Each vial contains Hydrocortisone Sodium Succinate equivalent to Hydrocortisone 100 mg.
Pharmacology: Phamacodynamics: Mode or Mechanisms of Action: Hydrocortisone is the principal glucocorticosteroid synthesised by the adrenal cortex in man. Its mineralocorticoid action is weak (0.1% of aldosterone).
Corticosteroids: Diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA, and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for two categories of effects of systemic corticosteroids. However, these agents may suppress transcription of mRNA in some cells (e.g. lymphocytes).
Anti-inflammatory (steroidal): Glucocorticoids decrease or prevent tissue responses to inflammatory processes, thereby reducing development of symptoms of inflammation without affecting the underlying cause. Glucocorticoids inhibit accumulation of inflammatory cells, including macrophages and leukocytes, at sites of inflammation. They also inhibit phagocytosis, lysosomal enzyme release, and synthesis and/or release of several chemical mediators of inflammation. Immunosuppressant actions may also contribute significantly to the anti- inflammatory effect.
lmmunosuppressant: May involve prevention or suppression of cell-mediated (delayed hypersensitivity) immune reactions as well as more specific actions affecting the immune response. Glucocorticoids reduce the concentration of thymus-dependent lymphocytes (T-lymphocytes), monocytes, and eosinophils. They also decrease binding of immunoglobulin to cell surface receptors and inhibit the synthesis and/or release of interleukins, thereby decreasing T-lymphocyte blastogenesis and reducing expansion of the primary immune response. Glucocorticoids may also decrease passage of immune complexes through basement membranes and decrease concentrations of complement components and immunoglobulins.
Other actions/effects: Pharmacologic (supra-physiologic) doses of erogenous corticosteroids produce hypothalamic-pituitary-adrenal (HPA) axis suppression via a negative feedback mechanism, i.e., they inhibit pituitary ACTH secretion, thereby reducing ACTH-mediated production of corticosteroids and androgens in the adrenal cortex.
Glucorticoids also: Stimulate protein catabolism and induce enzymes responsible for metabolism of amino acids; Increase glucose availability by inducing hepatic enzymes involved in gluconeogenesis, stimulating protein catabolism and decreasing peripheral utilization of glucose; Increase lipolysis and mobilize fatty acids from adipose tissues, leading to increased plasma fatty acid concentrations; Decrease bone formation and increase bone resorption.
Pharmacokinetics: Absorption: Rapidly absorbed.
Time to peak concentration: About one hour.
Bio-transformation: Primarily hepatic (slow and rather limited); also renal and tissue; mostly to inactive metabolites.
Duration of action: Depends upon the solubility of the dosage form as well as the biological (tissue) half-life (about 190 minutes).
Protein binding: >90% bound to plasma proteins.
Elimination: Renal mainly as inactive metabolites.
Replacement therapy for adrenal-cortical failure or hypopituitarism.
In patients with known or suspected adrenal insufficiency, intravenous or intra-muscular administration of a rapidly acting corticosteroid (such as hydrocortisone) is indicated prior to surgery, including dental surgery, or if shock, severe trauma, illness, or other stress conditions occur. Patients already receiving replacement therapy require supplemental pharmacologic doses; Congenital adrenal hyperplasia; Status asthmaticus; Allergic and anaphylactic reactions; Ulcerative colitis; Soft tissue or joint inflammation; Collagen diseases; Dermatological diseases; Hypercalcaemia associated with cancer.
Usual adult and adolescent dose: Intra-muscular or intravenous, 100 to 500 mg (base); may be repeated every two to six hours, depending upon patient condition and response.
Note: Initial intravenous dosage should be administered over a period of thirty seconds (100-mg dose) to ten minutes (doses of 500 mg or higher).
Maintenance dosage (if required) should be no less than 25 mg per day.
Anaphylactic shock: May be a useful adjunct to adrenaline in severely affected patients; may be given intravenously in a dose equivalent to 100 to 300 mg of hydrocortisone.
Usual paediatric dose: Adreno-cortical insufficiency: Intra-muscular or intravenous, 186 to 280 mcg (0.186 to 0.28 mg) (base) per kg of body weight or 10 to 12 mg (base) per m2 of body surface a day in three divided doses.
Other indications: Intra-muscular, 666 mcg (0.666 mg) to 4 mg (base) per kg of body weight or 20 to 120 mg (base) per m2 of body surface every twelve to twenty-four hours.
There are no symptoms of an acute parenteral over-dosage known. The adverse effects of corticosteroids are nearly always due to their use in excess of normal physiological requirements. They should be treated symptomatically, where the dosage should be reduced or the drug slowly withdrawn.
