SIGNIFOR

What it is

Signifor is a solution for injection containing pasireotide (as diaspartate) in strengths of 300 micrograms, 600 micrograms, or 900 micrograms per 1 mL. Pasireotide is a cyclohexapeptide, injectable somatostatin analogue. Signifor is administered subcutaneously by self-injection.

Approved indications

— Treatment of adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.

Dosing overview

The recommended dosage range of Signifor is 300 micrograms to 900 micrograms by subcutaneous injection, twice a day. The recommended initial dose is 600 micrograms or 900 micrograms twice a day. Dose should be titrated based on response and tolerability. Maximum urinary free cortisol reduction is typically seen by two months of treatment. For patients with moderately impaired hepatic function (Child-Pugh B), the recommended initial dose is 300 micrograms twice a day.

Key safety warnings

Treatment with Signifor leads to rapid suppression of ACTH secretion in Cushing's disease patients, which may lead to a decrease in circulating cortisol levels and potentially hypocortisolism, with cases reported generally within the first two months of treatment. Elevations in blood glucose levels have been seen in patients treated with Signifor, with nearly all patients developing worsening glycaemia in the first two weeks of treatment. Glycaemic status must be assessed prior to starting treatment and regularly monitored, with self-monitoring of blood glucose or fasting plasma glucose assessments done every week for the first two to three months and periodically thereafter, as well as over the first two to four weeks after any dose increase. Post-marketing cases of ketoacidosis have been reported in patients with and without a history of diabetes, and patients presenting with signs and symptoms of severe metabolic acidosis should be assessed for ketoacidosis regardless of diabetes history. Bradycardia has been reported with pasireotide use, and patients with cardiac disease and risk factors for bradycardia should be carefully monitored. Pasireotide prolongs the QT interval on the ECG and should be used with caution in patients at significant risk of QT prolongation, with baseline ECG recommended prior to initiating therapy. Mild transient elevations in aminotransferases have been commonly observed, and a few cases of concurrent elevations in ALT greater than 3 times the upper limit of normal and bilirubin greater than 2 times the upper limit of normal have been observed, with monitoring of liver function recommended prior to treatment and after the first 1 to 2 weeks and then monthly for 3 months. Cholelithiasis is a recognised adverse reaction associated with long-term use of somatostatin analogues and has been frequently reported in clinical studies with pasireotide, with ultrasonic examination of the gallbladder before and at 6- to 12-month intervals during therapy recommended.

Contraindications

Severe hepatic impairment (Child-Pugh C) is a contraindication to Signifor use.

Regulatory history

The TGA approved the registration of Signifor on 28 October 2013. The 300 microgram, 600 microgram, and 900 microgram solution for injection formulations were first listed on the ARTG on 1 November 2013.