Evrysdi

Patient Information Leaflet

Evrysdi 0.75 mg/mL oral solution powder

risdiplam
Please read all of this leaflet carefully before taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you/for your child only. Do not give it to other people, even if their symptoms are the same as yours or your child's, because it may be harmful.
• If you or your child experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.
• Although this patient leaflet uses the term "you", the information provided applies to you, the caregiver, or your child.

Contents of this leaflet

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

1. What Evrysdi is and what it is used for

What Evrysdi is and what it is used for
Evrysdi contains the active substance risdiplam. It belongs to 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 inherited, genetic disease.
• It is caused by a deficiency of a protein called SMN (survival motor neuron) in the body.

The lack of SMN protein can lead to the loss of motor neurons. Motor neurons are nerve cells that control muscles.

• This condition causes muscle weakness and wasting.
• This can make everyday movements difficult, such as head and neck control, sitting, crawling, and walking.
• Muscles used for breathing and swallowing may also weaken.

How Evrysdi works
Evrysdi works by helping the body produce more SMN protein.

• This results in reduced loss of motor neurons and improved muscle function in people with SMA.

In infants with Type 1 SMA, Evrysdi may:

• increase life expectancy;
• reduce the need for artificial ventilation;
• preserve the ability to feed orally.

In children (from young children to adolescents) and adults with Type 2 and Type 3 SMA, Evrysdi may:

• stop the worsening of muscle control;
• improve muscle control.

2. What you need to know before taking Evrysdi

Do not take Evrysdi

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

If you have any doubts, talk to your doctor, pharmacist, or nurse before taking Evrysdi.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Evrysdi.
Treatment with Evrysdi may harm the unborn fetus 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 particular, inform 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 starting treatment with this medicine, your doctor will ask you to take a pregnancy test. This is because Evrysdi may have harmful effects on the fetus.

• Do not take this medicine if you are pregnant.
• You must avoid becoming pregnant:
  • during treatment with Evrysdi and
  • for one month after stopping treatment with Evrysdi.

If you become pregnant during treatment, inform your doctor immediately. You and your doctor will decide what is best for you and the fetus.
Contraception
Women
You must use a highly effective method of contraception:

• during treatment with this medicine and
• for one month after stopping treatment with this medicine.

Discuss with your doctor which highly effective contraceptive methods you and your partner can use.
Men
If your partner is of childbearing age, you must avoid any pregnancy.
Use a condom:

• during treatment with this medicine and
• for 4 months after stopping treatment with this medicine.

Discuss with your doctor which highly effective contraceptive methods you and your partner can use.
Breast-feeding
You must not breast-feed while taking this medicine, as this medicine may pass into breast milk and may harm the baby.
Discuss with your doctor whether you should stop breast-feeding or stop taking Evrysdi.
Male fertility
Evrysdi may reduce male fertility during treatment and for up to 4 months after the last dose.

• If you are planning to have a child, consult your doctor.
• It is important not to donate sperm during treatment and for 4 months after the last dose of this medicine.

Driving and using machines
It is unlikely that this medicine will affect your ability to drive or use machines.
Evrysdi contains sodium
Evrysdi contains a small amount of sodium (salt), less than 1 mmol (23 mg) of sodium. This means it is essentially “sodium-free” and can be used by people on a low-sodium diet.
Evrysdi oral solution powder contains 0.375 mg of sodium benzoate per mL. Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks of age).
Evrysdi contains isomalt
Evrysdi oral solution powder contains 2.97 mg of isomalt per mL. If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.

3. How to take Evrysdi

Take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
If you are taking Evrysdi powder for oral solution, you must take the medicine in liquid form
contained in a vial. Evrysdi is a liquid prepared by the pharmacist, referred to in this leaflet as “oral solution” or “medicinal product”. If the contents of the vial are in powder form, do not use it and contact your pharmacist.
Evrysdi is also available as a film-coated tablet. Your doctor will help you choose the formulation most suitable for you.
Dose of Evrysdi
Your doctor will determine the correct dose of Evrysdi based on the patient's age and weight.
You must take the daily dose as instructed by your doctor.

• Do not change the dose without first consulting your doctor.

