Dexoph Eye Drops

Each mL of solution contains dexamethasone sodium phosphate equivalent to 4 mg of dexamethasone phosphate.

Dexamethasone phosphate (as sodium) is a white or slightly yellow, very hygroscopic, crystalline powder. It is odourless or has a slight odour of alcohol.

Dexamethasone phosphate (as sodium) has a chemical formula of C₂₂H₂₈FNa₂O₈P and a molecular weight of 516.4.

Dexamethasone phosphate (as sodium) is soluble 1 in 2 of water, slightly soluble in alcohol, practically insoluble in chloroform and ether, and very slightly soluble in dioxan.

Excipients/Inactive Ingredients: Sodium citrate, disodium edetate and sodium sulfite anhydrous. No preservatives are present.

The pH of the solutions is adjusted using sodium hydroxide and/or hydrochloric acid.

Replacement Therapy- Adrenocortical Insufficiency: Dexamethasone has predominantly glucocorticoid activity and therefore is not a complete replacement therapy in cases of adrenocortical insufficiency. Dexamethasone should be supplemented with salt and/or a mineralocorticoid, such as deoxycorticosterone. When so supplemented, dexamethasone is indicated in: Acute Adrenocortical Insufficiency: Addison's disease, bilateral adrenalectomy.

Relative Adrenocortical Insufficiency: Prolonged administration of adrenocortical steroids can produce dormancy of the adrenal cortex. The reduced secretory capacity gives rise to a state of relative adrenocortical insufficiency which persists for a varying length of time after therapy is discontinued. Should a patient be subjected to sudden stress during this period of reduced secretion (for up to two years after therapy has ceased) the steroid output may not be adequate. Steroid therapy should therefore be reinstituted to help cope with stress such as that associated with surgery, trauma, burns, or severe infections where specific antibiotic therapy is available.

Primary and Secondary Adrenocortical Insufficiency.

Disease Therapy: Dexamethasone is indicated for therapy of the following diseases: Collagen Diseases: Systemic lupus erythematosus, polyarteritis nodosa, dermatomyositis, giant cell arteritis, adjunctive therapy for short term administration during an acute episode or exacerbation, acute rheumatic carditis - during an exacerbation or as maintenance therapy.

Pulmonary Disorders: Status asthmaticus, chronic asthma, sarcoidosis, respiratory insufficiency.

Blood Disorders: Leukaemia, idiopathic thrombocytopaenic purpura in adults, acquired (autoimmune) haemolytic anaemia.

Rheumatic Diseases: Rheumatoid arthritis, osteoarthritis, adjunctive therapy for short term administration during an acute episode or exacerbation of rheumatoid arthritis or osteoarthritis.

Skin Diseases: Psoriasis, erythema multiforme, pemphigus, neutrophilic dermatitis, localised neurodermatitis, exfoliative dermatitis, sarcoidosis of skin, severe seborrhoeic dermatitis, contact dermatitis.

Gastrointestinal Disorders: Ulcerative colitis, regional enteritis.

Oedema: Cerebral oedema associated with primary or metastatic brain tumours, neurosurgery or stroke, oedema associated with acute non-infectious laryngospasm (or laryngitis).

Eye Disorders: Allergic conjunctivitis, keratitis, allergic corneal marginal ulcers, chorioretinitis, optic neuritis, anterior ischaemic optic neuropathy.

Neoplastic States: Cerebral neoplasms, hypercalcaemia associated with cancer, leukaemias and lymphomas in adults, acute leukaemia in children.

Endocrine Disorders: Adrenal insufficiency.

Preoperative and Postoperative Support: Dexamethasone may be used in any surgical procedure when the adrenocortical reserve is doubtful.

This includes the treatment of shock due to excessive blood loss during surgery.

Shock: Dexamethasone may be used as an adjunct in the treatment of shock. Dexamethasone should not be used as a substitute for normal shock therapy.

Intravenous and

Intramuscular Administration:

Intravenous or intramuscular dosage usually ranges from 0.5 to 24 mg of dexamethasone phosphate daily. The duration of therapy is dependent on the clinical response of the patient and as soon as improvement is indicated, the dosage should be adjusted to the minimum required to maintain the desired clinical response. Withdrawal of the drug on completion of therapy should be gradual.

Parenteral dexamethasone is generally reserved for patients who are unable to take dexamethasone orally or for use in an emergency situation.

