Ivcort

Hydrocortisone sodium succinate.

Each vial contains: Hydrocortisone Sodium Succinate, USP equivalent to Hydrocortisone 100 mg.

Pharmacology: Pharmacodynamics: Hydrocortisone sodium succinate has the same metabolic and anti-inflammatory actions as Hydrocortisone. It is a glucocorticosteroid. Used in pharmacological doses, its actions suppress the clinical manifestations of disease in a wide range of disorders.
Pharmacokinetics: Hydrocortisone is readily absorbed from the gastrointestinal tract and peak blood concentrations are attained in about an hour. The biological half-life is about 100 minutes. It is more than 90% bound to plasma proteins. Following intramuscular injection, the absorption of the water-soluble sodium phosphate and sodium succinate esters is rapid, while absorption of Hydrocortisone free alcohol and its lipid-soluble esters is slower. Absorption of Hydrocortisone acetate after intra-articular or soft-tissue injection is also slow. Hydrocortisone is absorbed through the skin, particularly in denuded areas. Hydrocortisone is metabolised in the liver and most body tissues to hydrogenated and degraded forms such as tetrahydrocortisone and tetrahydrocortisol. These are excreted in the urine, mainly conjugated as glucuronides, together with a very small proportion of unchanged hydrocortisone. Hydrocortisone readily crosses the placenta.

Used in adrenocortical insufficiency, shock, hypersensitivity reactions like anaphylactic shock and angioedema, inflammatory bowel disease, hemorrhoids, rheumatic disease, ophthalmic and other conditions requiring immediate metabolic and anti-inflammatory actions of Hydrocortisone.

Hydrocortisone may be given intravenously, by slow injection or infusion, in the form of water-soluble derivatives such as Hydrocortisone sodium succinate or Hydrocortisone sodium phosphate when a rapid effect is required in emergencies: such conditions are acute adrenocortical insufficiency caused by Addisonian post-adrenalectomy crises, by the abrupt accident withdrawal therapy in corticosteroid treated patients, or by the inability of the adrenal glands to cope with increased stress in such patients certain allergic emergencies such as anaphylaxis; acute severe asthma and shock.
The usual dose is the equivalent of 100 to 500 mg of Hydrocortisone, repeated 3 or 4 times in 24 hrs, according to the severity of the condition and the patients response.
Children: Up to 1 year of age may be given 25 mg, those aged 1 to 5 years 50 mg, and those aged 6-12 years 100 mg. For local administration by injection into soft tissues Hydrocortisone in the form of the sodium phosphate or sodium succinate esters is usually employed; doses in terms of Hydrocortisone are usually 100 mg to 200 mg. For intra-articular injection Hydrocortisone acetate is usually used in doses of 5 to 50 mg depending upon the size of the joint. Or as prescribed by the physician.

There is no clinical syndrome of acute overdosage with corticosteroids. Hydrocortisone is dialysable. In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic.

Hydrocortisone sodium succinate for injection is contraindicated where there is known hypersensitivity to components and in systemic fungal infection unless specific anti-infective therapy is employed.

Adrenal cortical atrophy develops during prolonged therapy and may persist for months after stopping treatment. In patients who have received more than physiological doses of systemic corticosteroids (approximately 30 mg Hydrocortisone) for greater than 3 weeks, withdrawal should not be abrupt. Clinical assessment of disease activity may be needed during withdrawal.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it considered that the disease is unlikely to relapse. Abrupt withdrawal of doses up to 160 mg Hydrocortisone 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 systemic corticosteroids, particularly if taken for greater than 3 weeks; When a short course has been prescribed within one year of cessation of long-term therapy (months or years); Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy; Patients receiving doses of systemic corticosteroid greater than 160 mg Hydrocortisone; Patients repeatedly taking doses in the evening.
Immunosuppressant Effects/Increased Susceptibility to Infections: Corticosteroids may increase susceptibility to infection, may mask some signs of infection, and new infections may appear during their use. Suppression of the inflammatory response and immune function increases the susceptibility to fungal, viral and bacterial infections and their severity.
Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished.
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. Passive immunization with varicella/zoster immunoglobin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.
Exposure to measles should be avoided. Medical advice should be sought immediately if exposure occurs. Prophylaxis with normal intramuscular immunoglobulin may be needed.
The use of Hydrocortisone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with appropriate antituberculosis regimen.
Allergic reactions may occur. Rarely skin reactions and anaphylactic/anaphylactoid reactions have been reported following parenteral Hydrocortisone therapy. Care should be taken for patients receiving cardioactive drugs such as digoxin because of steroid induced electrolyte disturbance/potassium loss.
Ocular Effects: Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation. Establishment of secondary fungal and viral infections of the eye may also be enhanced in patients receiving glucocorticoids. Visual disturbance may be reported with systemic and topical corticosteroid use.
Thrombosis including venous thromboembolism has been reported to occur with corticosteroids. As a result, corticosteroids should be used with caution in patients who have or may be predisposed to thromboembolic disorders.
Endocrine Effects: In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during and after the stressful situation is indicated. A steroid "withdrawal syndrome", seemingly unrelated to adrenocortical insufficiency, may also occur following abrupt discontinuance of glucocorticoids. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, weight loss, and/or hypotension. There is an enhanced effect of corticosteroids on patients with hypothyroidism.
Cardiac Effects: Adverse effects of glucocorticoids on the cardiovascular system, such as dyslipidemia and hypertension, may predispose treated patients with existing cardiovascular risk factors to additional cardiovascular effects, if high doses and prolonged courses are used.
Systemic corticosteroids should be used with caution, and only if strictly necessary, in cases of congestive heart failure.
Special Precautions: Particular care is required when considering the use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.
Corticosteroids should be used with caution in patients with osteoporosis (post-menopausal females are particularly at risk); Hypertension; Existing or previous history of severe affective disorders (especially previous steroid psychosis); Corticosteroids, including Hydrocortisone, can increase blood glucose, worsen pre-existing diabetes, and predispose those on longterm corticosteroid therapy to diabetes mellitus; History of tuberculosis; Glaucoma (or a family history of glaucoma); Previous corticosteroid-induced myopathy; Liver failure or cirrhosis; Corticosteroids should be used with caution in patients with renal insufficiency; Epilepsy; Peptic ulceration; Fresh intestinal anastomoses; Predisposition to thrombophlebitis; Abscess or other pyogenic infections; Ulcerative colitis; Diverticulitis; Myasthenia gravis; Recent myocardial infarction (myocardial rupture has been reported); Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission; Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
Investigations: Hydrocortisone can cause elevation of blood pressure, salt and water retention and increased excretion of potassium. All corticosteroids increase calcium excretion.
Psychiatric effects: Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids. 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.
Gastrointestinal effect: High doses of corticosteroids may produce acute pancreatitis. In combination with nonsteroidal anti-inflammatory drugs (NSAIDs), the risk of developing gastrointestinal ulcers is increased.
Other: Aspirin and nonsteroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids. Corticosteroids should be used with caution in patients with seizure disorders.
Use in Children: Corticosteroids cause growth retardation in infancy, childhood and adolescence, which may be irreversible. Treatment should be limited to the minimum dosage for the shortest possible time. Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure. High doses of corticosteroids may produce pancreatitis in children.
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.
Systemic corticosteroids are not indicated for, and therefore should not be used to treat traumatic brain injury or stroke because it is unlikely to be of benefit and may even be harmful. A casual association with methylprednisolone sodium succinate treatment has not been established.
Care should be taken with patients receiving cardioactive drugs such as digoxin because of steroid induced electrolyte disturbance/potassium loss. Particular care is required when considering the use of systemic corticosteroid in patients with the following conditions and frequent patient monitoring is necessary.

