Overview
11 DESCRIPTION SIGNIFOR (pasireotide) injection is prepared as a sterile solution of pasireotide diaspartate in a tartaric acid buffer for administration by subcutaneous injection. SIGNIFOR is a somatostatin analog. Pasireotide diaspartate, chemically known as (2-Aminoethyl) carbamic acid...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action SIGNIFOR is an injectable cyclohexapeptide somatostatin analogue. Pasireotide exerts its pharmacological activity via binding to somatostatin receptors (SSTRs). Five human somatostatin receptor subtypes are known: SSTR 1, 2, 3, 4, and 5. These receptor subtypes are expressed in different tissues under normal physiological conditions. Corticotroph tumor cells from Cushing's disease patients frequently over-express SSTR5 whereas the other receptor subtypes are often not expressed or are expressed at lower levels. Pasireotide binds and activates the SSTRs resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion. The binding affinities of endogenous somatostatin and pasireotide are shown in Table 2.
Indications
- 1 INDICATIONS AND USAGE SIGNIFOR is a somatostatin analog indicated for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative ( 1 ) 1.1 Cushing's Disease SIGNIFOR is indicated for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative.
Common Doses
- 0.6 mg
- 0.9 mg
- 0.3 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended initial dosage is either 0.6 mg or 0.9 mg by subcutaneous injection twice a day; recommended dosage range is 0.3 mg to 0.9 mg twice a day ( 2.1 ) Titrate dosage based on treatment response [clinically meaningful reduction in 24-hour urinary free cortisol (UFC) and/or improvements in signs and symptoms of disease] and tolerability ( 2.1 ) Testing Prior to Dosing : fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), liver tests, electrocardiogram (ECG), gallbladder ultrasound, and serum potassium and magnesium levels ( 2.
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Hypocortisolism [see Warnings and Precautions (5.1)] Hyperglycemia and Diabetes [see Warnings and Precautions (5.2)] Bradycardia and QT prolongation [see Warnings and Precautions (5.3)] Liver Test Elevations [see Warnings and Precautions (5.4)] Cholelithiasis and Complications of Cholelithiasis [see Warnings and Precautions (5.5)] Pituitary Hormone Deficiency [see Warnings and Precautions (5.6)] Steatorrhea and Malabsorption of Dietary Fats [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Drugs that Prolong QT : Use with caution in patients who are at significant risk of developing QTc prolongation ( 5.3 , 7.1 ) Cyclosporine : Consider additional monitoring ( 7.2 ) Bromocriptine : Consider bromocriptine dose reduction ( 7.2 ) 7.1 Effects of Other Drugs on SIGNIFOR Drugs That Prolong QT Coadministration of drugs that prolong the QT interval with SIGNIFOR may have additive effects on the prolongation of the QT interval. Caution is required when coadministering SIGNIFOR with drugs that may prolong the QT interval [see Warnings and Precautions (5.3)] . 7.