SIGNIFOR 0.9 mg INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Signifor0.3mg solution for injection

Signifor 0.6mgsolution for injection

Signifor 0.9mgsolution for injection

pasireotide

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Signifor and what is it used for
2. What you need to know before you use Signifor
3. How to use Signifor
4. Possible side effects
5. Storage of Signifor
6. Contents of the pack and other information

1. What is Signifor and what is it used for

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

Cushing's disease is caused by an increase in the size of the pituitary gland (a gland located at the base of the brain) called a pituitary adenoma. This causes the body to produce too much 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 questions about how Signifor works or why you have been prescribed this medicine, ask your doctor.

2. What you need to know before you use Signifor

Do not use Signifor:

• if you are allergic to pasireotide or any of the other ingredients of this medicine (listed in section 6).
• if you have severe liver problems.

Warnings and precautions

Tell your doctor before you start using Signifor if you have or have had:

• problems with blood sugar levels, either too high (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, severe chest pain (usually felt as pressure, heaviness, tightness, or pain in the chest);
• a heart rhythm disorder, such as an irregular heartbeat or an abnormal electrical signal called "prolonged QT interval" or "QT prolongation";
• low levels of potassium or magnesium in the blood;
• gallstones.

During your treatment with Signifor

• Signifor controls the overproduction of cortisol. The control may be too strong and may present signs or symptoms associated with a lack of cortisol, such as extreme weakness, tiredness, weight loss, nausea, vomiting, or low blood pressure. If this happens to you, tell your doctor immediately.
• Signifor may cause an increase in blood sugar levels. Your doctor may check your blood sugar levels and start treatment or adjust your antidiabetic medication.
• Signifor may slow your heart rate. Your doctor may check your heart rate using a machine that measures the electrical activity of the heart (an "ECG" or electrocardiogram). If you are using a medicine 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 medicine.

Children and adolescents

Do not give this medicine to children and adolescents under 18 years of age because there is no data available for this age group.

Other medicines and Signifor

Signifor may affect the way other medicines work. If you are using other medicines at the same time as Signifor (including non-prescription medicines), your doctor may need to monitor your heart more closely or change the dose of Signifor or the other medicines. Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. In particular, tell your doctor if you are using:

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

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

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

It is particularly important to tell your doctor if you are using:

• cyclosporin (used in organ transplantation to reduce the activity of the immune system);
• medicines to treat high or low blood sugar levels, such as:

• insulin;
• metformin, liraglutide, vildagliptin, nateglinide (antidiabetic medicines).

Pregnancy, breast-feeding, and fertility

Ask your doctor or pharmacist for advice before taking any medicine.

• Do not use Signifor during pregnancy unless clearly necessary. If you are pregnant or think you may be pregnant, tell your doctor, who will decide with you whether you can use Signifor during your pregnancy.
• Do not breast-feed while using Signifor. It is not known whether Signifor passes into breast milk.
• If you are a sexually active woman, you should use an effective method of contraception during treatment. Ask your doctor about the need for contraception before using this medicine.

Driving and using machines

Signifor may have a minor effect on your ability to drive and use machines, as some of the side effects you may experience while using Signifor, such as dizziness, headache, and tiredness, may reduce your ability to drive and use machines safely.

Important information about some of the ingredients of Signifor

Signifor contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to use Signifor

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, ask your doctor or pharmacist again. This medicine comes in an ampoule, which is a small glass container.

How much Signifor to use

The recommended dose is one ampoule of Signifor 0.6 mg twice a day. Using Signifor at the same time each day will help you remember when to use your medicine. After starting treatment, your doctor may decide to increase the dose to one ampoule of Signifor 0.9 mg twice a day.

If side effects occur, your doctor may temporarily reduce the dose by 0.3 mg per injection.

If you have liver disease before starting treatment with Signifor, your doctor may decide to start treatment with a dose of one ampoule of Signifor 0.3 mg twice a day.

Ampoules of Signifor of different strengths (0.3 mg, 0.6 mg, and 0.9 mg) are available to administer the specific dose prescribed by your doctor.

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

How to use Signifor

Your doctor or nurse will teach you how to inject Signifor yourself. You should also read the instructions at the end of this leaflet. If you have any questions, contact your doctor, pharmacist, or nurse.

Signifor must be administered subcutaneously. This means it is injected with a short needle into the fatty tissue just under the skin. The thighs and abdomen are suitable areas for subcutaneous injection. Using a different site from the previous injection for each injection will help avoid pain and skin irritation. You should also avoid injecting into areas that are painful or where the skin is irritated.

Do not use Signifor if you notice that the solution is not clear or contains particles. The solution should be free of particles, clear, and colorless.

For how long to use Signifor

You should continue to use Signifor for as long as your doctor tells you.

If you use more Signifor than you should

If you have accidentally used more Signifor than your doctor prescribed, contact your doctor, pharmacist, or nurse immediately.

If you forget to use Signifor

Do not inject a double dose of Signifor to make up for forgotten doses. If you forget to inject a dose of Signifor, simply inject the next dose at the scheduled time.