When and how to take Evrysdi
The package includes the "Instructions for use", which will show you how to draw up the dose using the reusable oral syringe provided. You may take the medicine:

• by mouth, or
• through a feeding tube.

You must also read carefully and follow the instructions provided in the enclosed "Instructions for use", which contain information on how to take or administer Evrysdi.
Take Evrysdi:

• once daily, approximately at the same time each day; this will help you remember when to take the medicine;
• with or without food;
• immediately after preparing the oral syringe. If it is not taken within 5 minutes, the medicine in the oral syringe must be discarded and a new dose prepared.

Drink some water after taking the medicine. Do not mix the medicine with milk or infant formula.
If Evrysdi comes into contact with your skin, wash the area with water and soap.
Duration of treatment with Evrysdi
Your doctor will tell you how long you should take Evrysdi. Do not stop treatment with Evrysdi unless instructed to do so by your doctor.
If you take more Evrysdi than you should
If you take more Evrysdi than you should, contact your doctor immediately or go to hospital straight away.

• Take the medicine packaging and this leaflet with you.

If you forget to take Evrysdi or vomit after taking a dose
If you forget to take a dose:

• If less than 6 hours have passed since your usual dosing time, take the missed dose as soon as you remember.
• If more than 6 hours have passed since your usual dosing time, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. If you vomit after taking Evrysdi:
• Do not take an extra dose. Instead, take the next dose at the usual time the following day.

If you spill Evrysdi
If you spill this medicine, wipe up the area with a dry paper towel and then clean it with water and soap. Dispose of the paper towel in the waste and wash your hands thoroughly with water and soap.
If you have any questions about how to use this medicine, consult your doctor, pharmacist or nurse.

4. Possible side effects

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

Very common: may affect more than 1 in 10 people

• diarrhoea
• rash
• headache
• fever

Common: may affect up to 1 in 10 people

• nausea
• mouth ulcers
• bladder infection
• joint pain

Not known: frequency cannot be estimated from the available data

• inflammation of small blood vessels, mainly in the skin (cutaneous vasculitis)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system listed in Annex V.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Evrysdi

• Keep this medicine out of the sight and reach of children.
• Store the oral solution in the refrigerator (2 °C–8 °C). If necessary, the oral solution may be stored at room temperature (below 40 °C) for a total period not exceeding 120 hours (5 days). Return the oral solution to the refrigerator when it is no longer necessary to keep the bottle at room temperature.
• Monitor the total time the bottle remains outside the refrigerator (below 40 °C). As stated above, the cumulative time outside the refrigerator must not exceed 120 hours.
• If stored in the refrigerator at 2 °C–8 °C, the oral solution is stable for 64 days after preparation by the pharmacist. The pharmacist will write the expiry date on the label of the bottle and on the original carton after “Expiry date”. Do not use the solution after this “Expiry date”, or discard the medicine if the bottle has been stored at room temperature (below 40 °C) for a total time exceeding 120 hours (5 days).
• Discard the medicine if the bottle has been stored at any time at a temperature above 40 °C.
• Store the medicine in the original bottle to protect it from light.
• Keep the medicine bottle in an upright position with the cap tightly closed.
• Once the medicine has been withdrawn from the bottle using the oral syringe, use Evrysdi immediately. Do not store the Evrysdi solution in the syringe.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Evrysdi contains

• The active substance in the oral solution is risdiplam.
• Each mL of oral solution contains 0.75 mg of risdiplam.
• The other components are mannitol (E 421), isomalt (E 953), strawberry flavour [natural flavouring(s), flavouring preparation(s), corn maltodextrin, modified waxy corn starch (E1450)], tartaric acid (E 334), sodium benzoate (E 211), macrogol 6000 (E 1521), sucralose, ascorbic acid (E 300), disodium edetate dihydrate (see section 2 “Evrysdi contains sodium” and “Evrysdi contains isomalto”).

Description of the appearance of Evrysdi and package contents

• Evrysdi oral solution powder is supplied as an oral solution after preparation by the pharmacist.
• The oral solution is yellowish-green to yellow in colour, strawberry-flavoured, with a volume of 80 mL.
• Each pack contains 1 vial, 1 press-in adapter for the vial, and reusable amber-coloured graduated oral syringes (two 1 mL, two 6 mL, and one 12 mL) to help you draw up the correct dose.

