APR DAXOMET 30ml

S-16:

INFORMATION FOR THE USER

Dexamethasone Injection

Read all of this information carefully before you start taking this medicine because it contains important information for you.
• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

1. COMPOSITION:
Eachvial contains:
Dexamethasone phosphate – 4mg
Methyl paraben – 01.15% w/v
Propyl paraben – 0.02% w/v

For IV/IM use only.

2. DESCRIPTION:
Dexamethasone is a corticosteroid used for treatment of endocrine/non endocrine disorders responsive to corticosteroid therapy.

3. PHARMACOLOGICAL ACTION:
Dexamethasone possesses the actions& effects of other basic glucocorticoids & is among the most active members of its class.Glucocorticoids are adrenocortical steroids, both naturally occurring & synthetic, which are readily absorbed from the GI tract. They cause profound & varied metabolic effects & in addition, they modify the body’s immune responses to diverse stimuli. Naturally-occurring glucocorticoids (hydrocortisone & cortisone) which also have salt-retaining properties are used primarily for their potent anti-inflammatory effects in disorders of many organ systems.Dexamethasone has predominant glucocorticoid activity with little propensity to promote renal retention of sodium & water. Therefore it does not offer complete replacement therapy & must be supplemented with salt or desoxycorticosterone.
4. CLINICAL PHARMACOKINETICS:
The biological half-life in plasma is ~190 min.Binding to plasma proteins is less than for most other corticosteroids & is estimated to be ~77%.Up to 65% of a dose is excreted in the urine in 24 hrs, the rate of excretion being increased following concomitant administration of phenytoin.The more potent halogenated corticosteroids such as dexamethasone, appear to cross the placental barrier with minimal inactivation.
5. INDICATIONS:
Dexamethasone injection is indicated for the treatment of:
– Primary/secondary adrenocortical insufficiency
– Allergy/anaphylaxis
– Crohn’s disease
– Ulcerative colitis
– Raised intra cranial pressure secondary to cerebral tumours and infantile spasms
– Bronchial asthma
– Aspiration pneumonitis
– Toxic epidermal necrolysis
– Shock
– Miliary TB (With appropriate chemotherapy)
– Endotoxic shock (With appropriate chemotherapy)

6. CONTRAINDICATIONS:
– Systemic fungal infection
– Systemic infection unless specific anti-infective therapy is employed
– Hypersensitivity to the active ingredient or any other component of this medication
– Administration of live virus vaccines

