What is Signifor?

Signifor is a prescription medicine used to treat Cushing’s disease in adults who cannot have surgery or have failed surgery. It is not known if Signifor is safe and effective in children.

Description

SIGNIFOR LAR (pasireotide) for injectable suspension is a long-acting release form of pasireotide pamoate, as powder to be suspended in the provided diluent immediately prior to intramuscular injection. SIGNIFOR LAR contains pasireotide, a somatostatin analog in the form of pasireotide pamoate (pamoic acid salt). Pasireotide is a cyclohexapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin. Pasireotide pamoate has a chemical name of (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,6,9,12,15,18-hexaazacyclopentacyclooctadecen-2-yl ester pamoic acid salt.

The molecular formula of pasireotide pamoate is C58H66N10O9 • C23H16O6 and the molecular weight is 1435.58 g/mol.

The structural formula is:

The drug product consists of pasireotide pamoate uniformly distributed within microspheres which are made of biodegradable copolymers of poly (D,L-lactide-co-glycolide) acids (PLGA).

SIGNIFOR LAR is available in a vial containing the sterile pasireotide pamoate, PLGA microspheres powder, 10 mg, 20 mg, 30 mg, 40 mg, and 60 mg to be reconstituted with the provided 2 mL sterile diluent.

Each vial contains:

Each diluent prefilled syringe contains:

Mechanism of Action

SIGNIFOR LAR is an injectable cyclohexapeptide, somatostatin analog. Pasireotide exerts its pharmacological activity via binding to somatostatin receptors (SSTR). There are 5 known human somatostatin receptor subtypes: SSTR 1, 2, 3, 4, and 5. These receptor subtypes are expressed in different tissues under normal physiological conditions. Somatostatin analogs bind to SSTRs with different potencies. Pasireotide binds with high affinity to 4 of the 5 SSTRs

What is the most important information I should know about Signifor?

Signifor can cause serious side effects, including:

• Low cortisol levels in your blood (hypocortisolism). Tell your doctor right away if you have any signs and symptoms of hypocortisolism. Signs and symptoms of hypocortisolism may include:
  • weakness
  • fatigue
  • loss of appetite
  • nausea
  • vomiting
  • low blood pressure
  • low level of sodium in your blood
  • low blood sugar

  If you get hypocortisolism while taking Signifor, your doctor may change your dose or ask you to stop taking it.

• High blood sugar (hyperglycemia). Your doctor should check your blood sugar level before you start taking Signifor and while you take it. Signs and symptoms of hyperglycemia may include:
  • excessive thirst
  • high urine output
  • increased appetite with weight loss
  • tiredness

  If you get hyperglycemia while taking Signifor, your doctor may give you another medicine to take to lower your blood sugar. Your doctor may also change your dose of Signifor or ask you to stop taking it.

What should I tell my healthcare provider before taking Signifor?

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.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Taking Signifor with certain other medicines can affect each other and cause side effects. Especially tell your doctor if you take:

• medicines to control your heart beat (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 (Gengraf, Neoral, Restasis, Sandimmune)
• bromocriptine (Cycloset, Parlodel)

Ask your doctor for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them to show to your doctor and pharmacist when you get a new medicine.

How should I take Signifor?

• Read the “Instructions for Use” that comes with Signifor.
• 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.

What are the possible side effects of Signifor?

Signifor may cause serious side effects, including:

• See “What is the most important information I should know about Signifor?”
  • slow heart rate (bradycardia). Signifor can cause your heart to beat slower, which may cause you to feel weak, dizzy or even faint. People who have, or have had, heart problems are at higher risk for bradycardia.
  • problems with the electrical system of your heart (QT interval prolongation), which can put you at risk for abnormal heart beats, dizziness, and fainting spells that can be very serious. Call your doctor right away if you experience such spells.
  • elevation of your liver tests. Your doctor should do blood tests to monitor your liver tests while you use Signifor.
  • gallstones (cholelithiasis) and complications that can happen if you have gallstones. Gallstones are a serious but common side effect of Signifor. Possible complications of gallstones include inflammation and infection of the gallbladder. Your doctor should do a test (ultrasound) to check for gallstones before you start using Signifor and while you use it.
    Tell your healthcare provider if you get any of these symptoms.
    • sudden pain in your upper right stomach area (abdomen)
    • yellowing of your skin and whites of your eyes
    • nausea
    • sudden pain in your right shoulder or between your shoulder blades
    • fever with chills

The most common side effects of Signifor include:

• diarrhea
• nausea
• high blood sugar
• headache
• abdominal pain
• fatigue
• diabetes mellitus
• injection-site reactions
• common cold
• hair loss
• weakness
• fluid retention
• Abnormal blood test result for glycosylated hemoglobin (the level of glycosylated hemoglobin indicates the average blood sugar level over the previous months)

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Signifor. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1–800–FDA–1088.

General information about the safe and effective use of Signifor

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Signifor for a condition for which it was not prescribed. Do not give Signifor to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Signifor. If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about Signifor that is written for health professionals.

For more information go to www.SIGNIFOR.com or call 1-877-503-3377.

How should I store Signifor?

• Store Signifor at 68°F to 77°F (20°C to 25°C).
• Keep Signifor out of the light.

Keep Signifor and all medicines out of the reach of children.

What are the ingredients in Signifor?

Active ingredient: Pasireotide

Inactive ingredients: Mannitol, sodium hydroxide, tartaric acid, and water for injection.

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