Shock (of haemorrhagic, traumatic or surgical origin): Usual Dose: 2 to 6 mg/kg body weight as a single intravenous injection. This may be repeated in 2 to 6 hours if shock persists. An alternative regimen of 20 mg by intravenous injection initially, followed by continuous intravenous infusion of 3 mg/kg body weight per 24 hours, has been suggested. If required for intravenous infusion, dexamethasone phosphate may be diluted with glucose or sodium chloride injection.

High dose therapy should be continued only until the patient's condition has stabilised and usually for no longer than 48 to 72 hours.

To avoid microbial contamination hazards, infusion should be commenced as soon as practicable after preparation of the mixture and if storage is necessary, store solution at 2 to 8°C. Infusion should be completed within 24 hours of preparation of the solution and any residue discarded.

Warning: Further diluted solutions which are not clear, or which show evidence of particulate matter contamination, should be discarded.

Cerebral Oedema: The treatment schedule and route of administration should reflect the severity and aetiology of the cerebral oedema. Treatment needs to be tailored to the individual response. An initial dose of 10 mg intravenously followed by 4 mg intramuscularly every 6 hours until the symptoms of oedema subside (usually after 12 to 24 hours). After 2 to 4 days the dosage should be reduced and gradually stopped over a period of 5 to 7 days. Patients with cerebral malignancy may require maintenance therapy with doses of 2 mg intramuscularly or intravenously 2 to 3 times daily.

High doses of dexamethasone may be used to initiate short term intensive therapy for acute cerebral oedema. Following an initial high loading dose, the dose is scaled down over the 7 to 10 day period of intensive therapy, and subsequently reduced to zero over the next 7 to 10 days.

Note: The intravenous and intramuscular route of administration of Dexoph Eye Drops Injection should only be used where acute illness or life threatening situations exist.

Oral therapy should be substituted as soon as possible.

Intra-Synovial & Soft Tissue Injections: Dosage varies with the degree of inflammation and the size and location of the affected area. Injections may be repeated from once every 3 to 5 days (e.g. for bursae) to once every 2 to 4 weeks (for joints). Frequent intra-articular injection may result in damage to joint tissues.

Administration: Dexoph Eye Drops may be administered intravenously or intramuscularly for systemic effect or as an intra-synovial or soft tissue injection for local effect.

Dosage of dexamethasone sodium phosphate is usually expressed in terms of dexamethasone phosphate.

Contains no antimicrobial agent. For single patient use. Use once only and discard any residue.

Administration of dexamethasone is contraindicated in the following cases: Hypersensitivity to dexamethasone or other corticosteroids or to any component of the injection; systemic fungal infections, or other systemic infections unless specific anti-infective therapy is given; administration of live virus vaccines; patients with myasthenia gravis, peptic ulcer, osteoporosis or psychoses; patients with a known hypersensitivity to sulfites.

Medicines that induce hepatic enzyme cytochrome P-450 isozyme 3A4 such as barbiturates, phenylbutazone, phenytoin or rifampicin, rifabutin, carbamazepine, primidone and aminoglutethimide may increase the metabolism and thus reduce the effects of corticosteroids. Ephedrine and aminoglutethimide may also increase dexamethasone metabolism.

Medicines that inhibit hepatic enzyme cytochrome P-450 isozyme 3A4 such as ketoconazole, ciclosporin or ritonavir may decrease glucocortiocoid clearance. A reduction in coritcosteroid dose may be needed to reduce the risk of adverse effects.

Antithyroid agents, oestrogens and other oral contraceptives may decrease hepatic metabolism and thus increase the effects of corticosteroids. The dose of corticosteroid may need to be adjusted if oestrogen therapy is commenced or stopped.

The effects of anticoagulant agents are usually decreased (but may be increased in some patients) if corticosteroids are administered concurrently. Close monitoring of the INR or prothrombin time is recommended.

Seizures have reportedly occurred in adult and paediatric patients receiving high dose corticosteroid therapy concurrently with cyclosporin.

Concurrent administration of dexamethasone with anticoagulants, heparin, streptokinase, urokinase, alcohol or non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin may increase the risk of gastrointestinal ulceration or haemorrhage. Aspirin should be used cautiously in conjunction with conticosteroids in patients with hypothrombinaemia. The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication. Patients should be observed closely for adverse effects of either medicine.

Potassium loss may occur as a result of dexamethasone administration. Concurrent administration of corticosteroids with potassium depleting diuretics (such as thiazides, frusemide or ethacrynic acid), carbonic anhydrase inhibitors such as acetazolamide or amphotericin B may result in severe hypokalaemia. The activity of digitalis glycosides and nondepolarising neuromuscular blocking agents may be potentiated as a result of glucocorticoid induced hypokalemia. The efficacy of potassium supplements and potassium sparing diuretics on serum potassium concentrations may be reduced by concurrent corticosteroid administration. Monitoring of serum potassium concentration is therefore recommended.

