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    / Kamada


    Active Ingredient
    Prednisolone 1 mg/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Oral Solution

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    Dosage

    The lowest dosage that will produce an acceptable result should be used; when it is possible to reduce the dosage, this must be accomplished by stages.
    During prolonged therapy any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy they may need to be temporarily re-introduced.
    The medicinal product should preferably be taken as a single dose in the morning. However, divided daily dosages may be employed if required.
    Adults: The dose used will depend upon the disease, its severity, and the clinical response obtained.
    Short-term treatment: 20 to 30 mg daily for the first few days, subsequently reducing the daily dosage by 2.5 or 5 mg every two to five days, depending upon the response.
    Rheumatoid arthritis: 7.5 to 10 mg daily. For maintenance therapy the lowest effective dosage is used.
    Children: Fractions of the adult dosage may be used (e.g. 75% at 12 years, 50% at 7 years and 25% at 1 year) but clinical factors must be given due weight.
    For treatment of bronchial asthma:
    Children under 2 years: up to 10 mg daily.
    Children 2-5 years inclusive: up to 20 mg daily.
    Children older than 5 years: 30 mg daily or more (up to 40 mg daily) may be used. To reduce the risk of dosing errors, should the doctor prescribe more than 30 mg daily, a more appropriate prednisolone presentation (e.g. high dosage tablets) should be used.
    Corticosteroids cause growth retardation in infancy, childhood and adolescence which may be irreversible. Treatment should be limited to the minimum dosage for the shortest possible time. In order to minimise suppression of the hypothalamo-pituitary adrenal axis and growth retardation, treatment should be administered where possible as a single dose on alternate days.
    See prescribing information for full details.


    Indications

    * Rheumatological disorders and connective tissue diseases:
    – Rheumatoid arthritis (for primary chronic disease and maintenance therapy)
    – Systemic lupus erythematosus (non-organ threatening disease)
    – Mild-moderate juvenile dermatomyositis
    * Severe or debilitating allergic conditions, not treatable in a conventional manner
    * Bronchial asthma in children
    * Bronchial asthma in adults (for maintenance therapy)
    * Sarcoidosis in children and for maintenance therapy in adults
    * Acquired haemolytic anaemia (autoimmune, for maintenance therapy)


    Contra-Indications

    * Hypersensitivity to the active substance or to any of the excipients
    * Tuberculosis, peptic ulcer, psychosis, ocular herpes simplex. Tropical worm infections, systemic infections including fungal infections, unless specific anti-infective therapy is employed. Live virus immunization.


    Special Precautions

    * Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment. Withdrawal of corticosteroids after prolonged therapy must therefore always be gradual to avoid acute adrenal insufficiency, being tapered off over weeks or months according to the dose and duration of treatment.
    * Suppression of the HPA axis and other undesirable effects may be minimized by using the lowest effective dose for the minimum period, and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternate days. Frequent patient review is required to appropriately titrate the dose against disease activity.
    * Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognized.
    * Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. Passive immunization with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment.
    * Should avoid exposure to measles and to seek immediate advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.
    * Live vaccines should not be given with impaired immune responsiveness caused by high doses of corticosteroids.
    * Kaposi’s sarcoma has been reported. Discontinuation of corticosteroids may result in clinical remission.
    * Fluid retention is possible, care must be taken in patients with renal insufficiency or hypertension or congestive heart failure.
    * Corticosteroids may worsen diabetes mellitus, osteoporosis, hypertension, glaucoma and epilepsy and therefore patients with these conditions or a family history of them should be monitored frequently.
    * Care is required and frequent patient monitoring necessary where there is a history of severe affective disorders (especially a previous history of steroid psychosis), previous steroid myopathy, peptic ulceration, hypothyroidism, recent myocardial infarction or patients with a history of tuberculosis.
    * In patients with liver failure, blood levels of corticosteroid may be increased, as with other drugs which are metabolized in the liver. Frequent patient monitoring is therefore necessary.
    * Precipitate porphyria
    * Reversible Steven-Johnson-Syndrome (SJS)
    * At high doses, sufficient calcium intake and sodium restriction, as well as potassium levels should be monitored.
    * Visual disturbance:
    – Appearance of symptoms such as blurred vision, or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma, or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
    – Chorioretinopathy may result in impaired vision, including loss of vision.
    – Regular checkups with doctors (including vision checkups in three month-intervals) are advised during long term treatment.
    * Scleroderma renal crisis: Caution is required in patients with systemic sclerosis because of an increased incidence of (possibly fatal) scleroderma renal crisis with hypertension and decreased urinary output observed with a daily dose of 15 mg or more prednisolone. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.
    * Use in Children: Corticosteroids cause dose-related growth retardation in infancy, childhood and adolescence, which may be irreversible.
    * Use in the Elderly: The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.
    * Potentially severe psychiatric adverse reactions may occur with systemic steroids. Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure, although dose levels do not allow prediction of the onset, type, severity or duration of reactions.
    * Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
    * Withdrawal: In patients who have received more than physiological doses of systemic corticosteroids (approximately 7.5 mg prednisolone or equivalent) for greater than 3 weeks, withdrawal should not be abrupt. How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. Clinical assessment of disease activity may be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses. Once a daily dose equivalent to 7.5mg of prednisolone is reached, dose reduction should be slower to allow the HPA-axis to recover.
    Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it is considered that the disease is unlikely to relapse. Abrupt withdrawal of doses of up to 40mg daily of prednisolone, or equivalent for 3 weeks is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of patients. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting 3 weeks or less:
    – Patients who have had repeated courses of systemic corticosteroids, particularly if taken for greater than 3 weeks,
    – When a short course has been prescribed within one year of cessation of long-term therapy (months or years),
    – Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy,
    – Patients receiving doses of systemic corticosteroid greater than 40mg daily of prednisolone,
    – Patients repeatedly taking doses in the evening.
    * During prolonged therapy any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy they may need to be temporarily reintroduced.
    See prescribing information for full details.


