution abruptly or without medical supervision, to advise any medical attendants thatthey are taking Prednisolone Sodium Phosphate Oral Solution and to seek medical adviceat once should they develop fever or other signs of infection.Persons who are on immunosuppressant doses of corticosteroids should be warned toavoid exposure to chicken pox or measles. Patients should also be advised that if they areexposed, medical advice should be sought without delay.. Drug Interactions. Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepaticmicrosomal drug metabolizing enzyme activity may enhance metabolism of prednisoloneand require that the dosage of Prednisolone Sodium Phosphate Oral Solution be increased.Increased activity of both cyclosporin and corticosteroids may occur when the two are usedconcurrently. Convulsions have been reported with this concurrent use.Estrogens may decrease the hepatic metabolism of certain corticosteroids thereby increasingtheir effect.Ketoconazole has been reported to decrease the metabolism of certain corticosteroids byup to 60% leading to an increased risk of corticosteroid side effects.Coadministration of corticosteroids and warfarin usually results in inhibition of response towarfarin, although there have been some conflicting reports. Therefore, coagulation indicesshould be monitored frequently to maintain the desired anticoagulant effect.Concomitant use of aspirin (or other non-steroidal anti-inflammatory agents) andcorticosteroids increases the risk of gastrointestinal side effects. Aspirin should be usedcautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance ofsalicylates may be increased with concurrent use of corticosteroids.When corticosteroids are administered concomitantly with potassium-depleting agents(i.e., diuretics, amphotericin-B), patients should be observed closely for development ofhypokalemia. Patients on digitalis glycosides may be at increased risk of arrhythmias dueto hypokalemia.Concomitant use of anticholinesterase agents and corticosteroids may produce severeweakness in patients with myasthenia gravis. If possible, anticholinesterase agents shouldbe withdrawn at least 24 hours before initiating corticosteroid therapy.Due to inhibition of antibody response, patients on prolonged corticosteroid therapy mayexhibit diminished response to toxoids and live or inactivated vaccines. Corticosteroidsmay also potentiate the replication of some organisms contained in live attenuated vaccines.If possible, routine administration of vaccines or toxoids should be deferred untilcorticosteroid therapy is discontinued.Because corticosteroids may increase blood glucose concentrations, dosage adjustmentsof antidiabetic agents may be required.Corticosteroids may suppress reactions to skin tests.. Pregnancy. Teratogenic EffectsPregnancy Category CPrednisolone has been shown to be teratogenic in many species when given in dosesequivalent to the human dose. Animal studies in which prednisolone has been given topregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in theoffspring. There are no adequate and well controlled studies in pregnant women. PrednisoloneSodium Phosphate Oral Solution should be used during pregnancy only if the potential benefitjustifies the potential risk to the fetus. Infants born to mothers who have receivedcorticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.. Nursing Mothers. Systemically administered corticosteroids appear in human milk and could suppress growth,interfere with endogenous corticosteroid production, or cause other untoward effects.Caution should be exercised when Prednisolone Sodium Phosphate Oral Solution isadministered to nursing woman.. Pediatric Use. 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 adultpopulations. Published studies provide evidence of efficacy and safety in pediatric patientsfor the treatment of nephrotic syndrome (>2 years of age), and aggressive lymphomas andleukemias (>1 month of age). However, some of these conclusions and other indicationsfor pediatric use of corticosteroid, e.g., severe asthma and wheezing, are based on adequateand well-controlled trials conducted in adults, on the premises that the course of the diseasesand 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). Like adults, pediatric patients should be carefully observed withfrequent measurements of blood pressure, weight, height, intraocular pressure, and clinicalevaluation for the presence of infection, psychosocial disturbances, thromboembolism,peptic ulcers, cataracts, and osteoporosis.Children who are treated with corticosteroids by any route, including systemicallyadministered corticosteroids, may