Signifor (pasireotide) is indicated for adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.
Signifor (pasireotide) intramuscular injection is indicated for adult patients with acromegaly for whom surgery is not an option or has not been curative and who are inadequately controlled on treatment with a first-generation somatostatin analogue (SSA).
This information is based on the European Summary of Product Characteristics. The prescribing information in your country may vary; please consult your local prescribing information and/or contact your local Novartis representative.
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Important Safety Information about Signifor
Signifor is contraindicated in patients with hypersensitivity to the active substances in Signifor or to any of the excipients and in patients with severe liver impairment.
Alterations in blood glucose levels have been frequently reported in healthy volunteers and patients treated with Signifor. Glycemic status should be assessed prior to starting treatment with Signifor. Patients need to be monitored for hyperglycemia; if hyperglycemia develops, the initiation or adjustment of antidiabetic treatment is recommended. Dose reduction or treatment discontinuation should be considered if uncontrolled hyperglycemia persists. After treatment discontinuation, glycemic monitoring (e.g. FPG or HbA1c) should be done according to clinical practice.
Monitoring of liver function is recommended prior to starting treatment with Signifor and after one, two, four, eight and twelve weeks during treatment and thereafter as clinically indicated. Therapy should be discontinued if the patient develops jaundice, other clinical signs of significant liver dysfunctions, sustained AST (aminotransferases) or ALT (alanine aminotransferase) increase five times the upper limit of normal (ULN) or greater, or if ALT or AST increase three times ULN with concurrent bilirubin elevation greater than two times ULN.
Patients with cardiac disease and/or risk factors for bradycardia need to be closely monitored. Caution is to be exercised in patients who have or may develop QT prolongation. Hypokalemia or hypomagnesemia must be corrected prior to initiating therapy and monitored thereafter. Electrocardiography should be performed prior to the start of Signifor therapy and as clinically indicated thereafter.
Treatment with Signifor leads to rapid suppression of adrenocorticotropic hormone (ACTH) secretion in Cushing’s disease patients. Patients need to be monitored and instructed how to monitor for signs and symptoms of hypocortisolism. Temporary exogenous steroid (glucocorticoid) replacement therapy and/or dose reduction or interruption of Signifor therapy may be necessary.
Monitoring of gallbladder and pituitary hormones is recommended prior to initiating treatment and periodically thereafter.
Signifor should not be used during pregnancy unless clearly necessary. Breast feeding should be discontinued during treatment with Signifor.
Signifor may affect the way other medicines work, and other medicines can affect how Signifor works. Caution is to be exercised with the concomitant use of drugs with low therapeutic index mainly metabolized by CYP3A4, bromocriptine, cyclosporine, anti-arrhythmic medicines or drugs that may lead to QT prolongation.
The most frequently reported adverse events (AE) (>10%) by investigators for Signifor were diarrhea, nausea, hyperglycemia, cholelithiasis, abdominal pain, diabetes mellitus, injection site reactions, fatigue and increased glycosylated hemoglobin (HbA1c), with most events being Grade 1-2. The tolerability profile of Signifor was similar to that of other somatostatin analogs with the exception of the greater degree of hyperglycemia.
Important safety information about Signifor (pasireotide) intramuscular injection
Signifor is contraindicated in patients with severe hepatic impairment (Child Pugh C).
Hyperglycemia and diabetes occurs with initiation of Signifor therapy. Acromegaly patients with poor glycemic control (as defined by hemoglobin A1c (HbA1c) values >8% while receiving anti-diabetic therapy) may be at a higher risk of developing severe hyperglycemia and associated complications, e.g., ketoacidosis. Intensive glucose monitoring is recommended and may require initiation or adjustment of anti-diabetic treatment.
Treatment with Signifor may lead to bradycardia and QT prolongation. Caution should be used in at-risk patients. ECG testing is recommended prior to dosing and during treatment. Hypokalemia and hypomagnesemia must be corrected prior to Signifor administration and should be monitored periodically during therapy.
Mild transient elevations in aminotransferases are commonly observed in patients treated with pasireotide. Liver tests are recommended prior to and after the first 2 to 3 weeks on treatment, then monthly for 3 months, and as clinically indicated thereafter.
Cholelithiasis is associated with Signifor. Gallbladder ultrasounds should be performed before and at 6- to 12- month intervals.
Inhibition of pituitary hormones may occur with Signifor treatment. Monitoring of pituitary function should occur prior to initiation of therapy and periodically during treatment with Signifor.
Treatment with Signifor may lead to a decrease in circulating levels of cortisol resulting in biochemical and/or clinical hypocortisolism. Signifor dose of reduction or interruption and/or adding low-dose short-term glucocorticoid therapy may be necessary.
Caution is required when co-administering Signifor with anti-arrhythmics and drugs that prolong QT. The following drugs may require monitoring and possible dose adjustments when used with Signifor: cyclosporine, bromocriptine.
The most common adverse reactions (≥10%) occurring in patients in acromegaly clinical trials are hyperglycemia, diabetes mellitus, diarrhea, abdominal pain, cholelithiasis and alopecia.