NINLARO 3 mg HARD CAPSULES

2. What you need to know before you take NINLARO

Do not take NINLARO:

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

If you are unsure if this applies to you, talk to your doctor, pharmacist, or nurse before taking NINLARO.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to take NINLARO or during treatment if:

• you have a history of bleeding disorders
• you have persistent nausea, vomiting, or diarrhea
• you have a history of nerve problems, including numbness or tingling
• you have a history of swelling
• you have a persistent skin rash or a severe skin rash with peeling of the skin and sores in the mouth (Stevens-Johnson syndrome or toxic epidermal necrolysis, see section 4)
• you have or have had liver or kidney problems, as the dose may need to be adjusted
• you have or have had problems with small blood vessels, known as thrombotic microangiopathy or thrombocytopenic purpura. Tell your doctor if you develop fatigue, fever, bruising, bleeding, decreased urine output, swelling, confusion, vision loss, and seizures.

Your doctor will examine you and monitor you closely during treatment. Before starting to take NINLARO and during treatment, you will have blood tests to check that you have enough blood cells.

Children and adolescents

The use of NINLARO is not recommended in children and adolescents under 18 years of age.

Using NINLARO with other medicines

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. This includes any medicines obtained without a prescription, such as vitamins or herbal medicines. Other medicines may affect the way NINLARO works. In particular, tell your doctor, pharmacist, or nurse if you are taking any of the following medicines: carbamazepine, phenytoin, rifampicin, and St. John's Wort (Hypericum perforatum). These medicines should be avoided as they may reduce the effectiveness of NINLARO.

Pregnancy and breastfeeding

NINLARO is not recommended during pregnancy as it may harm the fetus. Breastfeeding should be discontinued while taking NINLARO.

Avoid becoming pregnant or breastfeeding while being treated with NINLARO. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, talk to your doctor or pharmacist before using this medicine.

If you are a woman of childbearing age or a man with reproductive potential, you must use effective contraception during treatment and for 90 days after treatment. Women using a hormonal contraceptive method should also use a barrier method. Tell your doctor immediately if you or your partner becomes pregnant while you are being treated with NINLARO.

Since NINLARO is given in combination with lenalidomide, you must follow the lenalidomide pregnancy prevention program because lenalidomide can be harmful to the fetus.

See the lenalidomide and dexamethasone package leaflets for more information on pregnancy and breastfeeding.

Driving and using machines

NINLARO may affect your ability to drive or use machines. You may feel tired and dizzy while taking NINLARO. Do not drive or use machines if you have these side effects.

3. How to take NINLARO

NINLARO must be prescribed by a doctor with experience in treating multiple myeloma. Always follow exactly the administration instructions given by your doctor or pharmacist.

NINLARO is used with lenalidomide (a medicine that affects the way your immune system works) and dexamethasone (an anti-inflammatory medicine).

NINLARO, lenalidomide, and dexamethasone are taken in 4-week cycles of treatment.

NINLARO is taken once a week (on the same day of the week) during the first 3 weeks of the cycle.

The recommended dose is one 4 mg capsule taken orally.

The recommended dose of lenalidomide is 25 mg taken every day during the first 3 weeks of a cycle. The recommended dose of dexamethasone is 40 mg taken once a week on the same day in all 4 weeks of the cycle.

Read the package leaflets of these other medicines for more information on their use and effects.

If you have liver or kidney problems, your doctor may prescribe NINLARO 3 mg capsules. If you experience side effects, your doctor may prescribe NINLARO 3 mg or 2.3 mg capsules. Your doctor may also adjust the doses of the other medicines.

How and when to take NINLARO

• Take NINLARO at least 1 hour before or at least 2 hours after a meal.
• Swallow the capsule whole with water. Do not break, open, or chew the capsule.
• Avoid contact between the capsule contents and your skin. If the powder accidentally comes into contact with your skin, wash the skin carefully with water and soap. If the capsule is broken, collect the powder, avoiding raising dust in the air.

If you take more NINLARO than you should

An accidental overdose may cause serious side effects. If you take more NINLARO than you should, talk to your doctor or go to the hospital immediately. Take the medicine package with you.

Duration of treatment with NINLARO

You should continue treatment until your doctor tells you to stop.

If you forget to take NINLARO

If you forget or are late taking a dose, take the dose if it is more than 3 days or 72 hours until the next scheduled dose. Do not take the missed dose if it is less than 3 days or 72 hours until the next scheduled dose.

If you vomit after taking a dose, do not take an extra dose. Take the next dose when it is scheduled.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Stop using ixazomib and seek medical help immediately if you experience any of the following symptoms:

• red, target-like, or circular patches on the torso, often with blisters in the center, peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis, which can affect up to 1 in 1,000 people).

