Pasireotide

Bradycardia and QT prolongation have been observed with therapy. Use with caution in patients with preexisting cardiac disease, patients with risk factors for bradycardia (eg, high-grade heart block, history of significant bradycardia, receiving concomitant drugs known to cause bradycardia), and/or patients at risk for QT prolongation (eg, congenital long QT, recent MI, heart failure, unstable angina, hypokalemia, hypomagnesemia, receiving concomitant drugs known to cause QT prolongation). Obtain baseline electrocardiogram (ECG) prior to therapy and consider continued monitoring during therapy for an effect on the QTc interval. Correct hypokalemia, hypomagnesemia, and/or hypocalcemia prior to therapy and monitor during therapy.

May impair gallbladder, leading to gallstone formation; monitor patients for cholelithiasis.

Increased liver enzymes have been reported; ALT, AST, and bilirubin should be monitored per recommendations in manufacturer’s labeling. May require dosage interruption to investigate probable cause of confirmed or rising liver enzyme values; patients with significant elevations in liver function tests require more frequent monitoring and extensive monitoring (ALT, AST, alkaline phosphatase, total bilirubin).

Inhibition of insulin and glucagon secretion may affect glucose regulation, leading to hyperglycemia (sometimes severe). Exacerbation of glycemia occurred in the majority of patients during the initial months of therapy, including patients with normal glucose levels at baseline; diabetes and prediabetes has also been observed. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. Assess fasting blood glucose (FBG) levels and/or hemoglobin A1c (HbA1c) prior to initiation of therapy. Patients should also do self-monitoring of blood glucose and/or FBG for the first few months of therapy, after dose increases, and periodically during use. If hyperglycemia occurs, initiation or dosage adjustment of antidiabetic therapy is recommended; if uncontrolled hyperglycemia persists despite antidiabetic therapy, consider dosage reduction or discontinuation of pasireotide.

Suppression of the adrenocorticotropic hormone (ACTH) from therapy may lead to hypocortisolism in Cushing disease. Monitor all patients for signs or symptoms of hypocortisolism (eg, anorexia, fatigue, hypoglycemia, hyponatremia, hypotension, nausea, vomiting, weakness). If symptoms occur, consider stopping or reducing the dose until symptoms improve. Glucocorticoid replacement therapy may also be needed temporarily.

Decreases (slight) in thyroid function have been observed during therapy; monitor thyroid function tests prior to therapy and periodically during therapy. Disease-related concerns:

Prior to initiation, patients with poorly controlled or uncontrolled diabetes should have antidiabetic therapy optimized; exacerbation of glycemia commonly occurs with pasireotide use.

Use with caution in patients with hepatic impairment; lower doses are recommended at therapy initiation in patients with moderate impairment (Child-Pugh class B). Use not recommended in patients with severe impairment (Child-Pugh class C). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Acromegaly: Signifor LAR: For intramuscular (IM) use; do not administer intravenously (IV). Must be reconstituted and administered by a trained health care provider. Therapy may cause inhibition of additional pituitary hormones (other than GH/IGF-1); additional monitoring for pituitary deficiency is advised (eg, thyroid, adrenal, gonadal) prior to initiation of therapy and periodically thereafter.

Cushing disease: Signifor: For subcutaneous injection. Evaluate for treatment response with 24-hour urinary free cortisol levels and/or improvement in symptoms. Maximum reduction in urinary free cortisol levels is usually seen by 2 months of therapy. Therapy may cause inhibition of additional pituitary hormones (other than ACTH); additional monitoring for pituitary deficiency is advised (eg, thyroid-stimulating hormone [TSH], free T4, GH, IGF-1), particularly in patients who have undergone transsphenoidal surgery and pituitary irradiation who are at an increased risk for deficiency.