Special Warning : אזהרת שימוש

Warnings
The lowest possible dose of corticosteroid should be used to control the condition being treated. When reduction in dosage is possible, it should be gradual.
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.


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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 .
In patients receiving corticosteroid therapy and subjected to unusual stress, such as trauma or surgery, increased dosage of corticosteroids before, during and after the stressful situation, is indicated.
Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug. Anaphylactoid and hypersensitivity reactions have been reported for dexamethasone sodium phosphate Injection (see Adverse Reactions).
After parenteral administration of glucocorticoids serious anaphylactoid reactions, such as glottis oedema, urticaria and bronchospasm, have occasionally occurred, particularly in patients with a history of allergy. If such an anaphylactoid reaction occurs, the following measures are recommended: immediate slow intravenous injection of 0.1 - 0.5 ml of adrenaline (solution of 1:1000: 0.1 - 0.5 mg adrenaline dependent on body weight), intravenous administration of aminophylline and artificial respiration if necessary.
Corticosteroids should not be used for the management of head injury or stroke because it is unlikely to be of any benefit and may even be harmful Dexacort Forte preparation contains a sulfite preservative which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown, but is probably low. Sulfite sensitivity is observed more frequently in asthmatic individuals.
Average and large doses of cortisone or hydrocortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium.
Dietary salt restriction and potassium supplementation may be necessary. Calcium levels should be monitored, since corticosteroids increase calcium excretion.
Prolonged use may produce posterior subcapsular cataracts and glaucoma with possible damage to the optic nerves. It may also enhance the establishment of secondary ocular infections due to fungi or viruses.
Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Moreover, corticosteroids may affect the nitroblue- tetrazolium test for bacterial infection and produce false negative results (see Diagnostic Interference). If an infection occurs during therapy, it should be promptly controlled by a suitable antimicrobial agent.
The use of systemic corticosteroids in active tuberculosis should be restricted to cases of fulminating or disseminated disease, where the corticosteroid is used for 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.
Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control drug reactions due to amphotericin B. Moreover, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone, was followed by cardiac enlargement and congestive failure.


DEXACORT Forte Injection       22- 1. 2013 RH                    Page 2 of 10 Administration of live virus vaccines, including smallpox, 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. However, immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison’s disease.
Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (Consult the respective prescribing information for VZIG and IG). If chicken pox develops, treatment with antiviral agents may be considered.
Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid- induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Corticosteroids may activate latent amebiasis. Therefore, it is recommended that amebiasis, whether latent or active, should be ruled out before therapy with a corticosteroid is instituted in patients prone to the disease, e.g. patients with unexplained diarrhea or patients who have spent time in endemic areas.
It has been reported that the use of corticosteroids in cerebral malaria is associated with a prolonged coma and an increased incidence of pneumonia and gastrointestinal bleeding.
Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients.

Use in Pregnancy
Since adequate human reproduction studies have not been performed with corticosteroids, the use of these drugs in pregnant women or women of childbearing potential requires that the expected benefits of the drug be weighed against the possible hazards to mother and fetus. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Use in Breastfeeding
Corticosteroids appear in breast milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other unwanted effects. Mothers taking pharmacological doses of corticosteroids should be advised not to breastfeed.

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.
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Adverse Reactions
Local adverse reactions include post-injection flare, and a painless destruction of the joint reminiscent of Charcots arthropathy especially with repeated intra-articular injection.
The incidence of predictable undesirable effects, including hypothalamic-pituitary- adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and the duration of treatment. Cases of ruptured tendon have been reported.
Local injection of glucocorticoid may produce systemic effects 
Fluid and Electrolyte Disturbances
Sodium retention, fluid retention, congestive heart failure in susceptible patients, potassium loss, hypokalemic alkalosis, hypertension.

Musculoskeletal
Muscle weakness, steroid myopathy, loss of muscle mass (muscular atrophy) , tendon rupture, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathological fractures of long bones, proximal myopathy .

Gastrointestinal
Peptic ulcer with possible subsequent perforation and hemorrhage, perforation of the intestine particularly in patients with inflammatory bowel disease, pancreatitis, candidiasis , abdominal distension, ulcerative esophagitis.

Dermatological
Impaired wound healing, thin fragile skin, petechiae and ecchymoses, erythema, increased sweating.
Corticosteroids may suppress reactions to skin tests.
Burning or tingling, especially in the perineal area (after I.V.injection).
Other cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic edema.

