Nexpovio 20 mg film-coated tablets

Patient Information Leaflet

Introduction

Package Leaflet: Information for the Patient

NEXPOVIO 20 mg film-coated tablets

selinexor

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is provided at the end of section 4.

Read this entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What NEXPOVIO is and what it is used for

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

By blocking XPO1 activity, selinexor prevents certain proteins from leaving the nucleus, thereby interfering with the continuous growth of cancer cells and causing their death.

What NEXPOVIO is used for

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

NEXPOVIO is used

• in combination with two other medicines called bortezomib and dexamethasone in patients who have received at least one prior therapy.

Or

• in combination with dexamethasone in patients who have received at least four prior therapies for multiple myeloma and whose disease is refractory to previous treatments used for multiple myeloma.

Multiple myeloma is a cancer affecting a type of blood cell called plasma cells. Plasma cells normally produce proteins to fight infections. In patients with multiple myeloma, cancerous plasma cells—also called myeloma cells—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 starting NEXPOVIO

Do not take NEXPOVIO

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

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with NEXPOVIO and during treatment if:

• you have or have had bleeding problems;
• you have recently had an infection or develop an infection;
• you have nausea, vomiting, or diarrhea;
• you lose your appetite or lose weight;
• you experience confusion or dizziness;
• you develop low sodium levels in the blood (hyponatremia);
• you develop a new cataract or worsening of an existing cataract.

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

Children and adolescents

NEXPOVIO must 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 need to take any other medicines.

Pregnancy

A pregnancy test is recommended before starting treatment with NEXPOVIO in women of childbearing potential.

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

Breastfeeding

It is unknown whether selinexor or its metabolites are excreted in human milk and may cause harm to breastfed infants. Therefore, breastfeeding is not recommended during treatment with NEXPOVIO and for 1 week after the last dose.

Fertility

NEXPOVIO may affect fertility in both men and women.

Contraception

Women of childbearing potential must use effective contraception 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 of childbearing potential 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 operate machinery if you experience such reactions while being treated with this medicine.

NEXPOVIO contains sodium

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

3. How to take NEXPOVIO

Follow exactly the administration instructions for this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Recommended dose:

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

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

It is important that you follow exactly the administration instructions for this medicine as given by your doctor to avoid dosing errors.

Method of administration

Swallow the NEXPOVIO tablets whole with a full glass of water, either with food or between meals. Do not chew, crush, split, or break the tablets to avoid the risk of skin irritation from the active substance.

Duration of use

Your doctor will determine the duration of treatment based on your response to therapy and any side effects that may occur.

If you take more NEXPOVIO than you should

Call your doctor or go immediately to the nearest hospital emergency department. Take the pack of NEXPOVIO tablets with you.

If you forget to take NEXPOVIO

Do not take a double dose to make up for missed 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 approval from your doctor. However, if you become pregnant while taking NEXPOVIO, you must stop treatment immediately and inform your doctor.

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

4. Possible adverse effects

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

Immediately inform your doctor or nurse 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 as needed during and after treatment. These tests will be more frequent during the first two months of treatment to monitor your platelet counts. Your doctor may stop treatment or adjust the dose based on your platelet counts. Immediately inform your doctor if you have signs of reduced platelet count, such as:

• bruises that appear easily or excessively,

• skin changes manifesting as a rash of small red-purple spots,

• prolonged bleeding from cuts,

• bleeding from gums or nose,

• blood in urine or stools.

• 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 as needed during and after treatment. These tests will be more frequent during the first two months of treatment. Your doctor may stop or adjust the dose depending on your blood cell counts or treat you with other medicines to increase these counts. Immediately inform your doctor if you have signs of low neutrophils, such as fever.

• fatigue

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

• nausea, vomiting, diarrhoea

Immediately inform your doctor if you develop nausea, vomiting, or diarrhoea. Your doctor may adjust the dose or interrupt treatment depending on the severity of symptoms. Additionally, your doctor may prescribe medications to take before or during treatment with NEXPOVIO to prevent and treat nausea, vomiting, or diarrhoea.

• decreased weight and/or appetite

Your doctor will weigh you before you start taking NEXPOVIO and as needed during and after treatment. This will be done more frequently during the first two months of treatment. Inform your doctor if you lose your appetite or lose weight. Your doctor may adjust your dose if your appetite and weight decrease and/or prescribe medications to increase appetite. Maintain adequate fluid and calorie intake throughout treatment.

• reduction in sodium levels

Your doctor will perform blood tests to check your sodium levels before you start taking NEXPOVIO and as needed 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 depending on your sodium level.

• confusional state and dizziness

Inform your doctor if you experience confusion. Avoid situations where dizziness or a confusional state could be problematic, and do not take any other medication that may cause dizziness or confusion without first 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

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

Immediately inform your doctor or nurse if you notice any of the side effects listed below.

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 may cause tingling and numbness (peripheral neuropathy).
• Nosebleed.
• Headache (cephalalgia).
• Dehydration.
• Increased blood sugar level.
• Decreased potassium level.
• Insomnia (sleep loss).
• Impaired sense of taste.
• Blurred vision.
• Shortness of breath.
• Cough.
• Abdominal pain.
• Constipation.
• Loss 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 infection; when the body's response to these chemicals is unbalanced, changes are triggered that may damage various organs and systems (sepsis).
• Reduction in neutrophil count accompanied by fever.
• Decreased phosphate level.
• Increased potassium level.
• Decreased calcium level.
• Decreased magnesium level.
• Mental confusion (hallucination).
• Increased amylase and lipase levels.
• Increased uric acid level.
• Confused thinking (delirium).
• Fainting (syncope).
• Increased heart rate (tachycardia).
• Difficulty seeing.
• Loss of taste.
• Taste disturbance.
• Balance disorder.
• Cognitive disorder.
• Attention disturbance.
• Memory impairment.
• Low blood pressure (hypotension).
• Spinning sensation (vertigo).
• Indigestion, dry mouth, abdominal discomfort.
• Flatulence or bloating (abdominal distension).
• Itching of the skin.
• Muscle spasm.
• Kidney problems.
• General physical deterioration, gait disturbance, malaise, chills.
• Increased liver enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase).
• Fall.
• Memory impairment, including amnesia.
• Increased level 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 tumour cells that could be life-threatening and causes symptoms such as muscle cramps, muscle weakness, confusion, vision loss or disturbances, and shortness of breath (tumour lysis syndrome).
• Brain inflammation that could cause confusion, headache (cephalalgia), seizures (encephalopathy).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the blister, the inner carton, and the outer carton, following "EXP". The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Package contents and other information

Composition of NEXPOVIO

• The active substance 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 tablet coating ingredients are talc, partially hydrolyzed polyvinyl alcohol, glyceryl monostearate, polysorbate 80, titanium dioxide, macrogol, indigo carmine aluminium lake and brilliant blue FCP aluminium lake. See section 2 “NEXPOVIO contains sodium”.

Appearance of the product and contents of the pack

NEXPOVIO film-coated tablets are blue, round and marked "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, resulting in a total of 8, 12, 16, 20 or 32 tablets.

Marketing Authorization Holder

Stemline Therapeutics B.V.

Basisweg 10,

1043 AP Amsterdam

The Netherlands

Manufacturer(s)

Stemline Therapeutics B.V.

Basisweg 10,

1043 AP Amsterdam

The Netherlands

Berlin-Chemie AG

Glienicker Weg 125

12489 Berlin

Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: MM/YYYY.

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