DEXAMED Tablet Ref.[28236] Active ingredients: Dexamethasone

Undesirable effects can be minimised by use of the lowest effective dose for minimum period, and when appropriate by administration of daily dose as a single morning dose, or, if possible, as a morning dose on alternate days. It is necessary to frequently review patients to titrate the dose against disease activity. When reduction in dosage is possible the reduction should be gradual.

Corticosteroids may exacerbate systemic fungal infections and should not be used in the presence of such infections unless they are needed to control life-threatening drug reactions due to amphotericin. Moreover, there have been cases reported in which concomitant use of amphotericin and hydrocortisone was followed by cardiac enlargement and heart failure.

Reports in the literature suggest an apparent association between use of corticosteroids and left-ventricular free-wall rupture after a recent myocardial infarction; therefore, corticosteroids should be used with great caution in these patients.

A report shows that the use of corticosteroids in cerebral malaria is associated with a prolonged coma and an increased incidence of pneumonia and gastro- intestinal bleeding.

Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, retention of salt and water and increased incidence of pneumonia and gastro-intestinal bleeding.

Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, retention of salt and water and increased excretion of potassium, but these effects are less likely to occur with synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

In patients on corticosteroid therapy subjected to unusual stress (e.g. intercurrent illness, trauma, or surgical procedure), dosage should be increased before, during and after the stressful situation.

In post marketing experience tumour lysis syndrome (TLS) has been reported in patients with haematological malignancies following the use of dexamethasone alone or in combination with other chemotherapeutic agents. Patient at high risk of TLS, such as patients with high proliferative rate, high tumour burden, and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precaution taken.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with 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.

Excipients

Dexamed tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not use this medicinal product.

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.

The metabolism of corticosteroids is enhanced by aminoglutethimide, carbamazepine, ephedrine, phenobarbitone, phenylbutazone, phenytoin, primidone, rifabutin and rifampicin, thus its therapeutic effect may be reduced.

Corticosteroids antagonise the desired effects of anti-hypertensives, diuretics and hypoglycaemic agents (including insulin).

The hypokalaemic effects of acetazolamide, carbenoxolone, loop diuretics and thiazide diuretics are enhanced by corticosteroids. Patients receiving corticosteroids and potassium depleting diuretics and/or cardiac glycosides, should be monitored for hypokalaemia. This is of particular importance in patients receiving cardiac glycosides since hypokalaemia increases the toxicity of these drugs. The effects of anti-hypertensive drugs are also antagonized by corticosteroids.

Concurrent corticosteroid therapy may enhance the efficacy of coumarin anticoagulants, close monitoring of INR or prothrombin time is necessary to avoid spontaneous bleeding.

Corticosteroids increase salicylate renal clearance, salicylate intoxication may result from steroid withdrawal.

Close monitoring of patients on non steroidal anti-inflammatory drugs is advised as the incidence and/or severity of gastro-intestinal ulceration may increase.

Pregnancy

In animals there is evidence of harmful effects in pregnancy, intra-uterine growth retardation, small increased risk of cleft palate and affects on brain growth and development have been reported. In the neonate, hypoadrenalism may occur.

Dexamethasone readily crosses the placenta. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man. However when administered for prolonged periods or repeatedly during pregnancy corticosteroids may increase the risk of intra-uterine growth retardation. Hypoadrenalism may in theory occur in the neonate following prenatal exposure to the corticosteroids but usually resolves spontaneously following birth and is rarely clinically important. As with all drugs corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks.

If corticosteroids are essential, patients with normal pregnancies may be treated as normal. Close monitoring is needed for pregnancies with pre-eclampsia or fluid retention. There is evidence of harmful effects on pregnancy in animals. Infants born to mothers who have received substantial doses of corticosteroids during the pregnancy should be carefully observed for signs of adrenal insufficiency.

Breast-feeding

Small amounts of corticosteroids are excreted in breast milk, although no data are available for dexamethasone. Infants of breast feeding mothers on pharmacological doses of corticosteroids must be monitored carefully for adrenal suppression symptoms. Mothers on high dose glucocorticoids should not breast feed.

Not relevant.

The following adverse effects with dexamethasone are listed below by system organ class; the frequency is not known (cannot be estimated from available data).

The frequency of predictable undesirable effects, including suppression of hypothalamic-pituitary-adrenal system, correlates with dosage, drug potency, timing of dose and treatment duration (see also section 4.4).

With the injection only, local adverse reactions include post injection flare, painless destruction of the joint (similar to Charcots arthropathy) especially with repeated intra-articular administration. Local injections may produce systemic effects.

Blood and lymphatic system disorders: leucocytosis.

Immune system disorders: Severity and susceptibility to infection increased with suppression of clinical symptoms, recurrence of dormant tuberculosis and opportunistic infections. Decrease in response to vaccination and skin tests (see also section 4.4).

Endocrine disorders: hypothalamic-pituitary-adrenal axis suppression, suppression of growth (infancy/childhood/adolescence), irregular menstruation and amenorrhoea. Cushinoid faces, hirsutism, premature epiphyseal closure, weight gain, carbohydrate tolerance impairment and increased anti-diabetic therapy requirement (impaired glucose tolerance and hyperglycaemia). Increased appetite. Negative calcium and protein balance. Secondary adrenocortical unresponsiveness, particularly in times of stress as in surgery or trauma.

Psychiatric disorders: aggravation of schizophrenia, depression, insomnia and psychological dependence., psychiatric disturbance, which can range from euphoria to frank psychotic manifestations, mental disturbances.

Nervous system disorders: headache, convulsions, vertigo. In children, usually after treatment withdrawal, increased intra-cranial pressure with papilloedema (pseudotumour cerebri). Epilepsy aggravation.

Eye disorders: intra-ocular pressure elevation, glaucoma, papilloedema, corneal or scleral thinning, posterior subcapsular cataracts, occasionally damage to the optic nerve, worsening of opthalmic viral or fungal infection. Chorioretinopathy. Vision, blurred (see also section 4.4).

Vascular disorders: hypertension, thromboembolism.

Gastrointestinal disorders: dyspepsia, peptic ulceration (with perforation and haemorrhage), acute pancreatitis, candidiasis, abdominal distension and vomiting.

Skin and subcutaneous tissue disorders: acne, bruising, impaired healing, skin atrophy, striae, telangiectasia. Petechiae and ecchymoses, erythema, increased sweating, burning or tingling, allergic dermatitis, candidiasis, urticaria, possible suppression of skin tests.

Musculoskeletal and connecting tissue disorders: osteoporosis, fractures of long bones and vertebra, avascular osteonecrosis, tendon rupture and proximal myopathy. Muscle weakness, proximal myopathy, premature epiphyseal closure, muscular atrophy.

General disorders and administration site conditions: Bronchospasm. Blindness associated with intralesional therapy around the face and neck, hyperpigmentation, hypopigmentation, subcutaneous and cutaneous atrophy, sterile abscess, post injection flare (following intra-articular injection): Charcot-like arthropathy.

Investigations: sodium and water retention with oedema, nitrogen depletion, hypokalaemic alkalosis, potassium and calcium loss.

Withdrawal symptoms/signs: following prolonged treatment, too rapid dosage reduction of corticosteroid can cause acute adrenal insufficiency, hypotension and death. A withdrawal syndrome may occur, including arthralgia, conjunctivitis, fever, myalgia, painful and itchy skin nodules, rhinitis and weight loss.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

None known.