risdiplam: package leaflet

7.
1 Package Leaflet (not shown)
8.
1 Instructions for Constitution (not shown)
9.
1 Instructions for Use (not shown)
Figure A
Important information about Evrysdi

Avoid inhaling Evrysdi powder.

Use gloves.

Do not use if the powder expiry date has passed. The powder expiration date is printed on the bottle label.

Do not dispense the constituted solution if the solution’s Discard After date exceeds the original powder expiration date.

Avoid getting contact with the medicine on your skin. If the medicine gets on your skin, wash the area with soap and water.

Do not use the medicine if any of the supplies are damaged or missing.

Use Purified Water or Water for Injection to constitute the medicine.

Do not add oral syringes other than the ones provided in the carton.

How to store Evrysdi

Store the powder (unconstituted medicine) at room temperature (< 25°C) and keep it in the carton with the bottle tightly closed in order to protect from moisture.

Store the solution (constituted medicine) in a refrigerator (2 to 8°C) and keep it in the carton upright.

Keep the oral solution in the original bottle and always keep the bottle in an upright position with the cap tightly closed.
Constitution
Figure B
Step 1
Gently tap the bottom of the bottle to loosen the powder (See Figure B).
Figure C
Step 2
Remove the cap by pushing it down and then twisting to the left (counter-clockwise) (See Figure C). Do not throw away the cap.
Figure D
Step 3
Carefully pour 79 mL of Purified Water or Water for Injection into the medicine bottle (See Figure D).

Figure E
Step 4
Hold the medicine bottle on a table with one hand.
Insert the press-in bottle adaptor into the opening by pushing it down with the other hand. Ensure it is completely pressed against the bottle lip (See Figure E).
Figure F
Step 5
Put the cap back on the bottle. Turn the cap to the right (clockwise) to close the bottle.
Ensure it is completely closed and then shake well for 15 seconds (See Figure F).
Wait for 10 minutes. You should have obtained a clear solution.
Afterwards, shake well again for another
15 seconds.
Figure G
Step 6
Calculate the Discard After date as 64 days after constitution (Note: the day of constitution is counted as day 0. For example, if constitution is on the 1st of April, the Discard After date will be the 4th of June).
Write the Discard After date of the solution on the bottle label (See Figure G) and carton.
Put the bottle back in its original carton, with syringes (in pouches), Package Leaflet and Instructions For Use booklet.
Store the carton in the refrigerator (2 to 8°C).

Evrysdi contains the active substance risdiplam. It is part of a group of medicines known as ‘pre- mRNA splicing modifiers’.
Evrysdi is used to treat spinal muscular atrophy (SMA) in adults and children.

SMA is an illness that runs in families – a genetic illness.

It is caused by a shortage of a protein called ‘survival motor neuron’ (SMN) in the body.
If you do not have enough SMN protein, you lose motor neurons. Motor neurons are nerve cells that control muscles.

This leads to muscle weakness and wasting.

This can make everyday movements difficult, such as head and neck control, sitting, crawling and walking.

The muscles used for breathing and swallowing may also become weaker.
How Evrysdi works
Evrysdi works by helping the body produce more SMN protein.

This means you lose fewer motor neurons – this may improve how well muscles work in people with SMA.
In infants with SMA Type 1, Evrysdi may:
 increase how long they live
 reduce the need for a ventilator to help with breathing
 help them be able to keep being fed by mouth.

In children (toddlers to adolescents) and adults with SMA Type 2 and 3, Evrysdi may:
 stop muscle control getting worse
 improve muscle control.

Do not take Evrysdi:
 if you are allergic to risdiplam or any of the other ingredients of this medicine (listed in section 6).
If you are not sure, talk to your doctor, pharmacist, or nurse before you take Evrysdi.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you take Evrysdi.
Treatment with Evrysdi may harm your unborn baby or may affect male fertility. See “Pregnancy”, “Contraception”, and “Male fertility” for more information.
Other medicines and Evrysdi
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken or might take any other medicines in the future.
In particular tell your doctor, pharmacist, or nurse if you are taking or have ever taken any of the following medicines:
 metformin – a medicine used to treat type 2 diabetes
 medicines for the treatment of SMA
Pregnancy
Before you start treatment with this medicine, your doctor should do a pregnancy test. This is because Evrysdi may harm your unborn baby.

