(pasireotide) injection, for subcutaneous use
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 (2R,5S,8S,11S,14R,17S,19aS)-11-(4-aminobutyl)-5-benzyl-8-(4-benzyloxybenzyl)-14- (1H-indol-3-ylmethyl)-4,7,10,13,16,19-hexaoxo-17-phenyloctadecahydro-3a,6,9,12,15,18hexaazacyclopentacyclooctadecen-2-yl ester, di[(S)-2-aminosuccinic acid] salt, is a cyclohexapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin.
The molecular formula of pasireotide diaspartate is C58H66N10O9 •2 C4H7NO4 and the molecular weight is 1313.41. The structural formula is:
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.
The recommended dosage range of SIGNIFOR is 0.3 mg to 0.9 mg by subcutaneous injection twice a day. The recommended initial dose is either 0.6 mg or 0.9 mg twice a day. Titrate dose based on response and tolerability.
Patients should be evaluated for a treatment response [clinically meaningful reduction in 24-hour urinary free cortisol (UFC) levels and/or improvement in signs or symptoms of the disease] and should continue receiving therapy with SIGNIFOR as long as benefit is derived [see Clinical Studies]. Maximum urinary free cortisol reduction is typically seen by two months of treatment [see Clinical Studies]. For patients who are started on 0.6 mg twice a day, a dosage increase to 0.9 mg twice a day may be considered based on the response to the treatment, as long as the 0.6 mg dosage is well tolerated by the patient.
Management of suspected adverse reactions may require temporary dose reduction of SIGNIFOR. Dose reduction by 0.3 mg decrements per injection is suggested.
Prior to the start of SIGNIFOR, patients should have baseline levels of the following:
For patients with moderate hepatic impairment (Child-Pugh B), the recommended initial dosage is 0.3 mg twice a day and the maximum dosage is 0.6 mg twice a day. Avoid the use of SIGNIFOR in patients with severe hepatic impairment (Child-Pugh C) [see Use In Specific Populations].
SIGNIFOR is supplied as a sterile solution in a single-dose, 1 mL colorless glass ampule containing pasireotide in 0.3 mg/mL, 0.6 mg/mL, or 0.9 mg/mL strengths for
0.3 mg/mL, 0.6 mg/mL, and 0.9 mg/mL in a single-dose, 1 mL colorless glass ampule.
SIGNIFOR is supplied as a single dose, colorless glass ampule packaged in a box of 60 ampules, arranged in 10 packs of 6 ampules each. The following packaging configurations are available.
Box of 60 ampules - NDC# 0078-0633-20
Box of 60 ampules - NDC# 0078-0634-20
Box of 60 ampules - NDC# 0078-0635-20
Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F), protect from light.
Clinically significant adverse reactions that appear in other sections of the labeling include:
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].
Concomitant administration of cyclosporine with pasireotide may decrease the relative bioavailability of cyclosporine and, therefore, dose adjustment of cyclosporine to maintain therapeutic levels may be necessary.
Coadministration of somatostatin analogues with bromocriptine may increase the blood levels of bromocriptine. Dose reduction of bromocriptine may be necessary.