Patient Information Leaflet

Signifor 10mg powder and solvent for injection

Signifor 20mg powder and solvent for injection

Signifor 30mg powder and solvent for injection

Signifor 40mg powder and solvent for injection

Signifor 60mg powder and solvent for injection

pasireotide

Read this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, nurse or pharmacist, even if they are not listed in this leaflet. See section4.

1.What isSigniforand what it is used for

2.What you need to know before starting to useSignifor

3.How to useSignifor

4.Possible side effects

5.Storage ofSignifor

6.Contents of the pack and additional information

Signifor is a medication that contains the active ingredient pasireotide. It is used to treat acromegaly in adult patients. It is also used to treat Cushing's disease in adult patients for whom surgery is not an option or has failed.

Acromegaly

Acromegaly is caused by a type of tumor called a pituitary adenoma, which appears in the pituitary gland at the base of the brain. The adenoma causes the body to produce an increased amount of hormones that control tissue, organ, or bone growth, resulting in an increase in the size of bones and tissues, especially in the hands and feet.

Signifor reduces the production of these hormones and possibly also the size of the adenoma. As a result, it reduces the symptoms of acromegaly, which include headache, increased sweating, numbness in the hands and feet, fatigue, and joint pain.

Cushing's Disease

Cushing's disease is caused by an enlargement of the pituitary gland (a gland located at the base of the brain) called a pituitary adenoma. This causes the body to produce an increased amount of a hormone called adrenocorticotropic hormone (ACTH), which in turn causes an increase in the production of another hormone called cortisol.

The human body naturally produces a substance called somatostatin, which blocks the production of certain hormones, including ACTH. Pasireotide works in a very similar way to somatostatin. Signifor is therefore able to block the production of ACTH, helping to control the overproduction of cortisol and improve the symptoms of Cushing's disease.

If you have any doubts about how Signifor works or why you have been prescribed this medication, consult with your doctor.

No use Signifor:

• If you are allergic to pasireotide or any of the other components of this medication (listed in section6).
• If you have severe liver problems.

Advertencias y precauciones

Consult your doctor before starting to use Signifor if you suffer or have ever suffered from:

• problems with blood sugar levels, either too high (such as in hyperglycemia/diabetes) or too low (hypoglycemia);
• heart problems such as a recent heart attack, congestive heart failure (a type of heart disease where the heart cannot pump enough blood through the body) or sudden and oppressive chest pain (usually felt as pressure, heaviness, oppression, compression, or pain in the entire chest);
• an alteration of the heart rhythm, such as irregular heartbeat or an abnormal electrical signal called "prolongation of the QT interval," or "QT prolongation";
• low levels of potassium or magnesium in the blood;
• gallstones;
• or if you are taking anticoagulants (medications used to reduce the ability of the blood to clot), your doctor will monitor your coagulation parameters and may adjust your anticoagulant dose.

Durante su tratamiento con Signifor

• Signifor may cause an increase in blood sugar levels. Your doctor may monitor your blood sugar levels and start treatment or adjust your antidiabetic medication.
• Signifor controls excessive cortisol production. The control may be too strong and may present signs or symptoms associated with a lack of cortisol, such as extreme weakness, fatigue, weight loss, nausea, vomiting, or low blood pressure. If this happens, immediately inform your doctor.
• Signifor may reduce your heart rate. Your doctor may monitor your heart rate using a machine that measures the electrical activity of the heart (an "ECG," or electrocardiogram). If you are taking a medication to treat a heart problem, your doctor may also need to adjust your dose.
• Your doctor may also periodically monitor your gallbladder, liver enzymes, and pituitary hormones, as they may be affected by this medication.

Niños y adolescentes

Do not give this medication to children and adolescents under 18years because there are no available data in this age group.