Do not take this medicine if you are pregnant.

Do not become pregnant:
- during your treatment with Evrysdi and
- for one month after you stop taking Evrysdi.
If you do become pregnant during your treatment, tell your doctor straight away. You and your doctor will decide what is best for you and your unborn baby.
Contraception
For women
You must use a highly effective method of birth control:
 while taking this medicine and
 for one month after you stop taking this medicine.
Talk to your doctor about highly effective methods of birth control that you and your partner can use.
For men
If your partner is a woman who can have children, she must not become pregnant.
Use condoms:
 while taking this medicine and

 for 4 months after you stop taking this medicine.
Talk to your doctor about highly effective methods of birth control that you and your partner can use.
Breast-feeding
Do not breast-feed while taking this medicine. This medicine may pass into breast milk and may harm your baby.
Talk to your doctor about whether you should stop breast-feeding or if you should stop taking Evrysdi.
Male fertility
Evrysdi may reduce male fertility during treatment and for up to 4 months after your last dose.

If you are planning to have a child, ask your doctor for advice.

Do not donate sperm during your treatment and for 4 months after your last dose of this medicine.
Driving and using machines
This medicine is unlikely to affect your ability to drive and use machines.
Evrysdi contains sodium
Evrysdi contains a small amount of sodium (salt) - there is less than 1 mmol (23 mg) sodium. This means it is essentially ‘sodium-free’ and can be used by people on a sodium-restricted diet.

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
You have received blister packs of Evrysdi as film-coated tablets, referred to as a ‘tablet’ in this leaflet. This medicine is also available as an oral solution. Your doctor will have helped you choose the right one for you.
How much Evrysdi to take
Evrysdi tablets are used in patients who are 2 years of age or older and weigh 20 kg or more.
For Evrysdi tablets, the dose is 5 mg (one tablet) once daily.
You must take your daily dose as instructed by your doctor.

Do not change the dose without speaking with your doctor.
When and how to take Evrysdi
Read the ‘Instructions for Use’ at the end of this leaflet. Follow the instructions carefully. It shows you exactly how to make and take Evrysdi as a mixture.

Take Evrysdi:
 once a day, at around the same time - this will help you remember when to take your medicine  with or without food.
There are two ways your doctor may tell you to take Evrysdi tablets:


Take Evrysdi by mouth. Swallow each tablet whole with some water.
- Do not cut, crush or chew the tablets.
Or

Take Evrysdi by mouth or through a feeding tube that is 8 French or higher after dispersing it in a small amount of room temperature water.
- Do not mix Evrysdi with any liquids other than water.
- Take Evrysdi tablet straight away after mixing fully with water. If you do not take it within 10 minutes of adding water, throw the mixture away and make a new dose.
- Do not expose the tablet mixture prepared from the Evrysdi tablet to sunlight.
- Do not get Evrysdi tablet mixture on your skin or in your eyes. If Evrysdi gets on your skin, wash the area with soap and water. If Evrysdi gets in your eyes, rinse your eyes with water.
How long to take Evrysdi for
Your doctor will tell you how long you need to take Evrysdi. Do not stop treatment with Evrysdi unless your doctor tells you.
If you take more Evrysdi than you should
If you take more Evrysdi than you should, talk to a doctor or go to hospital straight away.

Take the medicine pack and this leaflet with you.
If you forget to take Evrysdi or vomit after a dose
If you forget to take a dose:

If it is less than 6 hours after you normally take Evrysdi - take the missed dose as soon as you remember.

If it is over 6 hours from when you normally take Evrysdi - skip the missed dose and then take your next dose at the usual time. Do not take a double dose to make up for a forgotten dose.
If you are sick (vomit) after taking Evrysdi:

Do not take an extra dose. Instead, take the next dose at the usual time the next day.
If you spill Evrysdi
If you spill Evrysdi tablet mixture, dry the area with a dry paper towel and then clean the area with soap and water. Throw away the paper towel in the rubbish and wash your hands well with soap and water.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common: may affect more than 1 in 10 people
 diarrhoea
 rash
 headache
 fever
Common: may affect up to 1 in 10 people
 feeling sick (nausea)
 mouth sores

 bladder infection
 joint pain
Not known: it is not known how often these happen
 inflamed small blood vessels mainly in the skin (cutaneous vasculitis)
Reporting of side effects
If you get any side effects, talk to your doctor or 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.