Tell your doctor immediately if you experience any of the following serious side effects that can affect more than 1 in 10 people:

• low platelet count (thrombocytopenia), which can increase the risk of nosebleeds and easy bruising
• nausea, vomiting, and diarrhea
• numbness, tingling, or burning sensation in hands or feet (peripheral neuropathy)
• swelling in legs or feet (peripheral edema)
• skin rashes with itching in some areas of the body or all over the body
• cough, chest pain or inflammation, or nasal congestion (bronchitis)

Additionally, tell your doctor immediately if you experience any of the following rare side effects that can affect up to 1 in 1,000 people:

• severe skin rashes in the form of red to purple spots (Sweet's syndrome)
• muscle weakness, loss of sensation in toes or feet, or loss of mobility in legs (transverse myelitis)
• vision changes, mental status changes, or seizures (reversible posterior encephalopathy syndrome)
• rapid destruction of cancer cells, which can cause dizziness, decreased urine output, confusion, vomiting, nausea, swelling, shortness of breath, or heart rhythm changes (tumor lysis syndrome)
• a rare blood disorder caused by blood clots that can cause fatigue, fever, bruising, bleeding, decreased urine output, swelling, confusion, vision loss, and seizures (thrombotic microangiopathy, thrombocytopenic purpura)
• swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing, wheezing, chest tightness, or dizziness, itching, and hives (angioedema or anaphylactic reaction)

Other possible side effects

Tell your doctor or pharmacist if any of the following side effects become serious.

Very common: may affect more than 1 in 10 people

• constipation
• back pain
• cold symptoms (upper respiratory tract infection)
• feeling tired or weak (fatigue)
• low white blood cell count, called neutrophils (neutropenia), which can increase the risk of infection
• loss of appetite
• irregular heartbeat (arrhythmia)
• eye problems, such as blurred vision, dry eyes, and conjunctivitis

Common: may affect up to 1 in 10 people

• reactivation of the varicella virus (herpes) that can cause skin rash and pain (herpes zoster)
• low blood pressure (hypotension)
• shortness of breath or cough or wheezing (heart failure)
• yellowing of the eyes and skin (jaundice, which can be a sign of liver failure)
• low potassium levels in the blood (hypokalemia)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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 NINLARO

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 blister, carton, and packaging after EXP. The expiry date is the last day of the month shown.

Do not store above 30°C. Do not freeze.

Store in the original package to protect from moisture.

Do not remove the capsule until it is time to take a dose.

Do not use this medicine if you notice damage or signs of tampering.

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

NINLARO Composition

NINLARO 2.3 mg hard capsule:

• The active substance is ixazomib. Each capsule contains 2.3 mg of ixazomib (equivalent to 3.3 mg of ixazomib citrate).
• Other components are:

• In the capsule: microcrystalline cellulose, magnesium stearate, and talc.
• The capsule shell contains: gelatin, titanium dioxide (E171), and red iron oxide (E172).
• The printing ink contains: shellac, propylene glycol, potassium hydroxide, and black iron oxide (E172).

NINLARO 3 mg hard capsule:

• The active substance is ixazomib. Each capsule contains 3 mg of ixazomib (equivalent to 4.3 mg of ixazomib citrate).
• Other components are:

• In the capsule: microcrystalline cellulose, magnesium stearate, and talc.
• The capsule shell contains: gelatin, titanium dioxide (E171), and black iron oxide (E172).
• The printing ink contains: shellac, propylene glycol, potassium hydroxide, and black iron oxide (E172).

NINLARO 4 mg hard capsule:

• The active substance is ixazomib. Each capsule contains 4 mg of ixazomib (equivalent to 5.7 mg of ixazomib citrate).
• Other components are:

• In the capsule: microcrystalline cellulose, magnesium stearate, and talc.
• The capsule shell contains: gelatin, titanium dioxide (E171), yellow iron oxide (E172), and red iron oxide (E172).
• The printing ink contains: shellac, propylene glycol, potassium hydroxide, and black iron oxide (E172).

NINLARO Appearance and Container Content

NINLARO 2.3 mg hard capsule: light pink, size 4, marked with “Takeda” on the cap and “2.3 mg” on the body with black ink.

NINLARO 3 mg hard capsule: light gray, size 4, marked with “Takeda” on the cap and “3 mg” on the body with black ink.

NINLARO 4 mg hard capsule: light orange, size 3, marked with “Takeda” on the cap and “4 mg” on the body with black ink.

Each box contains 3 hard capsules (three individual boxes, each with a sealed blister pack inside a carton. Each blister pack contains one capsule).

Marketing Authorization Holder

Takeda Pharma A/S

Delta Park 45

2665 Vallensbaek Strand

Denmark

Manufacturer

Takeda Ireland Limited

Grange Castle Business Park

Nangor Road

Dublin 22

D22 XR57

Ireland

Takeda GmbH

Takeda (Werk Singen)

Robert Bosch Strasse 8

78224 Singen

Germany

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.