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

België/Belgique/Belgien, Latvija, Luxembourg/Luxemburg
Roche Latvija SIA
N.V. Roche S.A.
Tel: +371 - 6 7039831
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11

България, Lietuva
Рош България ЕООД
UAB “Roche Lietuva”
Тел: +359 2 474 5444
Tel: +370 5 2546799

Česká republika, Magyarország
Roche s. r. o.
Roche (Magyarország) Kft.
Tel: +420 - 2 20382111
Tel: +36 1 279 4500

Danmark, Nederland
Roche Pharmaceuticals A/S
Roche Nederland B.V.
Tlf: +45 - 36 39 99 99
Tel: +31 (0) 348 438050

Deutschland, Norge
Roche Pharma AG
Roche Norge AS
Tel: +49 (0) 7624 140
Tlf: +47 - 22 78 90 00

Eesti, Österreich
Roche Eesti OÜ
Roche Austria GmbH
Tel: +372 - 6 177 380
Tel: +43 (0) 1 27739

Ελλάδα, Κύπρος, Polska
Roche (Hellas) A.E.
Roche Polska Sp.z o.o.
Ελλάδα
Τηλ: +30 210 61 66 100
Tel: +48 - 22 345 18 88

España, Portugal
Roche Farma S.A.
Roche Farmacêutica Química, Lda
Tel: +34 - 91 324 81 00
Tel: +351 - 21 425 70 00

France, România
Roche
Tél: +33 (0) 1 47 61 40 00
Roche România S.R.L.
Tel: +40 21 206 47 01

Hrvatska, Slovenija
Roche d.o.o.
Roche farmacevtska družba d.o.o.
Tel: +385 1 4722 333
Tel: +386 - 1 360 26 00

Ireland, Malta, Slovenská republika
Roche Products (Ireland) Ltd.
Roche Slovensko, s.r.o.
Ireland/L-Irlanda
Tel: +353 (0) 1 469 0700
Tel: +421 - 2 52638201

Ísland, Suomi/Finland
Roche Pharmaceuticals A/S
c/o Icepharma hf
Sími: +354 540 8000
Roche Oy
Puh/Tel: +358 (0) 10 554 500

Italia, Sverige
Roche S.p.A.
Roche AB
Tel: +39 - 039 2471
Tel: +46 (0) 8 726 1200

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

Instructions for use - Administration

Evrysdi 0.75 mg/mL oral solution powder

risdiplam
Be sure to read and understand the Instructions for Use before starting to use Evrysdi.
These instructions show how to prepare and administer Evrysdi using an oral syringe, a gastrostomy tube (G-tube), or a nasogastric tube (NG-tube).
If you have any questions about how to use Evrysdi, consult your doctor or pharmacist.
Evrysdi must be supplied as a liquid contained in a vial. The oral solution of Evrysdi is prepared by a pharmacist. Do not use the medicine if the vial contents are in powder form; contact your pharmacist.

Important information about Evrysdi

• Always use the reusable oral syringes provided in the package to measure the daily dose.
• See “How to select the correct oral syringe for the Evrysdi dose”.
• Ask your pharmacist if you have any doubts about how to select the correct oral syringe from the package or how to measure the daily dose.
• Contact your doctor or pharmacist if the oral syringe(s) are lost or damaged. You will receive advice on how to continue taking the medicine.
• If the vial adapter is not in the vial, do not use Evrysdi and contact your pharmacist.
• The oral solution can be stored at room temperature (below 40 °C) for no more than 120 hours (5 days) in total. Monitor the total time outside the refrigerator (at temperatures below 40 °C).
• Do not use Evrysdi after the expiry date printed on the vial label, or if you or the caregiver have stored the vial at room temperature (below 40 °C) for longer than 120 hours (5 days) in total. If the expiry date is not shown on the vial label, ask your pharmacist for the expiry date.
• Discard the medicine if the vial has been stored at a temperature above 40 °C for any period of time.
• Do not mix Evrysdi with milk or formula milk.
• Do not use Evrysdi if the vial or oral syringes are damaged.
• Avoid contact of Evrysdi with the skin. If contact occurs, wash the area with soap and water.
• In case of spillage of Evrysdi, wipe up the spill with a dry paper towel and then clean the area with soap and water. Dispose of the paper towel in the waste and wash hands thoroughly with soap and water.
• If there is not enough Evrysdi in the vial to deliver the required dose, dispose of the vial containing the remaining Evrysdi solution and used oral syringes according to local regulations. Use a new vial of Evrysdi to administer the full dose. Do not mix the Evrysdi solution from the new vial with the one currently in use.