Pregnancy: The ability of corticosteroids to cross the placenta varies between individual drugs, however, Hydrocortisone readily crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intrauterine growth retardation and affects on brain growth and development. When administered for long periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks.
Some corticosteroids readily cross the placenta. Some retrospective studies have found an increased incidence of low-birth weights in infants born of mothers receiving corticosteroids.
Cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy.
Lactation: Corticosteroids are excreted in breast milk, although no data are available for Hydrocortisone. This medicinal product should be used during breast feeding only after a careful assessment of the benefit-risk ratio to the mother and infant.
Fertility: Corticosteroids have been shown to impair fertility in animal studies. Adverse effects on fertility in rats with corticosteroids were observed in males only and were reversible. The clinical relevance of this information is uncertain.

Since Hydrocortisone sodium succinate for injection is normally employed on a short term basis it is unlikely that side effects will occur; however, the possibility of side effects attributable to corticosteroid therapy should be recognised.
Such side effects include: Parental corticosteroid therapy: Anaphylactoid reaction, e.g. Bronchospasm, hypopigmentation or hyper- pigmentation, subcutaneous and cutaneous atrophy, sterile abscess, laryngeal oedema and urticaria.
Gastrointestinal: Dyspepsia, peptic ulcer with perforation and haemorrhage, abdominal distension, oesophageal ulceration, oesophageal candidiasis, acute pancreatitis, perforation of bowel, Increase in alanine transaminase (ALT/SGPT) aspartate transaminase (AST/SGOT) and alkaline phosphatase have been observed following corticosteroid treatment.
Anti-inflammatory and Immunosuppressive effects: Increased susceptibility and severity of infections with suppression of clinical symptoms and sign, opportunistic infections, may suppress reactions to skin tests, recurrence of dormant tuberculosis.
Musculoskeletal: Proximal myopathy, osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture, aseptic necrosis, muscle weakness.

Convulsions have been reported with concurrent use of corticosteroids and ciclosporin.
Drugs that induce hepatic enzymes, such as rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone, and aminoglutethimide enhance the metabolism of corticosteroids and its therapeutic effects may be reduced.
Drugs which inhibit the CYP3A4 enzyme, such as cimetidine, erythromycin, ketoconazole, itraconazole, diltiazem and mibefradil, may decrease the rate of metabolism of corticosteroids and hence increase the serum concentration.
Steroids may reduce the effects of anticholinesterases in myasthenia gravis. The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids, and the hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced.
The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.
The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.
Salicylates and non-steroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids in hypothrombinaemia.
Steroids have been reported to interact with neuromuscular blocking agents such as pancuronium with partial reversal of the neuromuscular block.

Direction for Use: Dissolve the contents in 2 mL Sterilised Water For Injections for IM / Slow IV Administration & for IV Infusion: Prepare a primary solution as above and then add to 100-1000 mL of 5% dextrose in water.
The reconstituted solution should be used immediately after preparation.
The prepared solution should be used only, if it is clear.

Store at temperatures not exceeding 30°C. Protect from light.

Corticosteroid Hormones

H02AB09 - hydrocortisone ; Belongs to the class of glucocorticoids. Used in systemic corticosteroid preparations.

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