Otros medicamentos y Signifor

Signifor may affect the way other medications work. If you are taking other medications at the same time as Signifor (including over-the-counter medications), your doctor may need to monitor your heart more closely or change the dose of Signifor or the other medications. Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication. Especially, inform your doctor if you are taking:

• medications used in organ transplantation to reduce the activity of the immune system (ciclosporina);

• medications to treat high blood sugar levels (such as in diabetes) or low blood sugar levels (hypoglycemia) such as:

• insulin
• metformin, liraglutide, vildagliptin, nateglinide (diabetes medications);

• medications to treat irregular heart rhythms, such as those containing disopyramide, procainamide, quinidine, sotalol, dofetilide, ibutilide, amiodarone, or dronedarone;
• medications to treat bacterial infections (oral: clarithromycin, moxifloxacin; injectable: erythromycin, pentamidine);
• medications to treat fungal infections (ketoconazole, except in shampoo);
• medications to treat some psychiatric disorders (chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, tiapride, amisulpride, sertindole, methadone);
• medications to treat hay fever and other allergies (terfenadine, astemizole, mizolastine);
• medications used to prevent or treat malaria (chloroquine, halofantrine, lumefantrine);
• medications to control blood pressure such as:

• beta blockers (metoprolol, carteolol, propranolol, sotalol)
• calcium channel blockers (bepridil, verapamil, diltiazem)
• cholinesterase inhibitors (rivastigmine, physostigmine);

• medications to control the balance of electrolytes (potassium, magnesium) in the body.

Embarazo, lactancia y fertilidad

Consult your doctor or pharmacist before using any medication.

• Do not use Signifor during pregnancy unless it is clearly necessary. If you are pregnant or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.
• If you are breastfeeding, consult your doctor before taking this medication, as it is unknown whether Signifor passes into breast milk.
• If you are a sexually active woman, you should use an effective contraceptive method during treatment. Consult your doctor about the need for contraception before using this medication.

Conducción y uso de máquinas

Signifor may have a small effect on your ability to drive and use machines, as some of the adverse effects you may experience while taking Signifor, such as headache, dizziness, and fatigue, may reduce your ability to drive and use machines safely.

Información importante sobre alguno de los componentes de Signifor

Signifor contains less than 1mmol of sodium (23mg) per dose; this is, essentially“exempt from sodium”.

This medication will only be administered by a trained healthcare professional.

How much Signifor to use

Acromegaly

The recommended starting dose of Signifor in acromegaly is 40 mg every 4 weeks. After starting treatment, your doctor may reevaluate your dose. This may involve measuring growth hormone or other hormone levels in your body. Depending on the results and how you feel, it may be necessary to reduce or increase the dose of Signifor administered in each injection. The dose should not exceed 60 mg. If you have liver disease before starting treatment with Signifor, your doctor may decide to start treatment with a dose of 20 mg.

Cushing's disease

The normal starting dose of Signifor in Cushing's disease is 10 mg every 4 weeks. After starting treatment, your doctor may review the dose. This may involve measuring cortisol levels in the blood or urine. Depending on the results and how you feel, the dose of Signifor administered in each injection may be reduced or increased. The dose should not exceed 40 mg.

Your doctor will regularly monitor how you respond to treatment with Signifor and decide what dose is best for you.

How to use Signifor

Your doctor or nurse will administer Signifor. If you have any doubts, consult your doctor, nurse, or pharmacist.

Signifor is used by intramuscular injection. This means it is injected through a needle into the muscles of your buttocks.

For how long to use Signifor

This is a long-term treatment, possibly lasting years. Your doctor will regularly monitor your condition to check that the treatment is having the desired effect. Your treatment with Signifor should continue as long as your doctor tells you it is necessary.

If you stop using Signifor

If you stop your treatment with Signifor, your symptoms may return. Therefore, do not stop your treatment with Signifor unless your doctor tells you to.

If you have any other questions about using this medication, ask your doctor, nurse, or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some side effects can be serious. Inform your doctor immediately if you experience any of the following side effects:

Very common (may affect more than 1 in 10 patients)

• High blood sugar levels. You may notice excessive thirst, urination, increased appetite with weight loss, fatigue, nausea, vomiting, abdominal pain.
• Gallstones or associated complications. You may experience fever, chills, yellowish discoloration of the skin/eyes, sudden back pain or right-sided abdominal pain.

Common (may affect up to 1 in 10 patients)

• Low cortisol levels. You may present extreme weakness, fatigue, weight loss, nausea, vomiting, and low blood pressure.
• Slow heart rate.
• Prolonged QT interval (an altered electrical signal in your heart that can be seen in tests).
• Bile flow problems (cholestasis). You may present yellowish discoloration of the skin, dark urine, pale stools, and itching.
• Gallbladder inflammation (cholecystitis).