7. WARNINGS AND PRECAUTIONS:
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.
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 the 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.
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.
Frequent intraarticular injections over a prolonged period may lead to joint destruction with bone necrosis. Intraarticular injection of corticosteroid may produce systemic adverse reactions including adrenal suppression.
Undesirable effects may be minimised by using the lowest effective dose for minimum period.
Corticosteroids may exacerbate systemic fungal infections & should not be used in the presence of such infections, unless they are needed to control drug reactions due to amphotericin.
Average & large doses of hydrocortisone/cortisone can cause elevation of BP, retention of salt & water & increased excretion of potassium.
The slower rate of absorption by IM administration should be recognised.
In patients on corticosteroid therapy subjected to unusual stress (e.g. intercurrent illness, trauma or surgical procedures), dosage should be increased before, during & after the stressful situation. Drug-induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids & may be minimised by gradual dosage reduction, being tapered off over weeks & months, depending on the dose and duration of treatment, but may persist for up to a year after discontinuation of therapy.
Stopping corticosteroids after prolonged therapy may cause withdrawal symptoms, including fever, myalgia, arthralgia & malaise.
In patients who have received more than physiological doses of systemic corticosteroids 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.
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 6mg daily 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 particularly if taken for greater than 3 weeks,
• when a short course has been prescribed within 1 year of cessation of long-term therapy (months/years),
• patients with reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy,
• patients receiving doses of systemic corticosteroid greater than 6mg daily
• patients repeatedly taking doses in the evening.
Because anaphylactoid reactions have occurred, rarely, in patients receiving parenteral corticosteroid therapy, appropriate precautions should be taken prior to administration, especially when the patient has a history of allergy to any drug.
Administration of live virus vaccines is contraindicated in individuals receiving immunosuppressive doses of corticosteroids. If inactivated viral or bacterial vaccines are administered to individuals receiving immunosuppressive doses of corticosteroids, the expected serum antibody response may not be obtained.
An apparent association between use of corticosteroids & left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients.
The use in active tuberculosis should be restricted to those cases of fulminating/disseminated TB in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculosis regimen.
May mask some signs of infection & new infections may appear during their use. Suppression of the inflammatory response & immune function increasing the susceptibility to infections & their severity. The clinical presentation may often be atypical & serious infections such as septicaemia & tuberculosis may be masked & reach an advanced stage before being recognised.
The use of corticosteroids in cerebral malaria is associated with a prolonged coma& an increased incidence of pneumonia & gastro-intestinal bleeding.
8. ADVERSE EFFECTS:
Fluid and electrolyte disturbances: Sodium retention, fluid retention, congestive heart failure, potassium loss, hypokalaemic alkalosis, hypertension, increased calcium excretion
Musculoskeletal: Muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral & humeral heads, pathological fracture of long bones, tendon rupture & post-injection flare
Gastrointestinal: Peptic ulcer with possible perforation & haemorrhage, perforation of the small & large bowel, pancreatitis, abdominal distension, ulcerative oesophagitis, dyspepsia, oesophageal candidiasis
Dermatological: Impaired wound healing, thin fragile skin, petechiae & ecchymoses, erythema, striae, telangiectasia, acne, increased sweating, possible suppression of skin tests, burning or tingling especially in the perineal area, other cutaneous reactions such as allergic dermatitis, urticaria, angioneurotic oedema & hypo- or hyper-pigmentation
Neurological: Convulsions, increased intracranial pressure with papilloedema, vertigo, headache, cerebral palsy in pre-term infants
Psychiatric: Affective disorders (such as irritable, euphoric, depressed & labile mood, & suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations & aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances & cognitive dysfunction including confusion & amnesia have been reported.
Endocrine: Menstrual irregularities, amenorrhoea, development of Cushingoid state, suppression of growth in children & adolescents, secondary adrenocortical & pituitary unresponsiveness, decreased carbohydrate tolerance, manifestation of latent diabetes mellitus, increased requirements for insulin or oral hypoglycaemic agents in diabetes, hirsutism
Anti-inflammatory & immunosuppressive effects: Increased susceptibility & severity of infections with suppression of clinical symptoms & signs; opportunistic infections, recurrence of dormant tuberculosis
Ophthalmic: Posterior subcapsular cataracts, increased intraocular pressure, papilloedema, corneal/scleral thinning, exacerbation of ophthalmic viral disease, glaucoma exophthalmos, rare instances of blindness associated with intralesional therapy around the face & head, retinopathy of prematurity, chorioretinopathy.
Metabolic: Negative nitrogen balance due to protein catabolism, negative calcium balance
Cardiovascular: Myocardial rupture following recent infarction, hypertrophic cardio-myopathy in low birth weight infants
Other: Hypersensitivity, including anaphylaxis has been reported, leucocytosis, thrombo-embolism, weight gain, increased appetite, nausea, malaise, hiccups & sterile abscess.
Multiple myeloma patients treated with lenalidomide or thalidomide in combination with dexamethasone have an increased risk of thromboembolic events including DVT & pulmonary embolism.
Withdrawal symptoms & signs: Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension & death. In some instances, withdrawal symptoms may simulate a clinical relapse of the disease for which the patient has been undergoing treatment.

9. DRUG INTERACTIONS:
Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinaemia.
The renal clearance of salicylates is increased by corticosteroids & salicylate dosage should be reduced along with steroid withdrawal.
As phenytoin, barbiturates, ephedrine, rifabutin, carbamazepine, rifampicin may enhance the metabolic clearance of corticosteroids, resulting in decreased blood levels & reduced physiological activity, the dosage may have to be adjusted.
False-negative results in the dexamethasone suppression test in patients being treated with indometacin have been reported.
Eefficacy of coumarin anticoagulants may be changed by concurrent corticosteroid treatment.
The desired effects of hypoglycaemic agents (including insulin) are antagonised by corticosteroids.
When concomitantly with potassium-depleting diuretics, patients should be observed closely for development of hypokalaemia.
May affect the nitroblue tetrazolium test for bacterial infection & produce false-negative results.
Antiretroviral protease inhibitors (ritonavir, darunavir, indinavir, lopinavir) are metabolised by CYP3A. May increase the clearance of medicines metabolised by CYP3A, resulting in lowered plasma conc.
Certain antiretroviral protease inhibitors (ritonavir, indinavir) may also be inhibitors of CYP3A themselves & as a result may increase the plasma conc.

10. DOSAGE:The recommended dose is 0.5-9mg per day depending on disease severity.

11. ADMINISTRATION:
For IV/IM use only.
Administration to be done by a registered medical practitioner/nurse in a proper sterile & hospital setting only.
12. STORAGE:
Do not store above 25°C. Store in the original package. Keep away from children. Do not expose to direct sunlight.

13. MANUFACTURED BY:

14. MARKETED BY:

Last revised on August 2020.