If you stop using Signifor

If you stop using Signifor, your cortisol levels may increase again and your symptoms may return. Therefore, do not stop using Signifor unless your doctor tells you to.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

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

• Change in blood sugar levels. You may notice excessive thirst, urination, increased appetite with weight loss, tiredness, nausea, vomiting, abdominal pain.
• Gallstones or associated complications. You may experience fever, chills, yellowing of the skin/eyes, sudden back pain or pain in the right side of the abdomen.
• Extreme tiredness.

Common (may affect up to 1 in 10 people)

• Low cortisol levels. You may experience extreme weakness, tiredness, weight loss, nausea, vomiting, and low blood pressure.
• Slow heart rate.
• Low blood pressure. You may experience dizziness, mild headache, and dizziness or fainting when standing up.
• Problems with bile flow (cholestasis). You may experience yellowing of the skin, dark urine, pale stools, and itching.
• Inflammation of the gallbladder (cholecystitis).

Other side effects of Signifor may include:

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

• Diarrhea
• Nausea
• Stomach pain
• Pain at the injection site

Common (may affect up to 1 in 10 people)

• Prolonged QT interval (an abnormal electrical signal in the heart that can be seen on tests)
• Loss of appetite
• Vomiting
• Headache
• Dizziness
• Hair loss
• Itching (pruritus)
• Muscle pain (myalgia)
• Joint pain (arthralgia)
• Abnormal liver function test results
• Abnormal pancreatic function test results
• Abnormal blood coagulation properties

Uncommon (may affect up to 1 in 100 people)

• Low red blood cell count (anemia)

Frequency not known (cannot be estimated from the available data)

• High levels of 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 experience fruity breath odor, breathing problems, and confusion.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Signifor

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the ampoule label and carton after "EXP"/"CAD". The expiry date is the last day of the month stated.
• Store in the original package to protect from light.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Signifor

• The active ingredient is pasireotide.

Signifor 0.3 mg: A 1 ml solution ampoule contains 0.3 mg of pasireotide (as pasireotide diaspartate).

Signifor 0.6 mg: A 1 ml solution ampoule contains 0.6 mg of pasireotide (as pasireotide diaspartate).

Signifor 0.9 mg: A 1 ml solution ampoule contains 0.9 mg of pasireotide (as pasireotide diaspartate).

• The other components are mannitol, tartaric acid, sodium hydroxide, and water for injectable preparations.

Appearance of Signifor and Container Content

Signifor injectable solution is a clear and colorless solution in an ampoule. Each ampoule contains 1 ml of injectable solution.

Signifor is available in packs containing 6 ampoules or in multipacks containing 18 (3 packs of 6), 30 (5 packs of 6), or 60 (10 packs of 6) ampoules.

It is possible that, in your country, only some doses and some pack sizes are marketed.

Marketing Authorization Holder

Recordati Rare Diseases

Immeuble Le Wilson

70 avenue du Général de Gaulle

92800 Puteaux

France

Manufacturer

Novartis Pharma GmbH

Roonstrasse 25

D-90429 Nürnberg

Germany

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 medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

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

INSTRUCTIONS FOR USE OF SIGNIFOR INJECTABLE SOLUTION

This medicinal product comes in an ampoule, i.e., a small glass container. Signifor must be administered using disposable syringes and needles for injection.

Your doctor or nurse will have given you instructions on how to use Signifor ampoules. However, before using the ampoule, read the following information carefully. If you are unsure about how to administer the injection yourself or if you have any doubts, contact your doctor or nurse for help.

The injection can be prepared using either two different needles for withdrawing and injecting the solution or a short fine needle for injection for these two steps. Based on local clinical practice, your doctor or nurse will inform you about which method to use. Please follow their instructions.

Store the Signifor ampoules according to the storage conditions indicated on the carton.

Important Safety Information

Caution: Keep the ampoules out of the reach of children.

What You Need

To inject yourself, you will need:

1. A Signifor ampoule
2. An alcohol swab or similar
3. A sterile syringe
4. A sterile long thick needle with a blunt tip for withdrawing the solution (your doctor or nurse will inform you if you need it)
5. A sterile short fine needle
6. A needle container or another rigid closed container for disposal

Injection Site

The injection site is the place on your body where the injection will be administered. Signifor is administered subcutaneously. This means it is injected using a short needle into the fatty tissue just under the skin. The thighs and abdomen are suitable areas for subcutaneous injection. Using a different site from the previous injection will avoid pain and irritation. You should also avoid injecting into areas that are painful or where the skin is irritated.

Preparation

When you are ready to administer the injection yourself, carefully follow the following steps:

• Wash your hands thoroughly with water and soap.
• Use disposable syringes and needles each time you administer an injection. Use syringes and needles only once. Nevershare needles or syringes.
• Take the ampoule out of the carton.

• Inspect the ampoule. DO NOT USE IT if it is broken or if the liquid appears cloudy or contains particles. In all these cases, return the complete package to the pharmacy.

To reduce local discomfort, it is recommended that the solution be kept at room temperature before administration.

The ampoules should be opened just before administration, and any unused portion should be discarded.

Check the Expiration Date and Dose

Check the expiration date on the ampoule label (after "EXP") and check that the ampoule contains the dose prescribed by your doctor.

DO NOT USE IT if the medicinal product has expired or if the dose is not correct. In both cases, return the complete package to the pharmacy.

How to Inject Signifor