Note: Reconstitution For IV or IM Injection, reconstitute the vial by aseptically adding not more than 2ml water for injection.
Treatment of adverse effects: For gastrointestinal effects: Administration of antacids between meals may relieve indigestion or mild gastrointestinal irritation that may occur during parenteral therapy. However, the efficacy of antacids or other anti-ulcer medications in preventing severe gastrointestinal problems, such as ulceration, haemorrhage, and/or bowel perforation, during corticosteroid therapy has not been established.
Mental depression or psychoses: If possible, decrease corticosteroid dosage or discontinue therapy. Phenothiazines may be administered if necessary. Lithium has been recommended. Some patients may require electro-convulsive therapy if severe depression persist. Tricyclic antidepressants should not be used since they do not relieve, and may exacerbate, corticosteroid-induced mental disturbances.
For withdrawal effects (non-HPA axis suppression): Administration of aspirin or another NSAID may alleviate some of the symptoms of this condition.
Unless considered life saving, systemic administration of corticosteroids is contraindicated in patients with peptic, gastric and duodenal ulcers, osteoporosis, psychoses, or severe psychoneuroses. Corticosteroids are contraindicated in patients with severe systemic or fungal infections and certain viral infections (e.g. varicella / chickenpox and herpes genitalis infections) in the absence of specific treatment. lntra-muscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura (ITP). lt is also contraindicated in patients with glaucoma and known hypersensitivity to components of this product.
Following intra-articular injection, the injected joints should not be overused even if pain is relieved, because of the increased risk of joint damage or deterioration. It is recommended that weight-bearing joints be rested for 24 to 48 hours post-injection.
Concurrent disease: Caution should be exercised in administering large doses of hydrocortisone to patients with known cardiac failure, hypertension, peptic ulceration, glaucoma, epilepsy, diabetes mellitus, chronic psychosis, and a past history of tuberculosis. The effects are enhanced in hepatic disease and hypothyroidism.
Adrenal Suppression: During prolonged therapy adrenal atrophy may develop and persist for years after stopping. Abrupt withdrawal after a prolonged period may lead to adrenal insufficiency, hypotension or death; however in most asthma patients (who continue to receive other appropriate treatment), abrupt withdrawal after courses of up to 3 weeks has not resulted in adverse effects. Withdrawal may also be associated with fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss.
Any significant intercurrent illness, trauma, or surgical procedure requires a temporary increase in dosage, or if already stopped, temporary re-introduction of corticosteroid.
Patients should carry a Steroid Treatment Card giving clear guidance on precautions to minimise risk and providing details or prescriber, drug, dosage and duration of treatment.
High Risk Groups: Fertility: Corticosteroids have been reported to increase or decrease the number or motility of spermatozoa but it is not known whether reproductive capacity in humans is adversely affected.
Use in Pregnancy: Corticosteroids cross the placenta. Although adequate studies have not been done in humans, there is some evidence that pharmacologic doses of corticosteroids may increase the risk of placental insufficiency, decreased birth weight, or stillbirth. However, teratogenic effects in humans have not been confirmed. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism and replacement therapy administered if required.
Use in Lactation: Problems in humans have not been documented. Breast-feeding is not recommended because it is excreted in breast milk and may cause unwanted effects, such as growth suppression and inhibition of endogenous steroid production, in the infant.
Use in Children: Chronic use of corticosteroids may suppress growth and development of the paediatric or adolescent and should be undertaken with caution. Also, paediatric patients may be at increased risk of developing osteoporosis, avascular necrosis of the femoral heads, glaucoma, or cataracts during prolonged therapy. Children and adolescents receiving prolonged therapy should be closely monitored. Large doses or corticosteroids may be associated with intra-cranial hypertension in children.
Use in Elderly: Geriatric patients may be more likely to develop hypertension during corticosteroid therapy. Geriatric patients, especially postmenopausal women, may also be more likely to develop glucocorticoid-induced osteoporosis.
Pregnancy: Corticosteroids cross the placenta. Although adequate studies have not been done in humans, there is some evidence that pharmacologic doses of corticosteroids may increase the risk of placental insufficiency, decreased birth weight, or stillbirth. However, teratogenic effects in humans have not been confirmed. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism and replacement therapy administered if required.
Breast-feeding: Problems in humans have not been documented. Breast-feeding is not recommended because it is excreted in breast milk and may cause unwanted effects, such as growth suppression and inhibition of endogenous steroid production, in the infant.
Fertility: Corticosteroids have been reported to increase or decrease the number or motility of spermatozoa but it is not known whether reproductive capacity in humans is adversely affected.
