Stadsone 4

Rx

Indications

Endocrine disorders

• Primary or secondary adrenocortical insufficiency
• Congenital adrenal hyperplasia.
• Nonsuppurative thyroiditis.
• Hypercalcaemia associated with cancer.

Non-endocrine disorders

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.
• Post-traumatic osteoarthritis.
• Synovitis of osteoarthritis.
• Epicondylitis.

Collagen diseases

During an exacerbation or as maintenance therapy in selected cases of:

• Systemic lupus erythematosus.
• Systemic dermatomyositis (polymyositis).
• Acute rheumatic carditis.
• Polymyalgia rheumatica.
• Giant cell arteritis.

Dermatologic diseases

• Pemphigus.
• Bullous dermatitis herpetiformis.
• Severe erythema multiforme (Stevens-Johnson syndrome).
• Exfoliative dermatitis.
• Mycosis fungoides.
• Severe psoriasis.
• Severe seborrhoeic dermatitis.

Allergic states

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment:

• Seasonal or perennial allergic rhinitis.
• Serum sickness.
• Bronchial asthma.
• Drug hypersensitivity reactions.
• Contact dermatitis.
• Atopic dermatitis.

Ophthalmic diseases

Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as:

• Allergic corneal marginal ulcers.
• Herpes zoster ophthalmicus.
• Anterior segment inflammation.
• Diffuse posterior uveitis and choroiditis.
• Sympathetic ophthalmia.
• Allergic conjunctivitis.
• Keratitis.
• Chorioretinitis.
• Optic neuritis.
• Iritis and iridocyclitis.

Respiratory diseases

• Symptomatic sarcoidosis.
• Loeffler’s syndrome not manageable by other means.
• Berylliosis.
• Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy.
• Aspiration pneumonitis.

Haematologic disorders

• Idiopathic thrombocytopenia purpura in adults.
• Secondary thrombocytopenia in adults.
• Acquired (autoimmune) haemolytic anaemia.
• Erythroblastopenia (RBC anaemia).
• Congenital (erythroid) hypoplastic anaemia.

Neoplastic diseases

For palliative management of:

• Leukemias and lymphomas in adults.
• Acute leukaemia of childhood.

Edematous states

• To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uraemia, of the idiopathic type or that due to lupus erythematosus.

Gastrointestinal diseases

To tide the patient over a critical period of the disease in:

• Ulcerative colitis.
• Regional enteritis.

Nervous system

• Acute exacerbations of multiple sclerosis.
• Management of oedema associated with brain tumour.

Organ transplantations

Miscellaneous

• Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.
• Trichinosis with neurologic or myocardial involvement.

Dosage

• The initial dosage of methylprednisolone tablets may vary depending on the specific disease entity being treated. In situations of less severity lower doses will generally suffice, while in selected patients, higher initial doses may be required. Clinical situations in which high dose therapy may be indicated include multiple sclerosis (200 mg/day), cerebral oedema (200 – 1,000 mg/day) and organ transplantation (up to 7 mg/kg/day). If, after a reasonable period of time, there is a lack of satisfactory clinical response, methylprednisolone should be discontinued and the patient transferred to other appropriate therapy. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
• After a favourable 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 are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation (stressful situations not directly related to the disease entity under treatment) it may be necessary to increase the dosage of methylprednisolone for a period of time consistent with the patient’s condition.
• It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient.
• Alternate day therapy (ADT): Alternate day therapy is a corticosteroid dosing regimen in which twice the usual daily dose of corticosteroid is administered every other morning. The purpose of this mode of therapy is to provide a patient requiring long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimising certain undesirable effects, including pituitary-adrenal suppression, the Cushingoid state, corticoid withdrawal symptoms and growth suppression in children.
• Elderly patients: 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, particularly osteoporosis, diabetes, hypertension, susceptibility to infection and thinning of skin.
• Paediatric population: 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.

Usage

Stadsone 4 is orally administered.

• In patients who have systemic fungal infections.
• In patients who have systemic infections unless specific anti-infective therapy is employed.
• In patients who have hypersensitivity to the active substance or to any of the excipients.
• Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Common

• Infection (including increased susceptibility and severity of infections with suppression of clinical symptoms and signs).
• Cushingoid.
• Sodium retention, fluid retention.
• Affective disorder (including depressed mood and euphoric mood).
• Cataract.
• Hypertension.
• Peptic ulcer (with possible peptic ulcer perforation and peptic ulcer haemorrhage).
• Skin atrophy, acne.
• Muscular weakness, growth retardation.
• Impaired healing.
• Blood potassium decreased.

Immunosuppressant effects/ Increased susceptibility to infections

• Corticosteroids may increase susceptibility to infection, 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.
• Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals.
• 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.
• Exposure to measles should be avoided. Medical advice must be sought immediately if exposure occurs. Prophylaxis with normal intramuscular immunoglobulin may be needed.
• Similarly corticosteroids should be used with great care in patients with known or suspected parasitic infections such as Strongyloides (threadworm) infestation, which may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
• Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. The antibody response to other vaccines may be diminished.
• The use of corticosteroids 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.
• Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.
• The role of corticosteroids in septic shock has been controversial, with early studies reporting both beneficial and detrimental effects. More recently, supplemental corticosteroids have been suggested to be beneficial in patients with established septic shock who exhibit adrenal insufficiency. However, their routine use in septic shock is not recommended. A systematic review of short-course high-dose corticosteroids did not support their use. However, meta-analyses, and a review have suggested that longer courses (5 – 11 days) of low-dose corticosteroids might reduce mortality.