Keep this medicine out of the sight and reach of children.

This medicinal product does not require any special temperature storage conditions.

Store in the original package in order to protect from moisture.
Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP.
The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Evrysdi contains

The active substance in the tablet is risdiplam.

Each tablet contains 5 mg risdiplam.

The other ingredients are tartaric acid (E 334), mannitol (E 421), microcrystalline cellulose, silica, colloidal anhydrous (E 551), crospovidone, strawberry flavour [natural flavouring substance(s), flavouring preparation(s), maize maltodextrin, modified waxy maize starch (E1450)] and sodium stearyl fumarate, polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350 (E 1521), talc (E 553b) and yellow iron oxide (E 172).
What Evrysdi looks like and contents of the pack

Evrysdi tablets are pale yellow film-coated tablets, round and curved, with EVR debossed on one side.

Evrysdi is supplied in packs containing 28 x 1 tablets. There are 4 aluminium perforated unit- dose blisters with 7 tablets each.
- The blisters strips are each marked with abbreviated names of the day as a reminder to take a daily dose:
Mon. Tue. Wed. Thu. Fri. Sat. Sun

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien,
Luxembourg/Luxemburg
N.V. Roche S.A.
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11
Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831
България
Рош България ЕООД
Тел: +359 2 474 5444
Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799
Česká republika
Roche s. r. o.
Tel: +420 - 2 20382111
Magyarország
Roche (Magyarország) Kft.
Tel: +36 1 279 4500
Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99
Nederland
Roche Nederland B.V.
Tel: +31 (0) 348 438000
Deutschland
Roche Pharma AG
Tel: +49 (0) 7624 140
Norge
Roche Norge AS
Tlf: +47 - 22 78 90 00
Eesti
Roche Eesti OÜ
Tel: + 372 - 6 177 380
Österreich
Roche Austria GmbH
Tel: +43 (0) 1 27739
Ελλάδα, Κύπρος
Roche (Hellas) A.E.
Ελλάδα
Τηλ: +30 210 61 66 100
Polska
Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88
España
Roche Farma S.A.
Tel: +34 - 91 324 81 00
Portugal
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00
France
Roche
Tél: +33 (0) 1 47 61 40 00
România
Roche România S.R.L.
Tel: +40 21 206 47 01

Hrvatska
Roche d.o.o.
Tel: +385 1 4722 333
Slovenija
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00
Ireland, Malta
Roche Products (Ireland) Ltd.
Ireland/L-Irlanda
Tel: +353 (0) 1 469 0700
Slovenská republika
Roche Slovensko, s.r.o.
Tel: +421 - 2 52638201
Ísland
Roche Pharmaceuticals A/S c/o Icepharma hf
Sími: +354 540 8000
Suomi/Finland
Roche Oy
Puh/Tel: +358 (0) 10 554 500
Italia
Roche S.p.A.
Tel: +39 - 039 2471
Sverige
Roche AB
Tel: +46 (0) 8 726 1200
This leaflet was last revised in
Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu.

Instructions for Use – Administration
Evrysdi film-coated tablets
This Instructions for Use contains information on how to prepare and take Evrysdi.

The information in this Instructions for Use is for taking or giving this medicine – but here we just say ‘take’.
Before you start
Read this Instructions for Use before taking Evrysdi film-coated tablets for the first time and each time you get a refill. There may be new information.
Evrysdi film-coated tablets can be swallowed whole or mixed with a small amount of room temperature water and taken by mouth or given through a feeding tube [i.e., a nasogastric (NG tube) or gastrostomy (G tube) tube].
Important Information

Your doctor, pharmacist, or nurse will show you how to prepare and take Evrysdi tablets.
Always take Evrysdi tablets exactly as your healthcare provider tells you.

Do not take or give this medicine until you have been shown how to properly prepare and take Evrysdi.

Wash your hands before and after preparing or taking Evrysdi.

Check the expiry date and check the product for damage before use. Do not use if expired or damaged.

Do not get the Evrysdi tablet mixture on your skin or in your eyes. If the Evrysdi tablet mixture gets on your skin, wash the area with soap and water. If the tablet mixture gets in your eyes, rinse your eyes with water.

Keep the Evrysdi tablet mixture out of sunlight.

