Signifor LAR

What is Signifor LAR?

Signifor LAR is a prescription medicine used to treat people with acromegaly for whom surgery has not worked well enough or who cannot have surgery and Cushing’s disease for whom surgery has not worked well enough or who cannot have surgery.

It is not known if Signifor LAR is safe and effective for use 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.

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 should I tell my healthcare provider before using Signifor LAR?

Before you receive Signifor LAR, tell your healthcare provider about all of your medical conditions, including if you:

• have high blood sugar (hyperglycemia).
• have diabetes.
• have or have had heart problems, including an abnormal heart rate or rhythm or problems with the electrical system of your heart (QT prolongation).
• have a low level of potassium or magnesium in your blood.
• have liver problems.
• have gallstones (cholelithiasis).
• are pregnant or plan to become pregnant. It is not known if Signifor LAR will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if SIGINFOR LAR passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Signifor LAR.

Treatment with Signifor LAR may result in improved fertility and the possibility of unplanned pregnancy in females who have acromegaly or 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 LAR.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Signifor LAR and other medicines may affect each other, causing side effects. Signifor LAR may affect the way other medicines work, and other medicines may affect how Signifor LAR works. Your healthcare provider may need to change your dose of Signifor LAR or your other medicines. Especially tell your healthcare provider if you take:

• medicines to control your heart beat (antiarrhythmics)
• medicines to control your blood pressure (such as beta-blockers or calcium channel blockers)
• medicines to control the potassium and magnesium (electrolytes) levels in your body
• medicines that may affect the way the electrical system of your heart works (QT prolongation)
• cyclosporine
• bromocriptine

Ask your healthcare provider 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 healthcare provider and pharmacist when you get a new medicine.

How should I use Signifor LAR?

• Signifor LAR must be given by a trained healthcare provider as an injection into the muscle of your buttocks (intramuscularly).
• Your healthcare provider will tell you how much Signifor LAR you will receive and when you will receive it.
• Your healthcare provider may change your dose of Signifor LAR or the length of time between your injections. Your healthcare provider will tell you how long you need to receive Signifor LAR.
• Before you receive Signifor LAR for the first time, your healthcare provider should do a blood test to check your fasting blood sugar level, hemoglobin A1c level, electrolyte levels, and your liver function.
• You will need to check your blood sugar levels during treatment with Signifor LAR, especially after you start treatment with Signifor LAR and after your dose is increased. Your healthcare provider will tell you how often you should check your blood sugar levels.
• Before you receive Signifor LAR for the first time and during your treatment, your healthcare provider should do a test to check your heart (electrocardiogram).
• If you miss a dose of Signifor LAR, you may receive your missed dose up to 14 days before your next dose.
• It is important that you keep your scheduled appointments with your healthcare provider during treatment with Signifor LAR.

What are the possible side effects of Signifor LAR?

Signifor LAR may cause serious side effects, including:

• high blood sugar (hyperglycemia) and diabetes. High blood sugar and diabetes are serious but common side effects of Signifor LAR. Your healthcare provider should check your blood sugar level before you start receiving Signifor LAR and while you receive it. Tell your healthcare provider if you have any of these symptoms:
  • feel very thirsty
  • urinate more than usual
  • increased appetite with weight loss
  • tirednessIf you get hyperglycemia while receiving Signifor LAR, your healthcare provider may give you another medicine to lower your blood sugar. Your healthcare provider may also change your dose of Signifor LAR or advise you to stop receiving it.
• slow heart rate (bradycardia). Signifor LAR can cause your heart to beat slower. People who have, or have had heart problems, or take certain medicines used to treat slow heart rate or that may cause a slow heart rate, are at higher risk for bradycardia. Tell your healthcare provider if you get any of these symptoms:
  • weakness
  • dizziness
  • fainting or near fainting spells
• changes in the electrical system of your heart (QT interval prolongation). Tell your healthcare provider if you get any of these symptoms:
  • weakness
  • dizziness
  • fainting or near fainting spells
• higher than normal liver function tests. Your healthcare provider should do blood tests to check your liver while you receive Signifor LAR.
• gallstones (cholelithiasis) and complications that can happen if you have gallstones. Gallstones are a serious but common side effect of Signifor LAR. Possible complications of gallstones include inflammation and infection of the gall bladder. Your healthcare provider should do a test (ultrasound) to check your gall bladder before and during your treatment with Signifor LAR. Tell your healthcare provider if you get any of these symptoms:
  • sudden pain in your upper right stomach area (abdomen)
  • sudden pain in your right shoulder or between your shoulder blades
  • yellowing of your skin and whites of your eyes
  • fever with chills
  • nausea
• low levels of pituitary hormones (pituitary insufficiency). Signifor LAR may reduce the pituitary hormones in your body. Your healthcare provider should do a blood test to check your pituitary hormone levels before you start receiving Signifor LAR and while you receive it. Tell your healthcare provider if you get any of these symptoms:
  • nausea and vomiting
  • tiredness
  • dizziness
  • diarrhea
  • low blood sugar levels
  • loss of appetite
  • weight loss

The most common side effects of Signifor LAR include:

• diarrhea
• headache
• stomach-area pain
• hair loss
• stuffy nose and sore throat
• low blood sugar
• limb swelling
• loss of appetite
• nausea
• increase in the level of an enzyme in your blood called creatine phosphokinase (CPK)
• tiredness
• stomach bloating
• high blood pressure
• back pain

Tell your healthcare provider 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 LAR. For more information, ask your healthcare provider 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 LAR

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

This Patient Information leaflet summarizes the most important information about Signifor LAR. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about Signifor LAR that is written for health professionals.

For more information go to www.SIGNIFORLAR.com or call 1-888-NOW-NOVA.

How should I store Signifor LAR?

• Store Signifor LAR in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze Signifor LAR.
• Take Signifor LAR out of the refrigerator at least 30 minutes before you will receive it to allow it to come to room temperature.
• Do not use Signifor LAR if it has been out of the refrigerator and at room temperature for more than 24 hours.
• Your healthcare provider should give you Signifor LAR right away after it is mixed.

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

What are the ingredients in Signifor LAR?

Active ingredient: pasireotide pamoate

Inactive ingredients:

Vial: Poly(D,L-lactide-co-glycolide)

Prefilled syringe: Mannitol, carboxymethylcellulose sodium, poloxamer 188, and water for injections

Label

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