COMPOSITION:

Each 1ml Predinisolone Domina contains 6.7mg Prednisolone Sodium Phosphate, equivalent to 5mg Prednisolone Base..

PHARMACODYNAMIC EFFECTS:

Naturally occurring glucocorticoids (hydrocortisone) are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Prednisolone is a synthetic adrenocortical steroid drug with predominantly glucocorticoid properties

PHARMACOKINETICS:

Absorption: Prednisolone is rapidly and well absorbed from the gastrointestinal tract following oral administration. Oral Solution produces a 14% higher peak plasma level of prednisolone than that seen with tablets.

Metabolism: Prednisolone is mainly metabolised in the liver

Excretion: it is eliminated from the plasma with a half-life of 2 to 4 hours and it is excreted in the urine as free and conjugated metabolites,

INDICATIONS:

Prednisolone is indicated in the following conditions:

1. Allergic states: Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in adult and pediatric populations with: seasonal or perennial allergic rhinitis; asthma; contact dermatitis; atopic dermatitis; serum sickness; drug hypersensitivity reactions.
2. Dermatologic Diseases: Pemphigus; bullous dermatitis herpetiformis; severe erythema multiforme (Stevens-Johnson syndrome); exfoliative erythroderma; mycosis fungoides.
3. Edematous States: To induce diuresis or remission of proteinuria in nephrotic syndrome in adults with lupus erythematosus 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 first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance); congenital adrenal hyperplasia; hypercalcemia associated with cancer; nonsuppurative thyroiditis.
5. Gastrointestinal Diseases: To tide the patient over a 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; temporal arteritis; sympathetic ophthalmia.
10. Respiratory Diseases: Symptomatic sarcoidosis; idiopathic eosinophilic pneumonias; fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate anti-tuberculous chemotherapy; asthma, hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, acute exacerbations of chronic obstructive pulmonary disease (COPD), and Pneumocystis carinii pneumonia (PCP) associated with hypoxemia occurring in an HIV individual who is also under treatment with appropriate anti-PCP antibiotics. Studies support the efficacy of systemic corticosteroids for the treatment of these conditions: allergic bronchopulmonary aspergillosis, idiopathic bronchiolitis obliterans with organizing pneumonia.
11. Rheumatic Disorders: As adjunctive therapy for short term administration (to tide the patient over an acute episode or exacerbation) in: psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (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, Sjogren's syndrome, relapsing polychondritis, and certain cases of vasculitis.
12. Miscellaneous: Tuberculous meningitis with subarachnoid block or impending block, tuberculosis with enlarged mediastinal lymph nodes causing respiratory difficulty, and tuberculosis with pleural or pericardial effusion (appropriate anti-tuberculous chemotherapy must be used concurrently when treating any tuberculosis complications); Trichinosis with neurologic or myocardial involvement; acute or chronic solid organ rejection (with or without other agents).

CONTRAINDICATIONS:

      Systemic fungal infections.

      Hypersensitivity to the drug or any of its components.

WARNINGS:

• General: In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during and after the stressful situation is indicated. Kaposi'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.
• Cardio-renal: Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. 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. All corticosteroids increase calcium excretion.
• Endocrine: Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with potential for glucocorticosteroid insufficiency after withdrawal of treatment. 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.

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.

• Infections: Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Corticosteroids may also mask some signs of infection. Chicken pox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure.
• Ophthalmic: 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 bacteria, 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. Corticosteroids should not be used in active ocular herpes simplex. Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.
• Latent diseases may be activated or there may be an exacerbation of intercurrent infections due to pathogens, Corticosteroids may activate latent amebiasis, Corticosteroids should not be used in cerebral malaria.
• Tuberculosis: The use of prednisolone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur.
• 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
• Neuro-psychiatric: 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. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Clinical improvement or recovery after stopping corticosteroids may require weeks to years. Psychic derangements may appear when corticosteroids are used. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.
• Musculoskeletal: Corticosteroids decrease bone formation and increase bone resorption with other factors it 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 before initiating corticosteroid therapy.
• Gastrointestinal: Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess or other pyogenic infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic ulcer.

Drug interactions:

• Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic drug metabolizing enzyme activity may enhance metabolism of prednisolone and require that the dosage of Prednisolone Oral Solution be increased.
• Increased activity of both cyclosporin and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.
• Estrogens may decrease the hepatic metabolism of certain corticosteroids thereby increasing their effect.
• Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects.
• Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin; therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.
• 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.
• When corticosteroids are administered concomitantly with potassium-depleting agents (i.e., diuretics, amphotericin-B), patients should be observed closely for development of hypokalemia. Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.
• 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.
• Corticosteroids may increase blood glucose concentrations; therefore dosage adjustments of antidiabetic agents may be required.
• Corticosteroids may suppress reactions to skin tests

PREGNANCY AND LACTATION:

Pregnancy: Teratogenic Effects: Category C: There are no adequate and well controlled studies in pregnant women. Prednisolone Oral Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Lactation: Systemically administered corticosteroids appear in human milk and could suppress growth. Caution should be exercised when Prednisolone Oral Solution is administer ed to a nursing woman.

Geriatric Use:

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

Pediatric Use:

Children, who are treated with corticosteroids by any route, may experience a decrease in their growth velocity. 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.

ADVERSE REACTIONS:

Cardiovascular: Hypertrophic cardiomyopathy in premature infants.

Dermatologic: Facial erythema; increased sweating; impaired wound healing.

Endocrine: Decreased carbohydrate tolerance; development of cushingoid state; hirsutism; increased requirements for insulin or oral hypoglycemic agents in diabetic patients; manifestations of latent diabetes mellitus; menstrual irregularities; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress; suppression of growth in children.

Fluid and Electrolyte Disturbances: Congestive heart failure in susceptible patients; fluid retention; hypertension; hypokalemic alkalosis; potassium loss; sodium retention.

Gastrointestinal: Abdominal distention; elevation in serum liver enzyme levels (usually reversible upon discontinuation); pancreatitis; peptic ulcer with possible perforation and hemorrhage; ulcerative esophagitis.

Metabolic: Negative nitrogen balance due to protein catabolism.

Musculoskeletal: Aseptic necrosis of femoral and humeral heads; loss of muscle mass; muscle weakness; osteoporosis; pathologic fracture of long bones; steroid myopathy; tendon rupture; vertebral compression fractures.

Neurological: Convulsions; headache; increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment; psychic disorders; vertigo.

Ophthalmic: Exophthalmos; glaucoma; increased intraocular pressure; posterior subcapsular cataracts.

Other: Increased appetite; malaise; nausea; weight gain.

DOSAGE AND ADMINISTRATION:

• The initial dosage of Prednisolone Oral Solution may vary from (5 to 60 mg prednisolone base) per day depending on the specific disease 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, Prednisolone should be discontinued and the patient placed on other appropriate therapy.
• 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 which 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.
• If after long term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
• 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 or 4 to 8 mg dexamethasone every other day for one month have been shown to be effective.
• In pediatric patients, the initial dose of Prednisolone Oral Solution may vary depending on the specific disease 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/m² bsa/day).
• 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.
• The recommended dosing for systemic prednisolone 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%. 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.

OVERDOSAGE:

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.