Adverse reactions, associated with prolonged systemic glucocorticoid therapy, are unlikely when high doses are administered over a short period of time. Nevertheless, gastric and duodenal ulceration, with possible perforation and haemorrhage, may occasionally occur.
The following adverse reactions have been associated with prolonged systemic glucocorticoid therapy.
Endocrine and Metabolic Disturbances:
Cushing-like syndrome, hirsutism, menstrual irregularities, premature epiphyseal closure, secondary adrenal-cortical and pituitary unresponsiveness, decreased glucose tolerance, negative nitrogen and calcium balance.
Fluid and Electrolyte Disturbances:
Sodium and fluid retention, hypertension, potassium loss, hypokalaemic alkalosis.
Myopathy, abdominal distension, osteoporosis, aseptic necrosis of femoral and humeral heads.
Gastric and duodenal ulceration, perforation and haemorrhage.
Impaired wound healing, skin atrophy, striae, petechiae and ecchymoses, bruising, facial erythema, increased sweating, acne.
Psychic disturbances ranging from euphoria to frank psychotic manifestations, convulsions; in children, pseudo-tumour cerebri (benign intra-cranial hypertension) with vomiting and papilloedema.
Glaucoma, increase in intra-ocular pressure, posterior sub-capsular cataracts.
Increased susceptibility to infections, decreased responsiveness to vaccination and skin tests. Hypersensitivity reactions may occasionally occur. Local adverse reactions include post-injection flare and a painless destruction of the joint reminiscent of Charcot's arthropathy, especially with repeated intra-articular injections.
Diuretics: Concurrent use of potassium-depleting diuretics with corticosteroids may result in severe hypokalaemia.
Digitalis glycosides: Concurrent use with glucocorticoids may increase the possibility of arrhythmias or digitalis toxicity associated with hypokalaemia.
Anti-diabetic agents, sulfonylurea or Insulin: Glucocorticoids may increase blood glucose concentration; dosage adjustment of one or both agents may be necessary during concurrent use.
Alcohol or Anti-inflammatory drugs, non-steroidal (NSAIDS): Risk of gastrointestinal ulceration or haemorrhage may be increased when these substances are used concurrently with glucocorticoids: however, concurrent use of NSAIDS in the treatment of arthritis may provide additive therapeutic benefit and permit glucocorticoid dosage reduction.
Anticoagulants, coumarin, or indandione - derivative, or Heparin or Streptokinase or Urokinase: Effects of coumarin or indandione derivatives are usually decreased but may be increased in some patients when used concurrently with glucocorticoids. Dosage adjustments based on prothrombin time determinations may be necessary during and after glucocorticoid therapy.
Vaccines, live virus or other immunizations: Administration may increase the risk of the patient's developing the viral disease and/or decrease the patient's antibody response to the vaccine and is not recommended.
Liver enzyme-inducing drugs, e.g. rifampicin, ephedrine, barbiturates, phenytoin, phenobarbitone and primidone: Concurrent use may decrease the corticosteroid effect because of increased corticosteroid metabolism resulting from induction of hepatic microsomal enzymes.
Salicylates: Glucocorticoids may increase salicylate excretion and reduce salicylate plasma concentrations so that the salicylate dosage requirement may be increased; salicylism may occur when glucocorticoid dosage is subsequently decreased or discontinued, especially in patients receiving large (anti-rheumatic) doses of salicylates; also, the risk of gastrointestinal ulceration or haemorrhage may be increased.
Combinations containing any of the following medications depending on the amount present, may also interact with this medications: Acetaminophen (paracetamol); Aminoglutethimide; Amphotericin B, parenteral or Carbonic anhydrase inhibitors; Anabolic steroids or Androgens; Anticholinergics, especially atropine and related compounds; Antidepressants, tricyclic; Contraceptives, oral, estrogen-containing, or Oestrogen; Folic Acid; Immunosuppressant agents, other; lsoniazid, Mexiletine; lophendylate or Metrizamide; Mitotane; Neuromuscular blocking agents, nondepolarizing; pancuronium; Potassium supplements; Ritodrine; Sodium-containing medication or foods; Somatrem or Somatropin; Streptozocin.
Reconstituted solution should be used only if it is clear and should be discarded after 1 day. After reconstitution, protect the solution from light and freezing.
Store below 30°C.
Shelf-Life: 2 years.
H02AB09 - hydrocortisone ; Belongs to the class of glucocorticoids. Used in systemic corticosteroid preparations.
Powd for inj 100 mg (white or almost white coloured in vial) x 2 mL x 25's.