Immune system

• Because rare instances of skin reactions and anaphylactic/anaphylactoid reactions have occurred in patients receiving corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.

Endocrine effects

• In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated.
• 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. In addition, acute adrenal insufficiency leading to a fatal outcome may occur if glucocorticoids are withdrawn abruptly.
  + Patients receiving doses of systemic corticosteroid greater than 32 mg daily of methylprednisolone.
  + Patients repeatedly taking doses in the evening.
• A steroid “withdrawal syndrome,” seemingly unrelated to adrenocortical insufficiency, may also occur following abrupt discontinuance of glucocorticoids. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, weight loss, and/or hypotension. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels.
• Glucocorticoids can produce or aggravate Cushing’s syndrome, therefore glucocorticoids should be avoided in patients with Cushing’s disease.
• Particular care is required when considering the use of systemic corticosteroids in patients with hypothyroidism and frequent patient monitoring is necessary.

Metabolism and nutrition disorders

• Corticosteroids, including methylprednisolone, can increase blood glucose, worsen pre-existing diabetes, and predispose those on long-term corticosteroid therapy to diabetes mellitus. Particular care is required when considering the use of systemic corticosteroids in patients with diabetes mellitus (or a family history of diabetes) and frequent patient monitoring is necessary.

Psychiatric effects

• 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.

Nervous system effects

• Particular care is required when considering the use of systemic corticosteroids in patients with seizure disorders and myasthenia
• There have been reports of epidural lipomatosis in patients taking corticosteroids, typically with long-term use at high doses.

Ocular effects

• Visual disturbance may be reported with systemic and topical corticosteroid use.
• Particular care is required when considering the use of systemic corticosteroids in patients with glaucoma (or a family history of glaucoma) and ocular herpes simplex as there is a fear of corneal perforation.
• Prolonged use of corticosteroids may produce posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos or increased intraocular pressure, which may result in glaucoma with possible damage to the optic nerves.
• Secondary fungal and viral infections of the eye may also be enhanced in patients receiving glucocorticoids.

Cardiac events

• Adverse effects of glucocorticoids on the cardiovascular system, such as dyslipidemia and hypertension, may predispose treated patients with existing cardiovascular risk factors to additional cardiovascular effects, if high doses and prolonged courses are used.
• Systemic corticosteroids should be used with caution, and only if strictly necessary, in cases of congestive heart failure.
• Particular care is required when considering the use of systemic corticosteroids in patients with recent myocardial infarction (myocardial rupture has been reported).
• Care should be taken for patients receiving cardioactive drugs such as digoxin because of steroid induced electrolyte disturbance/potassium loss.

Vascular effects

• Particular care is required when considering the use of systemic corticosteroids in patients with hypertension, predisposition to thrombophlebitis.
• Thrombosis including venous thromboembolism has been reported to occur with corticosteroids. As a result corticosteroids should be used with caution in patients who have or may be predisposed to thromboembolic disorders.

Gastrointestinal effects

• High doses of corticosteroids may produce acute pancreatitis.
• Particular care is required when considering the use of systemic corticosteroids in patients with peptic ulceration, fresh intestinal anastomoses, abscess or other pyogenic infections, ulcerative colitis, diverticulitis. Glucocorticoid therapy may mask peritonitis or other signs or symptoms associated with gastrointestinal disorders such as perforation, obstruction or pancreatitis. In combination with NSAIDs, the risk of developing gastrointestinal ulcers is increased.

Hepatobiliary effects

• Particular care is required when considering the use of systemic corticosteroids in patients with liver failure or cirrhosis and frequent patient monitoring is necessary.
• Rarely hepatobiliary disorders were reported, in the majority of these cases, they were reversible after withdrawal of therapy. Therefore appropriate monitoring is required.

Musculoskeletal effects

• An acute myopathy has been reported 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 anticholinergics, such as neuromuscular blocking drugs (e.g. pancuronium).
• Particular care is required when considering the use of systemic corticosteroids in patients with osteoporosis (post-menopausal females are particularly at risk) and frequent patient monitoring is necessary.

Renal and urinary

• Caution is required in patients with systemic sclerosis because an increased incidence of scleroderma renal crisis has been observed with corticosteroids, including methylprednisolone. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.
• Particular care is required when considering the use of systemic corticosteroids in patients with renal insufficiency and frequent patient monitoring is necessary.

Injury, poisoning and procedural complications

• Systemic corticosteroids are not indicated for, and therefore should not be used to treat, traumatic brain injury. A multicenter study revealed an increased mortality at 2 weeks and 6 months after injury in patients administered methylprednisolone sodium succinate compared to placebo. A causal association with methylprednisolone sodium succinate treatment has not been established.

Others

• 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.
• 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.
• Aspirin and non-steroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids.
• Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
• Paediatric population: Corticosteroids cause growth retardation in infancy, childhood and adolescence. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. 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.
  Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure.
  High doses of corticosteroids may produce pancreatitis in children.
• 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.
• Stadsone 4 contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
• Stadsone 4 contains sucrose (saccharose). Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
• Stadsone 4 should be used during pregnancy and lactation only after a careful assessment of the benefit-risk ratio to the mother, embryo, foetus or child.
• Undesirable effects, such as dizziness, vertigo, visual disturbances and fatigue are possible after treatment with corticosteroids.