Signifor 20 mg powder and solvent for suspension for injection

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, nurse or pharmacist.
• 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, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

• 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.

Talk to your doctor before using Signifor if you currently have or have ever had:

• problems with your blood sugar levels, whether too high (as in hyperglycaemia/diabetes) or too low (hypoglycaemia);
• heart problems such as a recent heart attack, congestive heart failure (a type of heart disease where the heart cannot pump enough blood around the body) or sudden and oppressive chest pain (usually felt as pressure, heaviness, tightening, squeezing or aching across the chest);
• a heart rhythm disorder, such as an irregular heartbeat or an abnormal electrical signal called “prolongation of the QT interval”, or “QT prolongation”;
• low levels of potassium or magnesium in your blood;
• gallstones;
• or if you are taking anticoagulants (medicines used to reduce the clotting ability of the blood), your doctor will monitor your coagulation parameters and may adjust your anticoagulant dose.

During your treatment with Signifor:

• Signifor may cause your blood sugar to increase. Your doctor may want to monitor your blood sugar and start treatment with or adjust your antidiabetic medicine.
• Signifor controls over-production of cortisol. The control may be too strong and you may experience 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, tell your doctor immediately.
• Signifor may lower your heart rate. Your doctor may wish to monitor your heart rate using a machine that measures electrical activity of the heart (an “ECG”, or electrocardiogram). If you are using medicine to treat a heart condition, your doctor may also need to adjust its dosage.
• your doctor may also wish to check your gallbladder, liver enzymes and pituitary hormones periodically, since these might all be affected by this medicine.

Do not give this medicine to children and adolescents below 18 years old because no data are available in this age group.

Signifor may affect the way some other medicines work. If you are using other medicines at the same time as Signifor (including medicines obtained without a prescription), your doctor may need to monitor your heart more carefully 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. Especially, tell your doctor if you are using:

• medicines used in organ transplantation to reduce the activity of the immune system (ciclosporin);
• medicines to treat blood sugar levels that are too high (as in diabetes) or too low (hypoglycaemia) such as:
  • insulin
  • metformin, liraglutide, vildagliptin, nateglinide (antidiabetic medicines);
• medicines to treat irregular heartbeat, such as medicines containing disopyramide, procainamide, quinidine, sotalol, dofetilide, ibutilide, amiodarone or dronedarone;
• medicines to treat bacterial infections (by mouth: clarithromycin, moxifloxacin; via 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 in the prevention or treatment of 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 your body.

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

• You should not use Signifor during pregnancy unless clearly necessary. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
• If you are breast-feeding, ask your doctor for advice before taking this medicine, as 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 taking this medicine.

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

Signifor contains less than 1 mmol sodium (23 mg) per dose, which means it is essentially “sodium-free”.

Acromegaly

The recommended starting dose of Signifor in acromegaly is 40 mg every 4 weeks. After you have started treatment, your doctor may reassess your dose. This may involve measuring the levels of growth hormone or other hormones in your blood. Depending on the results and how you are feeling, the dose of Signifor given in each injection may need to be reduced or increased. The dose should not exceed 60 mg. If you have liver disease before you start Signifor treatment for acromegaly, your doctor may want to start your treatment with a dose of 20 mg.

Cushing’s disease

The usual starting dose of Signifor in Cushing’s disease is 10 mg every 4 weeks. After you have started treatment, your doctor may reassess your dose. This may involve measuring the levels of cortisol in your blood or urine. Depending on the results and how you are feeling, the dose of Signifor given in each injection may need to be reduced or increased. The dose should not exceed 40 mg.

Your doctor will check regularly how you respond to the treatment with Signifor and determine which dose is best for you.

Your doctor or nurse will inject Signifor. If you have any questions, contact your doctor, nurse or pharmacist.

Signifor is intended for intramuscular use. This means that it is injected through a needle into the muscles of your buttocks.

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

If you interrupt your treatment with Signifor your symptoms may come back. Therefore, do not stop using Signifor unless your doctor tells you to.

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

• High level of sugar in the blood. You may experience excessive thirst, high urine output, increased appetite with weight loss, tiredness, nausea, vomiting, abdominal pain
• Gallstones or associated complications. You may experience fever, chills, yellowing of skin/eyes, sudden back pain or pain in the right side of your abdomen.

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 beat.
• Prolonged QT interval (an abnormal electrical signal in your heart that can be seen in tests).
• Problems with bile flow (cholestasis). You may experience yellowing of the skin, dark urine, pale stools, and itching.
• Inflammation of the gallbladder (cholecystitis).

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

• Diarrhoea
• Nausea
• Abdominal pain
• Fatigue

Common (may affect up to 1 in 10 people)

• Tiredness, fatigue, pale skin (signs of low level of red blood cells)
• Loss of appetite
• Headache
• Bloating
• Vomiting
• Dizziness
• Pain, discomfort, pruritis and swelling at the injection site
• Change in liver function test results
• Abnormal blood test results (sign of high level of creatine phosphokinase, glycosylated haemoglobin, lipase in the blood)
• Hair loss

Uncommon (may affect up to 1 in 100 people)

• Change in pancreatic function blood test results (amylase)
• Abnormal blood coagulation properties

Not known (frequency cannot be estimated from the available data)

• Increased levels of ketone bodies (a group of substances produced in the liver) in your urine or blood (diabetic ketoacidosis) as a complication of an increased level of sugar in your blood. You may experience fruity scented breath, trouble breathing and confusion.
• Oily or fatty stools
• Discoloured stools

If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gouv.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is pasireotide.
  Signifor 10 mg: each vial contains 10 mg pasireotide (as pasireotide pamoate).
  Signifor 20 mg: each vial contains 20 mg pasireotide (as pasireotide pamoate).
  Signifor 30 mg: each vial contains 30 mg pasireotide (as pasireotide pamoate).
  Signifor 40 mg: each vial contains 40 mg pasireotide (as pasireotide pamoate).
  Signifor 60 mg: each vial contains 60 mg pasireotide (as pasireotide pamoate).
• The other ingredients 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: carmellose sodium, mannitol, poloxamer 188, water for injections.

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

Signifor 10 mg is available in unit packs containing one vial of powder with 10 mg pasireotide and one pre filled syringe with 2 ml solvent.

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

Signifor 30 mg is available in unit packs containing one vial of powder with 30 mg pasireotide and one pre filled syringe with 2 ml solvent.

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

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

Each unit pack contains the vial and pre-filled syringe in a sealed blister tray with one vial adapter and one safety-engineered needle for injection.

Signifor 40 mg and Signifor 60 mg are also available in multipacks containing 3 intermediate packs.

Not all strengths or pack sizes may be marketed in your country.