Other side effects of Signifor may include:

Very common (may affect more than 1 in 10 patients)

-Diarrhea

• Nausea
• Abdominal pain
• Fatigue

Common (may affect up to 1 in 10 patients)

• Fatigue, pallor in the skin (signs of low red blood cell count)
• Loss of appetite
• Headache
• Swelling
• Vomiting
• Dizziness
• Pain, discomfort, itching, and swelling at the injection site
• Changes in liver function test results
• Abnormal blood test results (sign of elevated creatine phosphokinase, hemoglobin A1c, lipase in the blood)
• Hair loss

Rare (may affect up to 1 in 100 patients)

• Changes in pancreatic function test results (amylase)
• Abnormal blood clotting properties

Unknown frequency (cannot be estimated from available data)

• Elevated ketone bodies (a group of substances produced in the liver) in the urine or blood (diabetic ketoacidosis) as a complication of high blood sugar levels. You may present fruity-smelling breath, breathing problems, and confusion.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box, vial, and preloaded syringe after«EXP»/«CAD». The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2°C and 8°C). Do not freeze.
• Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Signifor

• The active ingredient is pasireotide.

Signifor 10mg: each vial contains 10mg of pasireotide (as pasireotide pamoate)

Signifor 20mg: each vial contains 20mg of pasireotide (as pasireotide pamoate)

Signifor 30mg: each vial contains 30mg of pasireotide (as pasireotide pamoate)

Signifor 40mg: each vial contains 40mg of pasireotide (as pasireotide pamoate)

Signifor 60mg: each vial contains 60mg of pasireotide (as pasireotide pamoate)

• The other components are:
• • In the powder: poly(D,L-lactide-co-glycolide) (50‑60:40.50), poly(D,L-lactide-co-glycolide) (50:50).
  • In the solvent: sodium carmellose, mannitol, poloxamer 188, water for injection.

Appearance of Signifor and contents of the pack

Signifor powder is a light yellow to yellow powder in a vial. The solvent is a transparent, colourless to slightly yellow or slightly brown solution in a pre-filled syringe.

Signifor 10mg is available in single-dose packs containing a vial of powder with 10mg of pasireotide and a pre-filled syringe with 2ml of solvent.

Signifor 20mg is available in single-dose packs containing a vial of powder with 20mg of pasireotide and a pre-filled syringe with 2ml of solvent.

Signifor 30mg is available in single-dose packs containing a vial of powder with 30mg of pasireotide and a pre-filled syringe with 2ml of solvent.

Signifor 40mg is available in single-dose packs containing a vial of powder with 40mg of pasireotide and a pre-filled syringe with 2ml of solvent.

Signifor 60mg is available in single-dose packs containing a vial of powder with 60mg of pasireotide and a pre-filled syringe with 2ml of solvent.

Each single-dose pack contains the vial and the pre-filled syringe in a blister pack sealed with an adapter to the vial and a safety needle.

Signifor 40mg and Signifor 60mg are also available in multi-dose packs containing 3intermediate packs.

It may be that, in your country, only some doses and some pack sizes are marketed.

Marketing authorisation holder

Recordati Rare Diseases

Immeuble Le Wilson

70 avenue du Général de Gaulle

92800 Puteaux

France

Responsible for manufacturing

Recordati Rare Diseases

Immeuble Le Wilson

70 avenue du Général de Gaulle

92800 Puteaux

France

Recordati Rare Diseases

Eco River Parc

30 rue des Peupliers

92000 Nanterre

France

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan medicines.

This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR USE OF SIGNIFOR POWDER AND SOLVENT FOR INJECTABLE SUSPENSION

ONLY FOR INTRAMUSCULAR DEEP INJECTION

The injection kit includes:

aA vial containing the powder

bA pre-filled syringe containing the solvent

cAn adapter to the vial for reconstituting the medicine

dA safety needle (20Gx1,5”)

Follow the detailed instructions below to ensure the proper reconstitution of Signifor powder and solvent for injectable suspension before intramuscular deep injection.

Signifor suspension should only be prepared immediately before administration.

Signifor should only be administered by a healthcare professional with experience.