NEXPOVIO 20 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

NEXPOVIO 20 mg film-coated tablets

selinexor

This medicine is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start taking 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 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is NEXPOVIO and what is it used for

NEXPOVIO contains the active substance selinexor. Selinexor is a cancer medicine that has been shown to be an XPO1 inhibitor. It blocks the action of a substance called XPO1 that transports proteins from the nucleus of the cell to its cytoplasm. Some cellular proteins need to be in the nucleus to function properly.

By blocking the action of XPO1, selinexor prevents certain proteins from leaving the nucleus, and thus interferes with the continued growth of cancer cells and causes their death.

What is NEXPOVIO used for

NEXPOVIO is used to treat adult patients with multiple myeloma that has come back after treatment.

NEXPOVIO is used

• in combination with two other medicines called bortezomib and dexamethasone in people who have received at least one previous treatment.

Or

• in combination with dexamethasone in patients who have received at least four types of treatment for myeloma and whose disease cannot be controlled with previous medicines used to treat multiple myeloma.

Multiple myeloma is a cancer that affects a type of blood cell called plasma cells. Plasma cells normally produce proteins to fight infections. People with multiple myeloma have cancerous plasma cells, also called myeloma cells, which can damage bones and kidneys and increase the risk of infection. Treatment with NEXPOVIO destroys myeloma cells and reduces the symptoms of the disease.

2. What you need to know before you take NEXPOVIO

Do not take NEXPOVIO

If you are allergic to selinexor or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor or pharmacist before you start taking NEXPOVIO and during treatment if:

• you have or have had bleeding problems;
• you have recently had an infection or get an infection;
• you have nausea, vomiting, or diarrhea;
• you lose your appetite or lose weight;
• you suffer from confusion and dizziness;
• you experience a reduction in the amount of sodium in the blood (hyponatremia);
• you have a new or worsening cataract.

Your doctor will examine you and closely monitor you during treatment. Before you start taking NEXPOVIO and during treatment, you will have blood tests to check that you have enough blood cells.

Children and adolescents

NEXPOVIO should not be given to children and adolescents under 18 years of age.

Other medicines and NEXPOVIO

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy

A pregnancy test is recommended before treatment with NEXPOVIO in women who can become pregnant.

Do not use NEXPOVIO during pregnancy, as it may harm the fetus. Women who become pregnant while taking NEXPOVIO should stop treatment immediately and inform their doctor.

Breast-feeding

It is not known whether selinexor or its metabolites are excreted in breast milk and may harm breast-fed children, so breast-feeding should be avoided during treatment with NEXPOVIO and for 1 week after the last dose.

Fertility

NEXPOVIO may affect the fertility of men and women.

Contraception

Women who can become pregnant should use effective contraceptives during treatment and for at least 1 week after the last dose.

Men are advised to use effective contraceptive measures or avoid sexual intercourse with women who can become pregnant during treatment and for at least 1 week after the last dose.

Driving and using machines

NEXPOVIO may cause fatigue, confusion, and dizziness. Do not drive or use machines if you have a reaction of this type while being treated with this medicine.

NEXPOVIO contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 20 mg tablet; this is essentially "sodium-free".

3. How to take NEXPOVIO

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is:

• when taken with bortezomib and dexamethasone: 100 mg (5 tablets) once a day, on day 1 of each week, or as indicated by your doctor.
• when taken with dexamethasone: 80 mg (4 tablets) once a day, on days 1 and 3 of each week, or as indicated by your doctor.

If side effects occur, your doctor may adjust the dose.

It is important to follow exactly the administration instructions of this medicine given by your doctor to avoid dosing errors.

Method of administration

Swallow the NEXPOVIO tablets whole with a full glass of water, with or without food. Do not chew, crush, divide, or break the tablets to avoid the risk of the active substance causing skin irritation.

Duration of use

Your doctor will tell you how long the treatment will last, depending on your response to treatment and any side effects that may occur.

If you take more NEXPOVIO than you should

Call your doctor or go to the emergency department of the nearest hospital immediately. Bring the package leaflet and any remaining tablets with you.

If you forget to take NEXPOVIO

Do not take a double dose to make up for forgotten doses. Also, do not take an extra dose if you vomit after taking NEXPOVIO. Take the next dose as scheduled.

If you stop taking NEXPOVIO

Do not stop taking or change the dose of NEXPOVIO without your doctor's approval. However, if you become pregnant while taking NEXPOVIO, you should stop treatment immediately and inform your doctor.

If you have any other questions about 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.

Tell your doctor or nurse immediately if you notice any of the following side effects.

NEXPOVIO may cause the following serious side effects:

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

• reduction in the number of platelets in the blood

Your doctor will perform blood tests before you start taking NEXPOVIO and when necessary during and after treatment. These tests will be more frequent during the first two months of treatment to monitor your platelet count in the blood. Your doctor may stop treatment or adjust the dose based on your platelet count. Tell your doctor immediately if you have signs of a low platelet count, such as:

• easy bruising or excessive bruising,
• skin changes that appear as a rash of purple spots,
• prolonged bleeding due to cuts,
• bleeding from the gums or nose,
• blood in the urine or stool.

• reduction in the number of red and white blood cells, including neutrophils and lymphocytes. Your doctor will perform blood tests to monitor your red and white blood cell counts before you start taking NEXPOVIO and when necessary during and after treatment. These tests will be more frequent during the first two months of treatment. Your doctor may stop treatment or adjust the dose based on your blood cell counts or treat you with other medicines to increase these counts. Tell your doctor immediately if you have signs of low neutrophil count, such as fever.
• fatigue

Tell your doctor if you experience new or worsening fatigue. Your doctor may adjust the dose if fatigue persists or worsens.

