Warnings and Precautions: Hyperglycemia and Diabetes: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Patients with poor baseline glycemic control are at…+
SIGNIFOR® LAR (pasireotide) for injectable suspension, for intramuscular use
SIGNIFOR LAR is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions:
Hyperglycemia and Diabetes: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia.
A majority of patients, including those with normal glucose tolerance, pre-diabetes and diabetes, experienced increased glucose levels within the first 2 to 3 months of treatment with SIGNIFOR LAR.
Fasting plasma glucose and hemoglobin A1c should be assessed prior to starting treatment with SIGNIFOR LAR. In patients with poorly controlled diabetes mellitus, anti-diabetic treatment should be optimized before SIGNIFOR LAR treatment is started. Blood glucose monitoring should be done weekly for the first 3 months after initiating SIGNIFOR LAR and the first 4 to 6 weeks after dose increases. Periodic monitoring should continue thereafter, as clinically appropriate.
Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic therapy(ies) or adjustment in the dose or type of anti-diabetic therapy(ies) per standard of care. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled, despite medical management, the dose of SIGNIFOR LAR should be reduced or discontinued.
After treatment discontinuation, fasting plasma glucose and hemoglobin A1c should be assessed if indicated. Patients on anti-diabetic therapy discontinuing SIGNIFOR LAR may require more frequent blood glucose monitoring and anti-diabetic dose adjustment to mitigate the risk of hypoglycemia.
Bradycardia and QT Prolongation
Bradycardia has been reported with the use of SIGNIFOR LAR. Patients with cardiac disease and/or risk factor for bradycardia, such as history of clinically significant bradycardia, high-grade heart block, or concomitant use of drugs associated with bradycardia, should be monitored. Adjustments in the dose of drugs known to slow the heart rate (e.g., beta-blockers, calcium channel blockers) and correction of electrolyte disturbances, may be necessary when initiating or during the course of SIGNIFOR LAR treatment.
SIGNIFOR LAR is associated with QT prolongation and should be used with caution in patients who are at significant risk of developing prolongation of the QT interval. A baseline ECG is recommended prior to initiating therapy with SIGNIFOR LAR and periodically while on treatment. Hypokalemia or hypomagnesemia must be corrected prior to initiating SIGNIFOR LAR and should be monitored periodically during therapy.
Liver Test Elevations
Increases in liver enzymes have been observed with SIGNIFOR LAR. ALT or AST elevation greater than 3 times the upper limit of normal (ULN) were observed in 3% of patients and ALT or AST elevation greater than 5 times the upper limit of normal (ULN) were observed in 1% of patients treated with SIGNIFOR LAR.
Assessment of liver function is recommended prior to treatment with SIGNIFOR LAR, and after the first 2 to 3 weeks, then monthly for 3 months. Thereafter, liver function should be monitored as clinically indicated. Patients who develop increased transaminase levels should be monitored until values return to pre-treatment levels. Treatment with SIGNIFOR LAR should be discontinued if signs or symptoms suggestive of clinically significant liver impairment develop.
Adverse reactions associated with SIGNIFOR LAR and occurring in ≥20% of patients were diarrhea, cholelithiasis, hyperglycemia and diabetes mellitus.
Caution is advised when co-administering drugs that prolong the QT interval with SIGNIFOR LAR
The following drugs may require monitoring and possible dose adjustment when used with SIGNIFOR LAR: cyclosporine and bromocriptine
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