Each EVRYSDI package contains (Figure A):

1. 1 vial of Evrysdi with adapter and cap
2. 1 oral syringe of 12 mL (in pouch)
3. 2 oral syringes of 6 mL (in pouches)
4. 2 oral syringes of 1 mL (in pouches)
5. 1 Instructions for Use (not shown)
6. 1 Package Leaflet (not shown) Figure A

How to store Evrysdi
See section 5 “How to store Evrysdi” of the Package Leaflet for complete information.

A) Drawing up the dose volume
How to select the correct oral syringe for the Evrysdi dose

If the daily dose of Evrysdi is between 0.3 mL and 1 mL, use a 1 mL oral syringe (yellow label).
If the daily dose of Evrysdi is between 1 mL and 6 mL, use a 6 mL oral syringe (grey label).
If the daily dose of Evrysdi is greater than 6 mL, use a 12 mL oral syringe (brown label).
Ask your doctor or pharmacist how to round your or your child’s daily dose to the nearest syringe marking.

How to draw up the Evrysdi dose

Step A1
Remove the cap by pushing it downward and then rotating it to the left (counterclockwise) (Figure B).
Do not discard the cap.
Figure B

Step A2
Push the oral syringe plunger fully down to remove air from the oral syringe (Figure C).
Figure C

Step A3
Holding the vial upright, insert the tip of the syringe into the vial adapter (Figure D).
Figure D

Step A4
Carefully invert the vial with the syringe tip securely inserted into the vial adapter (Figure E).
Figure E

Step A5
Slowly pull the plunger outward to draw up the Evrysdi dose. The top of the black plunger stopper should align with the mL mark on the oral syringe corresponding to the daily dose (Figure F).
After drawing up the correct dose, hold the plunger steady to prevent it from moving.
Figure F

Step A6
Continue to hold the plunger steady to prevent movement. Leave the oral syringe in the vial adapter, rotate the vial upright, place it on a flat surface, and gently pull the oral syringe upward to remove it from the vial adapter (Figure G).
Figure G

Step A7
Hold the oral syringe with the tip pointing upward. Check the medicine in the syringe.
If large air bubbles are present in the oral syringe (Figure H) or if an incorrect dose of Evrysdi has been drawn, firmly reinsert the syringe tip into the vial adapter. Push the plunger fully down so that the medicine flows back into the vial, and repeat steps A4 to A7.
Take or administer Evrysdi immediately after drawing it into the oral syringe.
Figure H
If not taken within 5 minutes, discard the medicine in the oral syringe and draw a new dose.

Step A8
Replace the cap on the vial. Rotate the cap to the right (clockwise) to close the vial tightly (Figure I). Do not remove the adapter from the vial.
Figure I

If you are taking the Evrysdi dose orally, follow the instructions in section “B) How to take an Evrysdi dose by mouth”.
If you are administering the Evrysdi dose through a gastrostomy tube (G-tube), follow the instructions in section “C) How to administer an Evrysdi dose through a gastrostomy tube (G-tube)”.
If you are administering the Evrysdi dose through a nasogastric tube (NG-tube), follow the instructions in section “D) How to administer an Evrysdi dose through a nasogastric tube (NG-tube)”.

The oral syringes supplied with Evrysdi are specifically designed to be compatible with the ENFit enteral feeding system. If your feeding tube is not ENFit-compatible, you may need an ENFit transition connector to attach the Evrysdi syringe to the G-tube or NG-tube.

B) How to take a dose of Evrysdi orally

Sit upright when taking a dose of Evrysdi orally.

