Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Medrone is indicated for conditions requiring glucocorticoid activity such as:

1. Endocrine disorders Primary and secondary adrenal insufficiency Congenital adrenal hyperplasia

2. Rheumatic disorders Rheumatoid arthritis Juvenile chronic arthritis Ankylosing spondylitis

3. Collagen diseases/arteritis Systemic lupus erythematosus Systemic dermatomyositis (polymyositis) Rheumatic fever with severe carditis Giant cell arteritis/polymyalgia rheumatica

4. Dermatological diseases Pemphigus vulgaris

5. Allergic states Severe seasonal and perennial allergic rhinitis Drug hypersensitivity reactions Serum sickness Allergic contact dermatitis Bronchial asthma

6. Ophthalmic diseases Anterior uveitis (iritis, iridocyclitis) Posterior uveitis Optic neuritis

7. Respiratory diseases Pulmonary sarcoid Fulminating or disseminated tuberculosis (with appropriate antituberculous chemotherapy) Aspiration of gastric contents

8. Haematological disorders Idiopathic thrombocytopenic purpura Haemolytic anaemia (autoimmune)

9. Neoplastic diseases Leukaemia (acute and lymphatic) Malignant lymphoma

10. Gastrointestinal diseases Ulcerative colitis Crohn's disease

11. Miscellaneous Tuberculous meningitis (with appropriate anti-tuberculous chemotherapy) Transplantation

Adult Dosage

The dosage recommendations shown in the table below are suggested initial daily doses and are intended as guides. The average total daily dose recommended may be given either as a single dose or in divided doses (excepting in alternate day therapy when the minimum effective daily dose is doubled and given every other day at 8.00 am).

Undesirable effects may be minimised by using the lowest effective dose for the minimum period (see Special warnings and special precautions for use).

The initial suppressive dose level may vary depending on the condition being treated. This is continued until a satisfactory clinical response is obtained, a period usually of three to seven days in the case of rheumatic diseases (except for acute rheumatic carditis), allergic conditions affecting the skin or respiratory tract and ophthalmic diseases. If a satisfactory response is not obtained in seven days, reevaluation of the case to confirm the original diagnosis should be made. As soon as a satisfactory clinical response is obtained, the daily dose should be reduced gradually, either to termination of treatment in the case of acute conditions (e.g. seasonal asthma, exfoliative dermatitis, acute ocular inflammations) or to the minimal effective maintenance dose level in the case of chronic conditions (e.g. rheumatoid arthritis, systemic lupus erythematosus, bronchial asthma, atopic dermatitis). In chronic conditions, and in rheumatoid arthritis especially, it is important that the reduction in dosage from initial to maintenance dose levels be accomplished as clinically appropriate. Decrements of not more than 2 mg at intervals of 7 10 days are suggested. In rheumatoid arthritis, maintenance steroid therapy should be at the lowest possible level.

In alternateday therapy, the minimum daily corticoid requirement is doubled and administered as a single dose every other day at 8.00 am. Dosage requirements depend on the condition being treated and response of the patient.

Dosage Recommendations:

Indications	Recommended initial daily dosage
Rheumatoid arthritis
severe	12 – 16 mg
moderately severe	8 – 12 mg
moderate	4 – 8 mg
children	4 8 mg
Systemic dermatomyositis	48 mg
Systemic lupus erythematosus	20 100 mg
Acute rheumatic fever	48 mg until ESR normal for one week.
Allergic diseases	12 40 mg
Bronchial asthma	up to 64 mg single dose/alternate day up to 100 mg maximum.
Ophthalmic diseases	12 40 mg
Haematological disorders and leukaemias	16 100 mg
Malignant lymphoma	16 - 100 mg
Ulcerative colitis	16 60 mg
Crohn's disease<	up to 48 mg per day in acute episodes.
Organ transplantation	up to 3.6 mg/kg/day
Pulmonary sarcoid	32 48 mg on alternate days.
Giant cell arteritis/polymyalgia rheumatica	64 mg
Pemphigus vulgaris	80 360 mg

Child Dosage

 In general, dosage for children should be based upon clinical response and is at the discretion of the physician. Treatment should be limited to the minimum dosage for the shortest period of time. If possible, treatment should be administered as a single dose on alternate days (see Special warnings and special precautions for use).

Elderly Dosage

Treatment of elderly patients, particularly if longterm, should be planned bearing in mind the more serious consequences of the common sideeffects of corticosteroids in old age, particularly osteoporosis, diabetes, hypertension, susceptibility to infection and thinning of skin (see Special warnings and special precautions for use).

Contra Indications

Medrone is contraindicated where there is known hypersensitivity to components and in systemic infection unless specific anti-infective therapy is employed.

Special Precautions

Warnings and precautions:

1. A Patient Information Leaflet is provided in the pack by the manufacturer.

2. 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 or whenever possible as a single morning dose on alternative days. Frequent patient review is required to appropriately titrate the dose against disease activity (see Posology and method of administration).

3. Adrenal cortical atrophy develops during prolonged therapy and may persist for months after stopping treatment. In patients who have received more than physiological doses of systemic corticosteroids (approximately 6 mg methylprednisolone) 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 of 6 mg methylprednisolone 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 considered that the disease is unlikely to relapse. Abrupt withdrawal of doses up to 32 mg daily of methylprednisolone 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 32 mg daily of methylprednisolone.

• Patients repeatedly taking doses in the evening.

4. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

5. Patients should carry 'Steroid Treatment' cards which give clear guidance on the precautions to be taken to minimise risk and which provide details of prescriber, drug, dosage and the duration of treatment.

