SIGNIFOR (pasireotide diaspartate)

In healthy volunteers, pasireotide demonstrates approximately linear pharmacokinetics (PK) for a dose range from 0.0025 to 1.5 mg. In Cushing's disease patients, pasireotide demonstrates linear dose-exposure relationship in a dose range from 0.3 mg to 1.2 mg. Absorption and

DistributionIn healthy volunteers, pasireotide peak plasma concentration is reached within T max 0.25-0.5 hour. C max and AUC are dose-proportional following administration of single and multiple doses. No studies have been ...

A Phase III, multicenter, randomized study was conducted to evaluate the safety and efficacy of two dose levels of SIGNIFOR over a 6-month treatment period in Cushing's disease patients with persistent or recurrent disease despite pituitary surgery or de novo patients for whom surgery was not indicated or who had refused surgery. Patients with a baseline 24-hour urine free cortisol (UFC) >1.5 x ULN were randomized to receive a SIGNIFOR dosage of either 0.6 mg subcutaneous twice a day or 0.9 mg subcutaneous twice a day. After 3 months of treatment, patients with a mean 24-hour UFC ≤ 2.0 x ULN a...

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)] Steat...

None. None ( 4 )

Hypocortisolism : Decreases in circulating levels of cortisol may occur resulting in biochemical and/or clinical hypocortisolism. SIGNIFOR dose reduction or interruption and/or adding a low-dose short-term glucocorticoid may be necessary ( 5.1 ) Hyperglycemia and Diabetes (occurs with initiation) : Intensive glucose monitoring is recommended and may require initiation or adjustment of anti-diabetic treatment per standard of care ( 5.2 ) Bradycardia and QT Prolongation : Use with caution in at-ri...

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...