Signifor

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 (

• 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       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

  (14)]

  . Maximum UFC reduction is typically seen by two months of treatment

  [see Clinical Studies (14)]

  . 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.
  )
  
• 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       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

  (14)]

  . Maximum UFC reduction is typically seen by two months of treatment

  [see Clinical Studies (14)]

  . 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.
  )
  
• Testing Prior to Dosing
  : fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), liver tests, electrocardiogram (ECG), gallbladder ultrasound, and serum potassium and magnesium levels (
  
  
  2.2 Recommendations Prior to Initiation of SIGNIFOR

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

  • fasting plasma glucose (FPG)
    [see Warnings and Precautions (5.2)]
  • hemoglobin A1c (HbA1c)
    [see Warnings and Precautions (5.2)]
  • liver tests
    [see Warnings and Precautions (5.4)]
  • serum potassium and magnesium levels
    [see Warnings and Precautions (5.3)]

  Patients should also have a baseline electrocardiogram (ECG) and gallbladder ultrasound

  [see Warnings and Precautions (5.3, 5.5)]

  .

  Treatment of patients with poorly controlled diabetes mellitus should be intensively optimized with anti-diabetic therapy prior to starting SIGNIFOR

  [see Warnings and Precautions (5.2)]

  .
  )
  
• Patients With Hepatic Impairment
  :
  
  
  • Child-Pugh B:
    Recommended initial dosage is 0.3 mg twice a day and maximum dosage is 0.6 mg twice a day (
    
    
    2.3       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 (8.6)]

    .
    ,
    
    
    8.6       Hepatic Impairment

    Dose adjustment is not required in patients with mild impaired hepatic function (Child-Pugh A), but is required for patients with moderately impaired hepatic function (Child-Pugh B)

    [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)]

    . Avoid the use of SIGNIFOR in patients with severe hepatic impairment (Child-Pugh C).
    )
    
    
  • Child-Pugh C:
     Avoid use in these patients (
    
    
    2.3       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 (8.6)]

    .
    ,
    
    
    8.6       Hepatic Impairment

    Dose adjustment is not required in patients with mild impaired hepatic function (Child-Pugh A), but is required for patients with moderately impaired hepatic function (Child-Pugh B)

    [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)]

    . Avoid the use of SIGNIFOR in patients with severe hepatic impairment (Child-Pugh C).
    )
    
    

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

• Females and Males of Reproductive Potential
  : Advise premenopausal females of the potential for an unintended pregnancy (
  
  
  8.3       Females and Males of Reproductive Potential

  Discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction or normalization of serum cortisol levels in female patients with Cushing's disease treated with pasireotide may lead to improved fertility.
  )
  
• Safety and effectiveness of SIGNIFOR in children under 18 years have not been established (
  
  
  8.4       Pediatric Use

  Safety and effectiveness of SIGNIFOR have not been established in pediatric patients.
  )