Product Information for the Patient

Isturisa 1 mg Film-Coated Tablets

Isturisa 5 mg Film-Coated Tablets

Isturisa 10 mg Film-Coated Tablets

osilodrostat

Read this entire product information carefully before starting to take this medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should 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 or pharmacist, even if they are not listed in this product information. See section 4.

What is Isturisa

Isturisa is a medication that contains the active ingredient osilodrostat.

What is Isturisa used for

Isturisa is used to treat endogenous Cushing's syndrome in adults, a disease in which the body produces too much of a hormone called cortisol. Excess cortisol can cause a variety of symptoms such as weight gain (especially around the waist), a moon-shaped face, easy bruising, irregular periods, excessive hair on the body and face, and generally a feeling of weakness, fatigue, or discomfort.

How Isturisa works

Isturisa blocks the main enzyme that produces cortisol in the adrenal glands. The result is a decrease in the overproduction of cortisol and an improvement in the symptoms of endogenous Cushing's syndrome.

Do not take Isturisa:

• if you are allergic to osilodrostat or any of the other ingredients of this medication (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before taking Isturisa.

If you are in any of the following situations, inform your doctor before taking Isturisa:

• if you have a heart condition or a heart rhythm disorder, such as irregular heartbeat, including a condition called prolonged QT syndrome (prolongation of the QT interval).
• if you have liver disease; your doctor may need to change the dose of Isturisa.

Contact your doctor immediately if you have two or more of the following symptoms during your treatment with Isturisa. This may indicate that you have adrenal insufficiency (low cortisol levels):

• weakness
• dizziness
• fatigue
• loss of appetite
• nausea
• vomiting

These symptoms may continue for months after stopping treatment with Isturisa. Contact your doctor as you may need additional treatment and/or monitoring.

Pre-treatment and during treatment controls

Your doctor will perform blood and/or urine tests before starting treatment and regularly during treatment. This is to detect any possible changes in magnesium, calcium, and potassium levels and also to measure cortisol levels. Depending on the results, your doctor may change the dose you take.

This medication may have an unwanted effect (called QT prolongation) on heart function. Your doctor will therefore also monitor this effect by performing an electrocardiogram (ECG) before starting treatment and during treatment.

If your Cushing's syndrome is due to a benign tumor (called adenoma) in the pituitary gland, your doctor may consider stopping treatment if the adenoma scan shows that the adenoma has expanded into adjacent areas.

Children and adolescents

This medication is not recommended for patients under 18 years of age. This is due to the lack of data in these patients.

Other medications and Isturisa

Inform your doctor if you are taking, have taken recently, or may need to take any other medication. It is especially important to mention any of the following medications:

• medications that may have an unwanted effect (called QT prolongation) on heart function. These include medications used for abnormal heart rhythm such as quinidine, sotalol, and amiodarone; allergy medications (antihistamines); antidepressants such as amitriptyline and medications for mental disorders (antipsychotics); antibiotics, including the following types: macrolides, fluoroquinolones, or imidazoles; and other medications for Cushing's disease (pasireotide, ketoconazole)
• theophylline (used to treat respiratory problems) or tizanidine (used to treat muscle pain and muscle cramps).

Pregnancy and breastfeeding

This medication should not be used during pregnancy and breastfeeding unless your doctor has indicated otherwise. If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

Contraception

Women who may become pregnant should use an effective contraceptive method during treatment and for at least one week after the last dose. Consult your doctor about the need for contraception before starting treatment with Isturisa.

Driving and operating machinery

Dizziness and fatigue may occur during treatment with Isturisa. Do not drive or operate machinery if you have these symptoms.

Isturisa contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor.

If in doubt, consult your doctor or pharmacist again.

The usual starting dose is two 1 mg tablets twice a day (approximately every 12 hours). Patients of Asian origin and patients with liver disease may need a lower starting dose (one 1 mg tablet twice a day).

After starting treatment, your doctor may change the dose. This will depend on how you respond to treatment. The maximum recommended dose is 30 mg twice a day.

Isturisa tablets are taken orally and can be taken with or without food.