Neurological
A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported.
Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown Convulsions, increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment, vertigo, headache, psychic disturbances, euphoric side effects cerebral palsy in preterm infants.

Endocrine
Menstrual irregularities, amenorrhea, development of Cushingoid state, suppression of growth in children, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, increased requirements of insulin or oral hypoglycemic agents in diabetics, hirsutism.

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Opthalmological
Posterior subcapsular cataracts, increased intraocular pressure, glaucoma, exophthalmus, retinopathy of prematurity.

Metabolic
Negative nitrogen balance due to protein catabolism.

Blood/Vascular Disorders :
Thromboembolism, polymorphonuclear           leucocytosis,   neuropathy,     vasculitis, development of Diabetes Mellitus

Effect on Bones and Joints
Osteoporosis, arthropathy, osteonecrosis of femoral and/or humeral heads (aseptic or avascular necrosis).

Cardiovascular
Myocardial rupture following recent myocardial infarction.
Hypertrophic cardiomyopathy in low birth weight infants
Impaired cardiac contractility

Anti-inflammatory and Immunosuppressive effects
Increased susceptibility and severity of infections with suppression of clinical symptoms and signs. Diminished lymphoid tissue and immune response.
Opportunistic infections, recurrence of dormant tuberculosis and decreased responsiveness to vaccination and skin tests.

Other
Anaphylactoid or hypersensitivity reactions, thromboembolism, weight gain, increased appetite, nausea, malaise, hiccups.
The following additional adverse reactions are related to parenteral corticosteroid therapy: rare instances of blindness associated with intra-lesional therapy around the face and head, hyperpigmentation or hypopigmentation, subcutaneous and cutaneous atrophy, sterile abscess, post-injection flare (following intra-articular use) and Charcot-like arthropathy.

Withdrawal Symptoms
Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death.
A 'withdrawal syndrome' may also occur including, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.

Precautions
Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case, as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.
Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including fever, myalgia, arthralgia, and malaise. This may occur in patients even without evidence of adrenal insufficiency.


DEXACORT Forte Injection      22- 1. 2013 RH                    Page 5 of 10 Drug-induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by the gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy. Therefore, in any situation of stress occurring during this period, hormone therapy should be reinstituted. If the patient is receiving steroids already, the dosage may have to be increased. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.
Corticosteroids have an enhanced effect on patients with hypothyroidism and hepatic cirrhosis.
Corticosteroids should be used with caution in patients with ocular herpes simplex because of possible corneal perforation.
Psychic derangements may appear when corticosteroids are used. These can range from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. In addition, corticosteroids may aggravate existing emotional instability or psychotic tendencies.
Co-administration of thalidomide with dexamethasone phosphate injection should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use.
Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.
Corticosteroids should be used with caution in non-specific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic infection, diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis and myasthenia gravis. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving large doses of corticosteroids may be minimal or absent. Fat embolism has been reported as a possible complication of hypercortisonism.
Steroids may increase or decrease motility and number of spermatozoa in some patients.
Growth and development of infants and children receiving prolonged corticosteroid therapy should be carefully observed.
Routine laboratory studies, such as urinalysis, two-hour postprandial blood sugar, determination of blood pressure and body weight, and a chest X-ray, should be made at regular intervals during prolonged therapy. Upper GI X-rays are desirable in patients with an ulcer history or significant dyspepsia.

Special Precautions
(see also Contraindications)
Particular care is required when considering the use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.
 a. Osteoporosis (post-menopausal females are particularly at risk).
b. Hypertension or congestive heart failure.
c. Existing or previous history of severe affective disorders (especially previous steroid psychosis).
d. Diabetes mellitus (or a family history of diabetes).
e. History of tuberculosis, since glucocorticoids may induce reactivation.
f. Glaucoma (or a family history of glaucoma).
g. Previous corticosteroid-induced myopathy.
h. Liver failure.
i. Renal insufficiency.
j. Epilepsy.
k. Gastro-intestinal ulceration.
DEXACORT Forte Injection      22- 1. 2013 RH                   Page 6 of 10 l. Migraine m. Certain parasitic infestations in particular amoebiasis.
n. Incomplete statural growth since glucocorticoids on prolonged administration may accelerate epiphyseal closure o. Patients with Cushing's syndrome
In the treatment of conditions such as tendinitis or tenosynovitis care should be taken to inject into the space between the tendon sheath and the tendon as cases of ruptured tendon have been reported.

Effects on Driving