Glucocorticoids may increase blood glucose concentrations. Dosage adjustment of asparaginase and of anti-diabetic agents such as sulphonylureas and insulins may be necessary.

The growth promoting effect of somatropin may be inhibited. There is an increased risk of hypokalaemia if high doses of corticosteroids are given with high doses of salbutamol, salmeterol, terbutaline or formoteral. Concurrent use of antacids may decrease absorption of corticosteroids- efficacy may be decreased sufficiently to require dosage adjustments in patients receiving small doses of corticosteroids.

The following adverse effects have been reported with dexamethasone therapy. Except for allergic reactions, the adverse effects listed have been associated with prolonged therapy and/or high doses.

Endocrine Effects: Adrenal suppression, menstrual irregularities, amenorrhoea, development of Cushingoid state, weight gain, secondary adrenocortical and pituitary unresponsiveness particularly in times of stress (e.g. trauma, surgery or illness), decreased carbohydrate tolerance, increased requirements for insulin or oral hypoglycaemic agents in diabetes, development of diabetes mellitus, hyperglycaemia, hirsutism, growth suppression in infancy, childhood and adolescence, increased appetite.

Cardiovascular Effects: Thromboembolism, hypertension, polymorphonuclear leucocytosis, neuropathy, vasculitis, impaired myocardial contractility (prolonged treatment), congestive heart failure in susceptible patients, myocardial rupture following recent cardiac infarction, hypertrophic cardiomyopathy in low birth weight infants.

Musculoskeletal Effects: Proximal myopathy, osteoporosis, arthropathy, muscular atrophy, muscle weakness, steroid myopathy, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathological fracture of long bones, avascular osteonecrosis, tendon rupture, myalgia. These may occur as a result of protein catabolism associated with prolonged glucocorticoid therapy.

Ocular Effects: Increased intraocular pressure, glaucoma, papilloedema, posterior subcapsular cataracts, cataracts, exophthalmos, corneal or scleral thinning, retinopathy of prematurity, enhanced establishment of secondary fungal and viral eye infections.

Dermatological Effects: Impaired wound healing, hirsutism, skin atrophy, allergic dermatitis, urticaria, erythema, thin fragile skin, telangiectasia, petechiae and ecchymoses, increased sweating, may suppress skin test reactions, burning or tingling especially in the perineal area (after intravenous injection), angioneurotic oedema, acne, striae, easy bruising.

Anti-Inflammatory and Immunosuppressive Effects: Increased susceptibility to and severity of infections with suppression of clinical symptoms and signs. Opportunistic infections, recurrence of dormant tuberculosis.

Gastrointestinal Effects: Dyspepsia, nausea, peptic ulcer with possible perforation and haemorrhage, abdominal distension, abdominal pain, increased appetite which may result in weight gain, diarrhoea, acute pancreatitis, perforation of the small or large bowel particularly in patients with inflammatory bowel disease, abdominal distension, ulcerative oesophagitis, oesophageal candidiasis, nausea.

Neurological Effects: Euphoric side effects, mental disturbances, psychological dependence, depression, insomnia, dizziness, headache, convulsions, increased intracranial pressure with papilloedema, vertigo. Aggravation of schizophrenia, aggravation of epilepsy suicidal ideation, mania, delusions, hallucinations, irritability anxiety, insomnia and cognitive dysfunction.

Fluid and Electrolyte Disturbances: Electrolyte imbalance (retention of sodium and water with oedema and hypertension), potassium loss, hypokalaemic alkalosis, hypocalcaemia.

Metabolic Effects: Nitrogen depletion, negative nitrogen and calcium balance due to protein catabolism.

Other Effects: Allergic reactions, leucocytosis, anaphylactic or hypersensitivity reactions, weight gain, increased appetite, fatigue, malaise, hiccups.

Glucocorticoids, especially in large doses, increase susceptibility to infection, and may mask the symptoms of infection.

Too rapid a reduction of corticosteroids following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death. A steroid withdrawal syndrome, seemingly unrelated to adrenocortical insufficiency, and consisting of anorexia, nausea and vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, weight loss and/or hypotension, has been reported following abrupt withdrawal of glucocorticoids.

Hyperpigmentation or hypopigmentation, subcutaneous and cutaneous atrophy, sterile abscess, post-injection flare (following intra-articular use) and Charcot-like arthropathy have also been associated with parenteral corticosteroid therapy.