If you take more Isturisa than you should

If you have taken more Isturisa than you should and do not feel well (for example, you feel weak, dizzy, tired, nauseous, or have vomiting), or if another person accidentally takes your medication, contact a doctor or hospital immediately. You may need medical treatment.

If you forget to take Isturisa

Do not take a double dose to make up for the missed doses. Instead, wait until the next scheduled dose and take it at the usual time.

If you interrupt treatment with Isturisa

Do not stop taking Isturisa unless your doctor tells you to. If you stop taking Isturisa, your symptoms may return.

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

Some side effects can be serious.Please pay special attention to the following:

• Inform your doctor immediately if you experience a heart or heart rhythm alteration, such as rapid and irregular heartbeats, even at rest, palpitations, dizziness, or fainting (this may be a sign of a condition called QT prolongation, a side effect that can affect up to 1 in 10 people).
• Inform your doctor immediately if you have two or more of the following symptoms: weakness, dizziness, fatigue, loss of appetite, nausea, vomiting. This may indicate that you have adrenal insufficiency (low cortisol levels), a side effect that can affect more than 1 in 10 patients. Adrenal insufficiency occurs when Isturisa decreases cortisol levels too much. It is more likely to occur during periods of increased stress. Your doctor will correct this situation by using a hormone medication or adjusting the Isturisa dose.

Very common side effects(can affect more than 1 in 10 people):

• low cortisol levels (adrenal hypofunction)
• vomiting
• nausea
• diarrhea

• abdominal pain
• fatigue
• fluid accumulation, leading to swelling (edema), especially in the ankles
• blood test abnormalities (increased testosterone levels, increased adrenocorticotropic hormone levels, also known as ACTH, low potassium levels)
• loss of appetite
• dizziness
• rapid heart rate (tachycardia)
• muscle pain (myalgia)
• joint pain (arthralgia)
• headache
• skin rash
• low blood pressure (hypotension)
• excessive hair growth on the face or body (hirsutism)
• acne

Common side effects(can affect up to 1 in 10 people):

• general feeling of being unwell (malaise)
• abnormal liver function test results
• fainting (syncope)
• abnormal heart rhythm that affects heart rate.

Reporting side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on 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 and on the blister after CAD/EXP. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Isturisa

• The active ingredient is osilodrostat. Each film-coated tablet contains 1 mg of osilodrostat, 5 mg of osilodrostat, or 10 mg of osilodrostat.
• The other components are:
• • In the tablet core: microcrystalline cellulose, mannitol, sodium croscarmellose (see section 2 "Isturisa contains sodium"), magnesium stearate, anhydrous colloidal silica.
  • In the coating: hypromellose, titanium dioxide (E171), iron oxides (E172, see below), macrogol, and talc.
  • • Isturisa 1 mg film-coated tablets contain yellow iron oxide and red iron oxide.

• Isturisa 5 mg film-coated tablets contain yellow iron oxide.
• Isturisa 10 mg film-coated tablets contain yellow iron oxide, red iron oxide, and black iron oxide.

Appearance of Isturisa and contents of the pack

Isturisa is available in packs containing 60 film-coated tablets.

The 1 mg tablets are light yellow, round, uncoated, and have a "1" engraved on one side. The approximate diameter is 6.1 mm.

The 5 mg tablets are yellow, round, uncoated, and have a "5" engraved on one side. The approximate diameter is 7.1 mm.

The 10 mg tablets are light orange-brown, round, uncoated, and have a "10" engraved on one side. The approximate diameter is 9.1 mm.

Marketing Authorisation Holder

Recordati Rare Diseases

Tour Hekla

52 avenue du Général de Gaulle

92800 Puteaux

France

Responsible Person

Millmount Healthcare Ltd

Block 7, City North

Business Campus, Stamullen,

Co. Meath, K32 YD60,

Ireland

Recordati Rare Diseases

Tour Hekla

52 avenue du Général de Gaulle

92800 Puteaux

France

Recordati Rare Diseases

Eco River Parc

30 rue des Peupliers

92000 Nanterre

France

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of the summary of product characteristics:12/2024

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:https://www.ema.europa.eu