Step B1
Place the oral syringe into the mouth with the tip
along the cheek.
Slowly push the plunger all the way down to
administer the full dose of Evrysdi
(Figure J).
Administering Evrysdi directly into the
back of the throat or too
quickly may cause choking.
Figure J

Step B2
Check that no medicine remains in the oral syringe (Figure K).
Figure K

Step B3
Drink some water immediately after taking the
dose of Evrysdi (Figure L).
See section E for instructions on how to
clean the syringe.
Figure L

C) How to administer a dose of Evrysdi through a gastrostomy tube

If Evrysdi is administered through a gastrostomy tube, ask your doctor or nurse to demonstrate how to check the gastrostomy tube before administering Evrysdi.

Step C1
Insert the tip of the oral syringe into the gastrostomy tube. Slowly push the plunger down all the way to administer the full dose of Evrysdi (Figure M).
Figure M

Step C2
Check that no medicine remains in the oral syringe (Figure N).
Figure N

Step C3
Flush the gastrostomy tube with 10–20 mL of water immediately after administering the dose of Evrysdi (Figure O).
See Step E for instructions on how to clean the syringe.
Figure O

D) How to administer a dose of Evrysdi through a nasogastric tube

If Evrysdi is administered through a nasogastric tube, ask your doctor or nurse to
demonstrate how to check the nasogastric tube before administering Evrysdi.

Step D1
Insert the oral syringe tip into the nasogastric
tube. Slowly push the plunger all the way down to
administer the full dose of Evrysdi (Figure P).
Figure P

Step D2
Check that no medicine remains in the oral
syringe (Figure Q).
Figure Q

Step D3
Flush the nasogastric tube with 10-20 mL of
water immediately after administering the dose of
Evrysdi (Figure R).
See step E for instructions on how to clean the
syringe.
Figure R

E) How to clean the oral syringe after use

Step E1
Remove the plunger from the oral syringe.
Rinse the barrel of the oral syringe thoroughly under
running water (Figure S).
Figure S

Step E2
Rinse the plunger thoroughly under running water
(Figure T).
Figure T
Step E3
Check that the barrel of the oral syringe and the

plunger are clean.
Place the barrel of the oral syringe and the plunger
on a clean surface in a safe place to dry (Figure U).
Wash your hands.
Figure U Once dry, reassemble the plunger into the barrel
of the oral syringe and store the syringe with the
medicinal product.
Reconstitution Instructions
Evrysdi 0.75 mg/mL
oral solution powder
risdiplam
Reconstitution Instructions
[FOR HEALTHCARE PROFESSIONALS ONLY (E.G. PHARMACISTS)]
Each Evrysdi pack contains (Figure A):

1. 1 cap

2. 1 vial of Evrysdi
3. 1 oral syringe 12 mL (in pouch)
4. 2 oral syringes 6 mL (in pouches)
5. 2 oral syringes 1 mL (in pouches)
6. 1 press-fit vial adapter
7. 1 package leaflet (not shown)
8. 1 reconstitution instructions (not shown) Figure A
9. 1 user manual (not shown)

Important Information about Evrysdi

• Avoid inhaling Evrysdi powder.
• Wear gloves.
• Do not use the powder after the expiry date. The expiry date of the powder is printed on the vial label.
• Do not dispense the reconstituted solution if the solution's expiry date exceeds the original powder's expiry date.
• Avoid contact of the medicinal product with the skin. If the medicinal product comes into contact with the skin, wash the area with water and soap.
• Do not use the medicinal product if any component of the kit is damaged or missing.
• Use purified water or water for injections to reconstitute the medicinal product.
• Do not use oral syringes other than those provided in the pack.

How to Store Evrysdi

• Store the powder (unreconstituted medicinal product) at room temperature (< 25°C) inside the original packaging with the vial tightly closed to protect the medicinal product from moisture.
• Store the solution (reconstituted medicinal product) in the refrigerator (2°C–8°C) and keep it in an upright position inside the packaging.
• Store the oral solution in the original vial and always keep it upright with the cap tightly closed.

