Levecortix-100/Levecortix-250 Special Precautions

Levecortix-100: 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.
lmmunosuppressant 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 long-term 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.
Levecortix-250: Undesirable effects may be minimised by using the lowest effective dose for the minimum period. Frequent patient review is required to appropriately titrate the dose against disease activity.
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. 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. Clinical assessment of disease activity may be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids, but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses. Once a daily dose of 30 mg Hydrocortisone is reached, dose reduction should be slower to allow the HPA-axis to recover.
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 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.
Patients should carry 'Steroid Treatment' cards which give clear guidance on the precautions to be taken to minimise risk and which provide details of prescriber, drug, dosage and the duration of treatment.
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. The clinical presentation may often be atypical and may reach an advanced stage before being recognised.
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. Indicated immunization procedures may be undertaken in patients receiving non-immunosuppressive doses of corticosteroids.
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. Chickenpox is of serious concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. Passive immunization with varicella/zoster immunogloblin (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 immuneglobulin 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. 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.
Allergic reactions may occur. Rarely skin reactions and anaphylactic/anaphylactoid reactions have been reported following parenteral hydrocortisone therapy. Physicians using the drug should be prepared to deal with such a possibility. Appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of drug allergy.
Care should be taken for patients receiving cardioactive drugs such as digoxin because of steroid induced electrolyte disturbance/potassium loss.
Hepatobiliary disorders have been reported which may be reversible after discontinuation of therapy monitoring is required. Hydrocortisone may have an increased effect in patients with liver diseases since the metabolism and elimination of hydrocortisone is significantly decreased in these patients.
Ocular Effects: Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos, or increased intraocular pressure, which may result in glaucoma with possible damage to the optic nerves. 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. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Central serous chorioretinopathy may lead to retinal detachment.
Severe medical events have been reported in association with the intrathecal/epidural routes of administration. There have been reports of epidural lipomatosis in patients taking corticosteroids, typically with long-term use at high doses.
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.
The role of corticosteroids in septic shock has been controversial, with early studies reporting both beneficial and detrimental effects. More recently, supplemental corticosteroids have been suggested to be beneficial in patients with established septic shock who exhibit adrenal insufficiency. However, their routine use in septic shock is not recommended. A systematic review of short-course, high-dose corticosteroids did not support their use. However, meta-analyses, and a review suggest that longer courses (5-11 days) of low-dose corticosteroids might reduce mortality, especially in patients with vasopressor-dependent septic shock.
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. Pharmacologic doses of corticosteroids administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression (secondary adrenocortical insufficiency). The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose, frequency, time of administration, and duration of glucocorticoid therapy. In addition, acute adrenal insufficiency leading to a fatal outcome may occur if glucocorticoids are withdrawn abruptly. Drug-induced secondary adrenocortical insufficiency may therefore be minimized by 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 that period, hormone therapy should be reinstituted. 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. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels. Because glucocorticoids can produce or aggravate Cushing's syndrome, glucocorticoids should be avoided in patients with Cushing's disease. 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. Accordingly, corticosteroids should be employed judiciously in such patients and attention should be paid to risk modification and additional cardiac monitoring if needed. Low dose therapy may reduce the incidence of complications in corticosteroid therapy. 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.
Osteoporosis is generally associated with long-term use and large doses of glucocorticoids. 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 long-term corticosteroid therapy to diabetes mellitus (or a family history of diabetes).
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. Dietary salt restriction and potassium supplementation may be necessary. 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. Symptoms typically emerge within a few days or weeks of starting treatment. Risks may be higher with high doses/systemic exposure that can increase the risk of side effects, although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.
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. There is no universal agreement on whether corticosteroids per se are responsible for peptic ulcers encountered during therapy; however, glucocorticoid therapy may mask the symptoms of peptic ulcer so that perforation or hemorrhage may occur without significant pain. Glucocorticoid therapy may mask peritonitis or other signs or symptoms associated with gastrointestinal disorders such as perforation, obstruction or pancreatitis. In combination with nonsteroidal anti-inflammatory drugs (NSAIDs), the risk of developing gastrointestinal ulcers is increased.
Other: 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 as to whether daily or intermittent therapy should be used.
The lowest possible dose of corticosteroid should be used to control the condition under treatment and when reduction in dosage is possible, the reduction should be gradual.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
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.
Excipient information: This medicinal product contains 10.1 mg of sodium, equivalent to 0.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
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. The use of steroids should be restricted to the most serious indications. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. Growth may be suppressed in children receiving long-term, daily-divided dose glucocorticoid therapy. The use of such a regimen should be restricted to the most serious indications. Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure. High doses of corticosteroids may produce pancreatitis in children.
Hypertrophic cardiomyopathy was reported after administration of hydrocortisone to prematurely born infants, therefore appropriate diagnostic evaluation and monitoring of cardiac function and structure should be performed.
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. For traumatic brain injury a multicenter study revealed an increased mortality at 2 weeks and 6 months after injury in patients administered methylprednisolone sodium succinate compared to placebo. A causal association with methylprednisolone sodium succinate treatment has not been established.