About SIGNIFOR | SIGNIFOR® (pasireotide)

How SIGNIFOR works

SIGNIFOR^® (pasireotide) is the first and only subcutaneously administered treatment that works in the pituitary gland to help reduce cortisol and calm the signs and symptoms of Cushing’s disease.

Cushing’s disease is caused by a benign tumor in the pituitary gland, called a pituitary adenoma, that can cause too much hormone production
The pituitary gland is part of the endocrine system that releases hormones that regulate the functions of other endocrine glands
In people who develop this type of tumor, their bodies make too much of a certain hormone called cortisol
Excess cortisol causes the problems associated with Cushing’s disease

SIGNIFOR reduces cortisol levels by targeting key somatostatin (SST) receptors in the pituitary adenoma cells.

SIGNIFOR targets 4 of the 5 SST receptors, and works primarily at SST₅ and SST₂
SST₅ is known to be the most common SST receptor in Cushing’s disease tumors

SIGNIFOR directly targets the pituitary gland tumor

binding to key receptors that are most responsible for excess cortisol to help reduce cortisol levels.

What SIGNIFOR does

Up to 26% of patients achieved normal
cortisol levels in a medical study:

15% who took the 0.6-mg dose twice daily had mean urinary free cortisol levels return to normal, 26% of people who took the 0.9-mg dose twice daily had mean urinary free cortisol levels return to normal

ABOUT THE STUDY: SIGNIFOR 0.6 mg and 0.9 mg were evaluated over a 6-month period in a randomized study in 162 patients with persistent or recurrent Cushing’s disease despite pituitary surgery or patients for whom surgery was not indicated or who had refused surgery.

SIGNIFOR reduced cortisol levels in both treatment groups

Approximately 15%-26% of patients taking SIGNIFOR had their cortisol levels return to normal. Cortisol decreases of approximately 20%-40% were seen in patients even though some did not return to normal.

Weight

Waist circumference

Body mass index

Blood pressure

In studies, individual patients showed different amounts of improvement in the symptoms of Cushing's disease. Because there was not a group who didn't receive the medication, there were different rates of reductions (lowering) of these symptoms, and blood pressure medications were allowed during this trial, it is not known if these changes were from taking SIGNIFOR or not.

SIGNIFOR dosing

for patients with Cushing’s disease

Twice-daily self-administered injection, or injected by a caregiver

When starting SIGNIFOR twice a day at 0.6 mg or 0.9 mg, a dose increase or decrease twice a day may be considered based on how treatment works and tolerability of the starting dose.

With SIGNIFOR you are not required to visit a trained healthcare professional’s office to receive your injection(s)
Your healthcare professional will train you or your caregiver on how to inject SIGNIFOR into your thigh or abdomen
Refer to the SIGNIFOR Instructions for Use for detailed instructions
If you encounter any difficulty giving yourself injection(s), you may receive additional training from a nurse through the R.A.R.E.™ Patient Support Program

Before you take SIGNIFOR, tell your doctor if you:

Have or have had high blood sugar (hyperglycemia)
Have diabetes
Have or have had heart problems
Have a history of low levels of potassium or magnesium in your blood
Have or have had liver problems
Have or have had gallstones
Have any other medical conditions
Are pregnant or plan to become pregnant. SIGNIFOR may harm your unborn baby
Are breastfeeding or plan to breastfeed. It is not known if SIGNIFOR passes into your breast milk. You and your doctor should decide if you will take SIGNIFOR or breastfeed. You should not do both

Treatment with SIGNIFOR may result in improved fertility and the possibility of unplanned pregnancy in women who have Cushing’s disease and have not gone through menopause. Talk to your healthcare provider about birth control methods that may be right for you during treatment with SIGNIFOR.

Tell a healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

SIGNIFOR and other medicines may affect each other, causing side effects. SIGNIFOR may affect the way other medicines work, and other medicines may affect how SIGNIFOR works. Your healthcare provider may need to change your dose of SIGNIFOR or your other medicines. Especially tell your healthcare provider if you take:

Medicines to control your heartbeat (anti-arrhythmics)
Medicines that can affect the electrical system of your heart (QT prolongation)
Medicines to control your blood pressure (such as beta-blockers or calcium channel blockers)
Medicines to control the electrolyte (such as potassium or magnesium) levels in your blood
Cyclosporine
Bromocriptine

Ask your healthcare provider for a list of these medicines if you are not sure.

Know the medicines you take, and keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

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Use SIGNIFOR exactly as your doctor tells you to
Your doctor may change your dose if needed
Before you use SIGNIFOR for the first time, your doctor should do a blood test to check your blood sugar levels and your liver tests
Before you use SIGNIFOR for the first time, your doctor should do a test to check your heart (electrocardiogram) and your gallbladder (ultrasound)
SIGNIFOR should be clear and colorless. Before you inject your dose, check to make sure that SIGNIFOR is clear and colorless, and does not have any clumps or particles in it
SIGNIFOR is given as an injection into the fat just under your skin (subcutaneous injection)
Do not inject SIGNIFOR into skin that is red or irritated
The recommended injection sites for SIGNIFOR are the top of your thigh or stomach area (abdomen)
Change (rotate) your injection site with each dose. Do not inject SIGNIFOR into the exact same spot for each injection
Your doctor should show you how to prepare and give your dose of SIGNIFOR before you use it for the first time
You should not inject SIGNIFOR until your doctor has shown you how to use it the right way
If you take too much SIGNIFOR, tell your doctor right away

If you experience sudden abdominal pain or pain in your right shoulder or between shoulder blades, yellow eyes, fever with chills, weakness, dizziness, or fainting spells, contact your healthcare provider right away.

Read the instructions provided within the Medication Guide section of the full Prescribing Information for SIGNIFOR.

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Diarrhea
Nausea
High blood sugar
Headache
Abdominal pain
Fatigue

Diabetes mellitus
Injection-site reactions
Common cold
Hair loss
Weakness
Fluid retention

There are other serious side effects that can occur with SIGNIFOR. If you experience sudden abdominal pain or pain in your right shoulder or between shoulder blades, yellow eyes, fever with chills, weakness, dizziness, or fainting spells, contact your healthcare provider right away.

To report SUSPECTED SIDE EFFECTS, contact Recordati Rare Diseases Inc. at 1-888-575-8344,
or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

LEARN ABOUT THE R.A.R.E. PATIENT SUPPORT Program

Find resources to help on the treatment journey

SIGNIFOR

How SIGNIFOR works

SIGNIFOR directly targets the pituitary gland tumor

What SIGNIFOR does

Up to 26% of patients achieved normal
cortisol levels in a medical study:

SIGNIFOR reduced cortisol levels in both treatment groups