• nausea, vomiting, diarrhea

Tell your doctor immediately if you develop nausea, vomiting, or diarrhea. Your doctor may adjust the dose or interrupt treatment, depending on the severity of the symptoms. Your doctor may also prescribe medicines to take before or during treatment with NEXPOVIO to prevent and treat nausea, vomiting, or diarrhea.

• weight and/or appetite loss

Your doctor will weigh you before you start taking NEXPOVIO and when necessary during and after treatment. The frequency will be higher during the first two months of treatment. Tell your doctor if you lose your appetite and if you lose weight. Your doctor may adjust the dose if your appetite and weight decrease and/or prescribe medicines to increase your appetite. Take in adequate amounts of fluids and calories throughout treatment.

• reduction in sodium levels

Your doctor will perform blood tests to check your sodium levels before you start taking NEXPOVIO and when necessary during and after treatment. These tests will be more frequent during the first two months of treatment. Your doctor may adjust the dose and/or prescribe salt tablets or fluids based on your sodium level.

• confusional state and dizziness

Tell your doctor if you experience confusion. Avoid situations where dizziness or confusion may be a problem, and do not take any other medicine that may cause dizziness or confusion without talking to your doctor. If you experience confusion or dizziness, do not drive or operate heavy machinery until you have recovered. Your doctor may adjust the dose to reduce these symptoms.

• cataract

Tell your doctor if you experience symptoms of cataract, such as double vision, sensitivity to light, or glare. If you notice changes in your vision, your doctor will refer you to an eye specialist (an ophthalmologist) for an eye exam, and surgery may be necessary to remove the cataract and restore vision.

Tell your doctor or nurse immediately if you notice any of the following side effects.

Other possible side effects are:

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

• Pneumonia.
• Upper respiratory tract infection.
• Bronchitis.
• Viral infection of the nose and throat (nasopharyngitis).
• Nerve damage in the hands and feet that can cause tingling and numbness (peripheral neuropathy).
• Nosebleeds.
• Headache (cephalea).
• Dehydration.
• Increased blood sugar levels.
• Decreased potassium levels.
• Loss of sleep (insomnia).
• Decreased sense of taste.
• Blurred vision.
• Shortness of breath.
• Cough.
• Abdominal pain.
• Constipation.
• Lack of energy.
• Fever.

Common(may affect more than 1 in 100 people)

• Bacterial infection in the blood.
• Normally, the body releases chemicals into the bloodstream to fight an infection; when the body's response to these chemicals is unbalanced, changes occur that can damage several organs and systems (sepsis).
• Decreased neutrophil count with fever.
• Decreased phosphate levels.
• Increased potassium levels.
• Decreased calcium levels.
• Decreased magnesium levels.
• Mental confusion (hallucination).
• Increased amylase and lipase levels.
• Increased uric acid levels.
• Confused thinking (delirium).
• Fainting (syncope).
• Increased heart rate (tachycardia).
• Difficulty seeing.
• Lack of taste.
• Taste disorder.
• Balance disorder.
• Cognitive disorder.
• Attention disorder.
• Memory impairment.
• Low blood pressure (hypotension).
• Spinning sensation (vertigo).
• Indigestion, dry mouth, abdominal discomfort.
• Gas or bloating (abdominal distension).
• Itching of the skin.
• Muscle spasms.
• Kidney problems.
• General deterioration of physical condition, gait disturbance, malaise, chills.
• Increased levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase).
• Falls.
• Memory impairment, including amnesia.
• Increased levels of a muscle enzyme called creatine.
• Hair loss.
• Night sweats, including excessive sweating.
• Lower respiratory tract infection.
• Bruising.

Uncommon(may affect up to 1 in 100 people):

• Rapid breakdown of tumor cells that could be life-threatening and cause symptoms such as muscle cramps, muscle weakness, confusion, vision loss or changes, and shortness of breath (tumor lysis syndrome).
• Brain inflammation that could cause confusion, headache (cephalea), seizures (encephalopathy).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, 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 NEXPOVIO

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, inner carton, and outer carton after "EXP". The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

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. Packaging Contents and Additional Information

NEXPOVIO Composition

• The active ingredient is selinexor. Each film-coated tablet contains 20 mg of selinexor.
• The other components are microcrystalline cellulose, sodium croscarmellose, povidone K30, sodium lauryl sulfate, colloidal silicon dioxide, magnesium stearate. The ingredients of the tablet coating are talc, partially hydrolyzed polyvinyl alcohol, glycerol monostearate, polysorbate 80, titanium dioxide, macrogol, aluminum indigo lake, and aluminum brilliant blue FCF lake. See section 2 "NEXPOVIO contains sodium".

Product Appearance and Packaging Contents

The NEXPOVIO film-coated tablets are blue, round, and engraved with "K20" on one side.

Each outer carton contains four child-resistant inner containers. Each inner container contains a plastic blister with 2, 3, 4, 5, or 8 tablets, which is equivalent to a total of 8, 12, 16, 20, or 32 tablets.

Marketing Authorization Holder

Stemline Therapeutics B.V.

Basisweg 10,

1043 AP Amsterdam

Netherlands

Manufacturer(s)

Stemline Therapeutics B.V.

Basisweg 10,

1043 AP Amsterdam

Netherlands

Berlin-Chemie AG

Glienicker Weg 125

12489 Berlin

Germany

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet: MM/YYYY.

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.