SIGNIFOR
(pasireotide) injection, for subcutaneous use

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 (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:

INDICATIONS

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.

DOSAGE AND ADMINISTRATION

Recommended Dosage Range

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.

Recommendations Prior To Initiation Of Signifor

Prior to the start of SIGNIFOR, patients should have baseline levels of the following:

• fasting plasma glucose [see WARNINGS AND PRECAUTIONS]
• hemoglobin A1c [see WARNINGS AND PRECAUTIONS]
• liver tests [see WARNINGS AND PRECAUTIONS]
• serum potassium and magnesium levels [see WARNINGS AND PRECAUTIONS]

Patients should also have a baseline electrocardiogram and gallbladder ultrasound [see WARNINGS AND PRECAUTIONS].

Treatment of patients with poorly controlled diabetes mellitus should be intensively optimized with anti-diabetic therapy prior to starting SIGNIFOR [see WARNINGS AND PRECAUTIONS].

Dosage In Patients With Hepatic Impairment

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

HOW SUPPLIED

Dosage Forms And Strengths

Injection

0.3 mg/mL, 0.6 mg/mL, and 0.9 mg/mL in a single-dose, 1 mL colorless glass ampule.

Storage And Handling

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.

0.3 mg/1 mL Pasireotide (as diaspartate)

Box of 60 ampules - NDC# 0078-0633-20

0.6 mg/1 mL Pasireotide (as diaspartate)

Box of 60 ampules - NDC# 0078-0634-20

0.9 mg/1 mL Pasireotide (as diaspartate)

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.

SIDE EFFECTS

Clinically significant adverse reactions that appear in other sections of the labeling include:

• Hypocortisolism [see WARNINGS AND PRECAUTIONS]
• Hyperglycemia and Diabetes [see WARNINGS AND PRECAUTIONS]
• Bradycardia and QT prolongation [see WARNINGS AND PRECAUTIONS]
• Liver Test Elevations [see WARNINGS AND PRECAUTIONS]
• Cholelithiasis and Complications of Cholelithiasis [see WARNINGS AND PRECAUTIONS]
• Pituitary Hormone Deficiency [see WARNINGS AND PRECAUTIONS]