Reconstitution

Step 1
Gently tap the bottom of the vial to loosen the
powder (Figure B).
Figure B

Step 2
Remove the cap by pushing it down and then
rotating it to the left (counterclockwise)
(Figure C). Do not discard the cap.
Figure C

Step 3
Carefully pour 79 mL of purified water or water
for injections into the medicinal product vial
(Figure D).
Figure D

Step 4
Hold the medicinal product vial on the table with
one hand.
Insert the press-fit vial adapter into the opening
by pushing it downward with the other hand.
Ensure it is fully pressed against the mouth of the
vial (Figure E).
Figure E

Step 5
Replace the cap on the vial. Turn the cap to the
right (clockwise) to close the vial.
Ensure it is completely closed, then shake well
for 15 seconds (Figure F).
Wait 10 minutes to obtain a clear solution.
Afterwards, shake again for another 15 seconds.
Figure F
Step 6
Calculate the expiry date 64 days after
reconstitution (Note: the day of reconstitution

is counted as day 0. For example, if the
reconstitution date is 1 April, the expiry date
after reconstitution will be 4 June).
Write the expiry date of the solution on the
vial label (Figure G) and on the packaging.
Replace the vial in its original packaging, with
syringes (in pouches), package leaflet, and user
Figure G manual.
Store the packaging in the refrigerator
(2°C–8°C).

Package leaflet: Information for the patient

Evrysdi 5 mg film-coated tablets

risdiplam
Please read this entire leaflet carefully before taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you/for your child only. Do not give it to others, even if their symptoms appear to be the same as yours or your child’s, as it could be harmful.
• If you or your child experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist or nurse. See section 4.
• Although this leaflet uses the term "you", the information applies to you, the caregiver, or your child.

Contents of this leaflet

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

1. What Evrysdi is and what it is used for

Evrysdi contains the active substance risdiplam. It belongs to a group of medicines known as
“pre-mRNA splicing modifiers”.
Evrysdi is used for the treatment of spinal muscular atrophy (SMA) in adults and children.

• SMA is an inherited, genetic disease.
• It is caused by a deficiency of a protein called SMN (survival motor neuron) in the body.

The lack of SMN protein can lead to the loss of motor neurons. Motor neurons are nerve cells that control muscles.

• This condition causes muscle weakness and wasting.
• This can make everyday movements difficult, such as head and neck control, sitting, crawling, and walking.
• Muscles used for breathing and swallowing may also become weak.

How Evrysdi works
Evrysdi works by helping the body produce more SMN protein.

• This results in reduced loss of motor neurons and improved muscle function in people with SMA.

In infants with type 1 SMA, Evrysdi may:

• increase life expectancy;
• reduce the need for a ventilator to assist breathing;
• preserve the ability to feed by mouth.

In children (from young children to adolescents) and adults with type 2 and type 3 SMA, Evrysdi may:

• stop the worsening of muscle control;
• improve muscle control.

2. What you need to know before taking Evrysdi

Do not take Evrysdi:

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

If you have any doubts, speak with your doctor, pharmacist, or nurse before taking Evrysdi.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Evrysdi.
Treatment with Evrysdi may harm the fetus 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 particular, inform your doctor, pharmacist, or nurse if you are taking or have previously taken any of the following medicines:

• metformin, a medicine used to treat type 2 diabetes;
• medicines for the treatment of SMA.

Pregnancy
Before starting treatment with this medicine, your doctor will ask you to undergo a pregnancy test. This is because Evrysdi may have harmful effects on the fetus.

• Do not take this medicine if you are pregnant.
• You must avoid becoming pregnant:
  • during treatment with Evrysdi and
  • for one month after stopping treatment with Evrysdi. If you become pregnant during treatment, inform your doctor immediately. You and your doctor will decide together what is best for you and the fetus.

Contraception
Women
You must use a highly effective method of contraception:

• during treatment with this medicine and
• for one month after stopping treatment with this medicine.

Discuss with your doctor the highly effective contraceptive methods you and your partner can use.
Men
If your partner is of childbearing age, you must avoid any pregnancy.
Use a condom:

• during treatment with this medicine and
• for 4 months after stopping treatment with this medicine.

Discuss with your doctor the highly effective contraceptive methods you and your partner can use.
Breast-feeding
You must not breast-feed while taking this medicine, as this medicine may pass into breast milk and may have harmful effects on the baby.
Discuss with your doctor the possibility of stopping breast-feeding or stopping treatment with Evrysdi.
Male fertility
Evrysdi may reduce male fertility during treatment and up to 4 months after the last dose.

