PREDNISOLONE

The initial dosage of Deltacortril Gastro-resistant Tablets may vary from 5mg to 60mg daily depending on the disorder being treated. Divided daily dosage is usually used. The following therapeutic guidelines should be kept in mind for all therapy with corticosteroids: Corticosteroids are palliative symptomatic treatment by virtue of their anti- inflammatory effects; they are never curative.

The appropriate individual dose must be determined by trial and error and must be re- evaluated regularly according to activity of the disease. As corticosteroid therapy becomes prolonged and as the dose is increased, the incidence of disabling side-effects increases.

In general, initial dosage shall be maintained or adjusted until the anticipated response is observed. The dose should be gradually reduced until the lowest dose which will maintain an adequate clinical response is reached. 4 'Special warnings and special precautions for use').

5mg 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 hypothalamic-pituitary-adrenal (HPA) suppression, the dose of corticosteroid may be reduced rapidly to physiological doses.

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 (or equivalent).

• patients repeatedly taking doses in the evening. 4 'Special warnings and special precautions for use') If there is lack of a satisfactory clinical response to Gastro-resistant Tablets, the drug should be gradually discontinued and the patient transferred to alternative therapy.

Intermittent dosage regimen A single dose of Gastro-resistant Tablets in the morning on alternate days or at longer intervals is acceptable therapy for some patients. When this regimen is practical, the degree of pituitary-adrenal suppression can be minimised.

Specific dosage guidelines The following recommendations for some corticosteroid- responsive disorders are for guidance only. Acute or severe disease may require initial high dose therapy with reduction to the lowest effective maintenance dose as soon as possible.

5mg daily during chronic treatment. Allergic and skin disorders Initial doses of 5-15mg daily are commonly adequate. Collagenosis Initial doses of 20-30mg daily are frequently effective. Those with more severe symptoms may require higher doses.

Rheumatoid arthritis The usual initial dose is 10-15mg daily. The lowest daily maintenance dose compatible with tolerable symptomatic relief is recommended. Blood disorders and lymphoma An initial daily dose of 15-60mg is often necessary with reduction after an adequate clinical or haematological response.

Higher doses may be necessary to induce remission in acute leukaemia. Special populations Use in elderly Treatment of elderly patients, particularly if long-term, should be planned bearing in mind the more serious consequences of the common side-effects of corticosteroids in old age (see also 'Special warnings and special precautions for use').

8 ‘Undesirable effects’). Alternate day dosage is preferable where possible.

). Symptoms typically emerge within a few days or weeks of starting the treatment. 5 Interaction with other medicinal products and other forms of interaction), although dose levels do not allow prediction of the onset, type, severity or duration of reactions.

Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected.

Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/ withdrawal of systemic steroids, although such reactions have been reported infrequently. Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives.

These would include depressive or manic-depressive illness and previous steroid psychosis. 5 Interaction with other medicinal products and other forms of interaction). 8 Undesirable effects). Although calciphylaxis is most commonly observed in patients who have end stage kidney failure, it has also been reported in patients taking corticosteroids who have minimal or no renal impairment and normal calcium, phosphate and parathyroid hormone levels.

Patients/carers should be advised to seek medical advice if symptoms develop. Caution is necessary when oral corticosteroids, including Deltacortril Gastro-resistant Tablets, are prescribed in patients with the following conditions, and frequent patient monitoring is necessary.

- Tuberculosis: Those with a previous history of, or X-ray changes characteristic of, tuberculosis. The emergence of active tuberculosis can, however, be prevented by the prophylactic use of anti-tuberculosis therapy. - Inflammatory bowel disease: Symptoms recurred in a patient with Crohn’s disease on changing from conventional to enteric-coated tablets of prednisolone.

This was not an isolated occurrence in the author’s unit, and it was advocated that only non-enteric coated prednisolone tablets should be used in Crohn’s disease, and that the enteric coated form should be used with caution in any condition characterized by diarrhoea or a rapid transit time.

- Hypertension. - Congestive heart failure. - Liver failure. - Hepatic disease: In patients with acute and active hepatitis, protein binding of the glucocorticoids will be reduced and peak concentrations of administered glucocorticoids increased.

Elimination of prednisolone will also be impaired. There is an enhanced effect of corticosteroids in patients with cirrhosis. - Renal insufficiency. - Diabetes mellitus or in those with a family history of diabetes. - Osteoporosis: This is of special importance in post-menopausal females who are at particular risk.

- Corticosteroid requirements may be reduced in menopausal and post-menopausal women. - Patients with a history of severe affective disorders and particularly those with a previous history of steroid-induced psychoses. - Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids including prednisolone.

- Epilepsy, and/or seizure disorders - Peptic ulceration. - Previous steroid myopathy. - Glucocorticoids should be used cautiously in patients with myasthenia gravis receiving anticholinesterase therapy. - Because cortisone has been reported rarely to increase blood coagulability and to precipitate intravascular thrombosis, thromboembolism, and thrombophlebitis, corticosteroids should be used with caution in patients with thromboembolic disorders.

- Duchenne’s muscular dystrophy: transient rhabdomyolysis and myoglobinuria may occur following strenuous physical activity. It is not known whether this is due to prednisolone itself or the increased physical activity. Undesirable effects may be minimised by using the lowest effective dose for the minimum period and by administering the daily requirement as a single morning dose on alternate days.

2 'Posology and method of administration'). Adrenocortical Insufficiency Pharmacologic doses of corticosteroids administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression (secondary adrenocortical insufficiency).

The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose, frequency, time of administration, and duration of glucocorticoid therapy. In addition, acute adrenal insufficiency leading to a fatal outcome may occur if glucocorticoids are withdrawn abruptly.

Drug-induced secondary adrenocortical insufficiency may therefore 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. 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.

Patients should carry “Steroid treatment” cards which give clear guidance on the precautions […]

8 Undesirable effects). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/ systemic exposure (see also Section

1 List of Excipients). • Systemic infections unless specific anti-infective therapy is employed. • Ocular herpes simplex because of possible perforation. • Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.