experience decrease in their growth velocity. Thisnegative impact of corticosteroids on growth has been observed at low systemic doses andin the absence of laboratory evidence of HPA axis suppression (i.e., cosyntropin stimulationand basal cortisol plasma levels). Growth velocity may therefore be more sensitive indicatorof systemic corticosteroid exposure in children than some commonly used tests of HPAaxis function. The linear growth of children treated with corticosteroids by any route shouldbe monitored, and the potential growth effects of prolonged treatment should be weighedagainst clinical benefits obtained and the availability of other treatment alternatives. In orderto minimize the potential growth effects of corticosteroids, children should be titrated to thelowest effective dose.. Geriatric Use. Clinical studies of Prednisolone Sodium Phosphate Oral Solution did not include sufficientnumbers of subjects aged 65 and over to determine whether they respond differently fromyounger subjects. Other reported clinical experience with prednisolone sodium phosphatehas not identified differences in responses between the elderly and younger patients.However, the incidence of corticosteroid-induced side effects may be increased in geriatricpatients and appear to be dose-related. Osteoporosis is the most frequently encounteredcomplication, which occurs at higher incidence rate in corticosteroid-treated geriatricpatients as compared to younger populations and in age-matched controls. Losses of bonemineral density appear to be greatest early on in the course of treatment and may recoverover time after steroid withdrawal or use of lower doses (i.e., <= mg/day). Prednisolonedoses of 7.5 mg/day or higher have been associated with an increased relative risk of bothvertebral and nonvertebral fractures, even in the presence of higher bone density comparedto patients with involutional osteoporosis.Routine screening of geriatric patients, including regular assessments of bone mineraldensity and institution of fracture prevention strategies, along with regular review ofprednisolone indication should be undertaken to minimize complications and keep theprednisolone dose at the lowest acceptable level. Co-administration of bisphosphonates hasbeen shown to retard the rate of bone loss in corticosteroid-treated males andpostmenopausal females, and these agents are recommended in the prevention andtreatment of corticosteroid-induced osteoporosis.It has been reported that equivalent weight-based doses yield higher total and unboundprednisolone plasma concentrations and reduced renal and non-renal clearance in elderlypatients compared to younger populations. However, it is not clear whether dosing reductionswould be necessary in elderly patients, since these pharmacokinetic alterations may be offsetby age-related differences in responsiveness of target organs and/or less pronouncedsuppression of adrenal release of cortisol. Dose selection for an elderly patient should becautious, usually starting at the low end of the dosing range, reflecting the greater frequency ofdecreased 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 reactionsto this drug may be greater in patients with impaired renal function. Because elderly patientsare more likely to have decreased renal function, care should be taken in dose selection,and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY).

WARNINGS SECTION.

WARNINGS. GeneralIn patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidlyacting corticosteroids before, during and after the stressful situation is indicated.Cardio-renalAverage and large doses of hydrocortisone or cortisone can cause elevation of bloodpressure, salt and water retention, and increased excretion of potassium. These effects areless likely to occur with the synthetic derivatives except when used in large doses. Dietarysalt restriction and potassium supplementation may be necessary. All corticosteroidsincrease calcium excretion.EndocrineCorticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppressionwith the potential for glucocorticosteroid insufficiency after withdrawal of treatment.Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increasedin hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustmentin dosage.Immunosuppression and Increased Risk of InfectionCorticosteroids, including Prednisolone Sodium Phosphate Oral Solution, suppress theimmune system and increase the risk of infection with any pathogen, including viral,bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can:o Reduce resistance to new infectionso Exacerbate existing infectionso Increase the risk of disseminated infectionso Increase the risk of reactivation or exacerbation of latent infectionso Mask some signs of infectionCorticosteroid-associated infections can be mild but can be severe and at times fatal. Therate of infectious complications increases with increasing corticosteroid dosages.Monitor for the development of infection and consider Prednisolone Sodium Phosphate OralSolution withdrawal or dosage reduction as needed.TuberculosisIf Prednisolone Sodium Phosphate Oral Solution is used to treat condition in patients withlatent tuberculosis or tuberculin reactivity, reactivation of the disease may occur. Closelymonitor such patients for reactivation. During prolonged Prednisolone Sodium PhosphateOral Solution therapy, patients with latent tuberculosis or tuberculin reactivity should receivechemoprophylaxis.Varicella Zoster and Measles Viral InfectionsVaricella and measles can have serious or even fatal course in non-immune patients takingcorticosteroids, including Prednisolone Sodium Phosphate Oral Solution. In corticosteroid-treated patients who have not had these diseases or are non-immune, particular care shouldbe taken to avoid exposure to varicella and measles:o If Prednisolone Sodium Phosphate Oral Solution-treated patient is exposed tovaricella, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated.If varicella develops, treatment with antiviral agents may be considered.oIf Prednisolone Sodium Phosphate Oral Solution-treated patient is exposed tomeasles, prophylaxis with immunoglobulin (IG) may be indicated.Hepatitis Virus ReactivationHepatitis virus reactivation can occur in patients who are hepatitis carriers treated withimmunosuppressive dosages of corticosteroids, including Prednisolone Sodium PhosphateOral Solution. Reactivation can also occur infrequently in corticosteroid-treated patients whoappear to have resolved hepatitis infection.Screen patients for hepatitis infection before initiating immunosuppressive (e.g.,prolonged) treatment with Prednisolone Sodium Phosphate Oral Solution. For patients whoshow evidence of hepatitis infection, recommend consultation with physicians withexpertise in managing hepatitis regarding monitoring and consideration for hepatitis Bantiviral therapy.Fungal InfectionsCorticosteroids, including Prednisolone Sodium Phosphate Oral Solution, may exacerbatesystemic fungal infections; therefore, avoid Prednisolone Sodium Phosphate Oral Solutionuse in the presence of such infections unless Prednisolone Sodium Phosphate Oral Solutionis needed to control drug reactions. For patients on chronic Prednisolone Sodium PhosphateOral Solution therapy who develop systemic fungal infections, Prednisolone SodiumPhosphate Oral Solution withdrawal or dosage reduction is recommended.AmebiasisCorticosteroids, including Prednisolone Sodium Phosphate Oral Solution, may activate latentamebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruledout before initiating Prednisolone Sodium Phosphate Oral Solution in patients who havespent time in the tropics or patients with unexplained diarrhea.Strongyloides InfestationCorticosteroids, including Prednisolone Sodium Phosphate Oral Solution, should be usedwith great care in patients with known or suspected Strongyloides (threadworm) infestation.In such patients, corticosteroid-induced immunosuppression may lead to Strongyloideshyperinfection and dissemination with widespread larval migration, often accompanied bysevere enterocolitis and potentially fatal gram-negative septicemia.Cerebral MalariaAvoid corticosteroids, including Prednisolone Sodium Phosphate Oral Solution, in patientswith cerebral malaria.Ophthalmic Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possibledamage to the optic nerves, and may enhance the establishment of secondary ocularinfections due to bacteria, fungi or viruses. The use of oral corticosteroids is notrecommended in the treatment of optic neuritis and may lead to an increase in the risk ofnew episodes. Corticosteroids should not be used in active ocular herpes simplex.Kaposis Sarcoma Kaposis sarcoma has been reported to occur in patients receiving corticosteroid therapy,most often for chronic conditions. Discontinuation of corticosteroids may result in clinicalimprovement of Kaposis sarcoma.VaccinationAdministration of live or live, attenuated vaccines is contraindicated in patients receivingimmunosuppressive doses of corticosteroids. Killed or inactivated vaccines may beadministered, however, the response to such vaccines cannot be predicted. Immunizationprocedures may be undertaken in patients who are receiving corticosteroids as replacementtherapy, e.g., for Addisons disease.