6. Corticosteroids may mask some signs of infection, and new infections may appear during their use. Suppression of the inflammatory response and immune function increases the susceptibility to fungal, viral and bacterial infections and their severity. The clinical presentation may often be atypical and may reach an advanced stage before being recognised.

7. Chickenpox is of serious concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) 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. Corticosteroids should not be stopped and the dose may need to be increased.

8. Exposure to measles should be avoided. Medical advice must be sought immediately if exposure occurs. Prophylaxis with normal intramuscular immunoglobulin may be needed.

9. Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.

10. The use of Medrone 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. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

11. Care should be taken for patients receiving cardioactive drugs such as digoxin because of steroid induced electrolyte disturbance/potassium loss (see Undesirable effects).

Special precautions:

Particular care is required when considering the use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.

1. Osteoporosis (post-menopausal females are particularly at risk).

2. Hypertension or congestive heart failure.

3. Existing or previous history of severe affective disorders (especially previous steroid psychosis).

4. Diabetes mellitus (or a family history of diabetes).

5. History of tuberculosis.

6. Glaucoma (or a family history of glaucoma).

7. Previous corticosteroid-induced myopathy.

8. Liver failure or cirrhosis.

9. Renal insufficiency.

10. Epilepsy.

11. Peptic ulceration.

12. Fresh intestinal anastomoses.

13. Predisposition to thrombophlebitis.

14. Abscess or other pyogenic infections.

15. Ulcerative colitis.

16. Diverticulitis.

17. Myasthenia gravis.

18. Ocular herpes simplex, for fear of corneal perforation.

19. Hypothyroidism.

20. Recent myocardial infarction (myocardial rupture has been reported).

21. Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.

22. Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids. Symptoms typically emerge within a few days or weeks of starting 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. 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 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.

Use in children: Corticosteroids cause growth retardation in infancy, childhood and adolescence. Treatment should be limited to the minimum dosage for the shortest possible time. In order to minimise suppression of the hypothalamopituitary-adrenal axis and growth retardation, treatment should be administered where possible as a single dose on alternate days.

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.

Interactions

1. Convulsions have been reported with concurrent use of methylprednisolone and ciclosporin. Since concurrent administration of these agents results in a mutual inhibition of metabolism, it is possible that convulsions and other adverse effects associated with the individual use of either drug may be more apt to occur.

2. Drugs that induce hepatic enzymes, such as rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone, and aminoglutethimide enhance the metabolism of corticosteroids and its therapeutic effects may be reduced.

3. Drugs which inhibit the CYP3A4 enzyme, such as cimetidine, erythromycin, ketoconazole, itraconazole, diltiazem and mibefradil, may decrease the rate of metabolism of corticosteroids and hence increase the serum concentration.

4. Steroids may reduce the effects of anticholinesterases in myasthenia gravis. The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids, and the hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced.

5. The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.

6. The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication. Salicylates and non-steroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids in hypothrombinaemia.

7. Steroids have been reported to interact with neuromuscular blocking agents such as pancuronium with partial reversal of the neuromuscular block.

Adverse Reactions

The incidence of predictable undesirable sideeffects associated with the use of corticosteroids, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and duration of treatment (see Special warnings and special precautions for use).

GASTRO-INTESTINAL Dyspepsia, peptic ulceration with perforation and haemorrhage, abdominal distension, oesophageal ulceration, oesophageal candidiasis, acute pancreatitis, perforation of bowel, gastric haemorrhage.

Increases in alanine transaminase (ALT, SGPT) aspartate transaminase (AST, SGOT) and alkaline phosphatase have been observed following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome and are reversible upon discontinuation.

ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE EFFECTS - Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, may suppress reactions to skin tests, recurrence of dormant tuberculosis (see Special warnings and special precautions for use).

MUSCULOSKELETAL Proximal myopathy, osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture, muscle weakness.

FLUID AND ELECTROLYTE DISTURBANCE Sodium and water retention, hypertension, hypokalaemic alkalosis, potassium loss, congestive heart failure in susceptible patients.

DERMATOLOGICAL Impaired healing, skin atrophy, bruising, striae, telangiectasia, acne, petechiae and ecchymosis. Kaposi's sarcoma has been reported in patients receiving corticosteroid therapy.

ENDOCRINE/METABOLIC Suppression of the hypothalamopituitary-adrenal axis, growth suppression in infancy, childhood and adolescence; menstrual irregularity and amenorrhoea. Cushingoid facies, hirsutism, weight gain, impaired carbohydrate tolerance with increased requirement for antidiabetic therapy, negative nitrogen and calcium balance. Increased appetite.

NEUROPSYCHIATRIC A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood psychological dependence and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, seizures and cognitive dysfunction including confusion and amnesia have been reported for all corticosteroids. . Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions was estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown. Increased intra-cranial pressure with papilloedema in children (pseudotumour cerebri) has been reported, usually after treatment withdrawal of methylprednisolone.

OPHTHALMIC Increased intraocular pressure, glaucoma, papilloedema with possible damage to the optic nerve, cataracts, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal disease, exophthalmos.

CARDIOVASCULAR – Myocardial rupture following myocardial infarction.

GENERAL Leucocytosis, hypersensitivity reactions including anaphylaxis, thrombo-embolism, nausea, malaise, persistent hiccups with high doses of corticosteroids.

WITHDRAWAL SYMPTOMS Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death (see Special warnings and special precautions for use).

A 'withdrawal syndrome' may also occur including, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.

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