If you spill the Evrysdi tablet mixture, dry the area with a dry paper towel and then clean with soap and water. Throw away the paper towel in the rubbish and wash your hands with soap and water.
How to take Evrysdi tablets

If you are taking Evrysdi tablets, the daily dose is 1 tablet.

Take the tablet whole with water or as a liquid by mixing 1 tablet in at least 1 teaspoon (5 ml) of room temperature water.

Do not chew, cut, or crush the tablet.

Do not mix Evrysdi with any liquids other than water.

Do not take Evrysdi tablet mixture if it has been more than 10 minutes since adding water to the tablet. Throw the mixture away according to your local requirements and make a new dose.

Do not take an extra dose if you are sick (vomit) at any time after taking Evrysdi.

Get ready to take an Evrysdi tablet
Step 1. Wash your hands. (Figure A).
Figure A
Step 2. Take out 1 Evrysdi tablet from the blister
(Figure B).
Figure B
Option A: Swallow the Evrysdi tablet whole
Step A1
Swallow the tablet whole with some water.
Do not chew, cut, or crush the tablet
Do not swallow with any liquids other than water.
Step A2
Wash your hands with soap and water.

Option B: Take Evrysdi tablet mixed in water
What is needed to mix Evrysdi with water:
●1 Evrysdi tablet
●a small, clean empty cup
●at least 1 teaspoon (5 ml) of room temperature water for mixing
●at least 1 tablespoon (15 ml) of water for rinsing
Step B1
Put at least 1 teaspoon (5 ml) of water in a cup – and add
1 tablet.
●
Do not use any liquids other than water,
●
Keep the mixture out of sunlight.
Figure C
Step B2
Gently swirl the cup until it is fully mixed - this can take up to
3 minutes. Some particles may remain after swirling (Figure C).
To take by mouth see Step C1
To take by feeding tube see Step D1
Take Evrysdi by mouth
Step C1
Drink immediately after mixing fully.
Drink within 10 minutes of adding water to the tablet
(Figure D).
Figure D
Step C2
Refill the cup with at least 1 tablespoon (15 ml) of water and swirl to get any medicine left in the cup (Figure E).
Figure E
Step C3
Drink immediately (Figure F).
Go to Step E1 for clean-up instructions
Figure F

Administration through a gastrostomy or nasogastric tube
You can take or give the mixture through a gastrostomy or nasogastric tube placed by a healthcare professional.
Check the manufacturer’s instructions for the size and dimensions of the enteral tube. Ensure the tube size is at least 8 French or higher to prevent clogging.
You will need:
 a small clean empty cup

1 syringe (volume between 5 mL and 20 mL) compatible with the feeding tube (oral or enteral). Ask your pharmacist if you need help selecting the correct size.
The syringe and medicine cup are not included in the package and can be obtained from the pharmacy.
The syringe and cup may be reused if the manufacturer’s instructions allow.
Step D1
Administer immediately after mixing fully.
Administer within 10 minutes of adding water to the tablet.
Place the syringe tip into the cup and slowly pull up the plunger to draw up all the mixture (Figure G).
Figure G
Step D2
Place the syringe tip into the gastrostomy/nasogastric tube.
Slowly press the plunger all the way down to give the full dose of
Evrysdi (Figure H1 and H2).
Figure H1
Figure H2
Step D3
Check that there is no medicine left in the syringe (Figure I).
Figure I

Step D4
Refill the cup with at least 1 tablespoon (15 ml) of water and swirl to get any medicine left in the cup (Figure J).
Place the syringe into the cup and pull up the plunger to draw up all the mixture.
Figure J
Step D5
Flush the gastrostomy or nasogastric tube with the mixture
(Figure K1 and K2).
Go to Step E1 for clean-up instructions.
Figure K1
Figure K2
After administering
Step E1
Wash your hands with soap and water.
Check with your pharmacist if the syringe and/or cup provided by the pharmacy is intended for single use only or can be re-used multiple times.

Syringes or cups intended for single use must be disposed after use.

Syringes or cups for multiple use must be cleaned immediately after use. Ask your pharmacist for the manufacturer’s instructions.
Discard disposable items according to your local requirements.
Storing Evrysdi

This medicinal product does not require any special temperature storage conditions.

Store in the original package in order to protect from moisture.

Keep Evrysdi and all medicines out of the sight and reach of children.