    Side Effects

    The incidence of predictable undesirable effects, including hypothalamo-pituitary-adrenal (HPA) suppression, correlates with the relative potency of the drug, dosage, timing of administration and the duration of treatment.
    See prescribing information for full details.


    Drug interactions

    * Rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone, ephedrine and aminoglutethimide enhance the metabolism of corticosteroids and its therapeutic effects may be reduced. Therefore it may be necessary to adjust the dose accordingly.
    * Mifepristone may reduce the effect of corticosteroids for 3-4 days.
    * Erythromycin and ketoconazole may inhibit the metabolism of some corticosteroids.
    * Ciclosporin, ritonavir increases plasma concentration of prednisolone.
    * Oestrogens and other oral contraceptives may potentiate the effects of glucocorticoids and dosage adjustments may be required if oral contraceptives are added to or withdrawn from a stable dosage regimen.
    * The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonized by corticosteroids.
    * The growth promoting effect of somatotropin may be inhibited by the concomitant use of corticosteroids.
    * Steroids may reduce the effects of anticholinesterases in myasthenia gravis and cholecystographic x-ray media.
    * The efficacy of coumarin anticoagulants and warfarin may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.
    * Concomitant use of aspirin and Non Steroidal Anti-Inflammatory Drugs (NSAIDs) with corticosteroids increases the risk of gastro-intestinal bleeding and ulceration.
    * The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.
    * The hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics, and carbenoxolone, are enhanced by corticosteroids. The risk of hypokalaemia is increased with theophylline and amphotericin. Corticosteroids should not be given concomitantly with amphotericin, unless required to control reactions. The risk of hypokalaemia also increases if high doses of corticosteroids are given with high doses of bambuterol, fenoterol, formoterol, ritodrine, salbutamol, salmeterol and terbutaline. The toxicity of cardiac glycosides is increased if hypokalaemia occurs with corticosteroids.
    * Concomitant use with methotrexate may increase the risk of haematological toxicity.
    * High doses of corticosteroids impair the immune response and so live vaccines should be avoided
    * In rare cases the concomitant treatment with corticosteroids and fluoroquinolones may increase the risk of tendon rupture.
    * Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy:
    The ability of glucocorticoids to cross placenta varies between individual drugs, however, 88% of prednisolone is inactivated as it crosses the placenta.
    Glucocorticoids caused cleft palate formation in animal experiments. There is an ongoing discussion on the possibility of an increased risk of oral cleft formation in the human fetus as a result of the administration of glucocorticoids during the first trimester.
    If glucocorticoids are administered towards the end of pregnancy, there is a risk of atrophy of the fetal adrenal cortex, which may necessitate replacement therapy in the newborn, which has to be slowly reduced.
    During pregnancy, prednisolone oral solution should only be prescribed when the benefits to the mother and child outweigh the risks. The lowest effective dose of prednisolone oral solution needed to maintain adequate disease control should be used. Patients with pre-eclampsia or fluid retention require close monitoring.
    Lactation:
    Glucocorticoids are excreted in small amounts in breast milk (up to 0.23% of an individual dose). However doses of up to 40mg daily of prednisolone are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this may have a degree of adrenal suppression but the benefits of breast feeding are likely to outweigh any theoretical risk.
    The milk/plasma concentration ratio increases with increasing doses (e.g. 25% of the serum concentration are found in the breast milk with 80 mg prednisolone daily). Therefore, when high doses of prednisolone are given, it is recommended to avoid breastfeeding for 4 h after a dose.
    Fertility
    After high prednisolone doses (30 mg/day for at least 4 weeks) reversible disturbances of spermatogenesis has been observed, which lasted for several months after stop taking the medicine.


    Overdose

    Treatment is unlikely to be needed in cases of acute over dosage.
    Should alterations of the electrolytic balance occur within prolonged therapy at high doses, it would be appropriate to adjust the intake of sodium and potassium. Corticosteroids increase the urinary excretion of calcium.
    In case of overdose, the clinical control of patient’s vital functions, jointly with the common measures for elimination of the non-absorbed drug (gastric lavage, vegetal charcoal etc), are recommended.


    Manufacturer
    GENETIC S.P.A., ITALY
    Licence holder
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