• If you are planning to have a child, consult your doctor.
• It is important not to donate sperm during treatment and for 4 months following the last dose of this medicine.

Driving and using machines
It is unlikely that this medicine will affect your ability to drive or operate machinery.
Evrysdi contains sodium
Evrysdi contains a small amount of sodium (salt), less than 1 mmol (23 mg) of sodium. This means it is essentially “sodium-free” and can be used by people on a low-sodium diet.

3. How to take Evrysdi

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

You will receive Evrysdi blister packs containing film-coated tablets, referred to as "tablets" in this leaflet. This medicine is also available as an oral solution. Your doctor will help you choose the formulation suitable for you.

Evrysdi dose
If you are taking Evrysdi film-coated tablets, the dose is 5 mg (one tablet) once daily. You must take the daily dose as instructed by your doctor.

• Do not change the dose without first consulting your doctor.

When and how to take Evrysdi
Read the “Instructions for use” at the end of this leaflet. Follow these instructions carefully, which show exactly how to prepare and take Evrysdi as a mixture.

Take Evrysdi:

• once daily, at approximately the same time each day; this will help you remember to take your medicine;
• with or without food.

There are two ways your doctor may instruct you to take Evrysdi film-coated tablets:

• take Evrysdi by mouth. Swallow each tablet whole with a small amount of water.
  • Do not cut, crush, or chew the tablets. Or
• take Evrysdi by mouth after dispersing it in a small amount of room-temperature water.
  • Do not mix Evrysdi with any liquids other than water.
  • Take the Evrysdi tablet immediately after mixing with water. If the mixture is not taken within 10 minutes of adding water, discard the mixture and prepare a new dose.
  • Do not expose the prepared Evrysdi mixture to direct sunlight.
  • Avoid contact of the Evrysdi tablet mixture with skin or eyes. If Evrysdi comes into contact with the skin, wash the area thoroughly with soap and water. If Evrysdi comes into contact with the eyes, rinse them thoroughly with water.
  • Do not administer the mixture through a feeding tube.

Duration of treatment with Evrysdi
Your doctor will tell you how long you should take Evrysdi. Do not stop treatment with Evrysdi unless instructed to do so by your doctor.

If you take more Evrysdi than you should
If you take more Evrysdi than prescribed, contact your doctor immediately or go to the nearest hospital.

• Take the medicine pack and this leaflet with you.

If you forget to take Evrysdi or vomit after taking a dose
If you forget to take a dose:

• If less than 6 hours have passed since your usual time of taking Evrysdi, take the missed dose as soon as you remember.
• If more than 6 hours have passed since your usual time of taking Evrysdi, skip the missed dose and take the next dose at your usual time. Do not take a double dose to make up for a forgotten dose.

If you vomit after taking Evrysdi:

• Do not take an extra dose. Instead, take your next dose at the usual time the following day.

If you spill Evrysdi
If you spill the mixture prepared from the Evrysdi tablet, wipe the area with a dry paper towel and then clean it with soap and water. Dispose of the paper towel in the waste and wash your hands thoroughly with soap and water.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Very common: may affect more than 1 in 10 people

• diarrhoea
• rash
• headache
• fever

Common: may affect up to 1 in 10 people

• nausea
• mouth ulcers
• bladder infection
• joint pain

Not known: frequency cannot be estimated from the available data

• inflammation of small blood vessels mainly in the skin (cutaneous vasculitis).

Reporting of side effects

If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system referred to in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Evrysdi

• Keep this medicine out of the sight and reach of children.
• This medicine does not require any special storage temperature.
• Store in the original packaging to protect the medicine from moisture.

Do not use this medicine after the expiry date stated on the carton and blister after
the word “Exp”. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Evrysdi contains

• The active substance in the film-coated tablet is risdiplam.
• Each film-coated tablet contains 5 mg of risdiplam.
• The other components are tartaric acid (E 334), mannitol (E 421), microcrystalline cellulose, anhydrous colloidal silica (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).

Description of the appearance of Evrysdi and contents of the pack

• Evrysdi tablets are light yellow, round, biconvex, film-coated tablets with "EVR" engraved on one side.
• Evrysdi is supplied in packs containing 28 x 1 film-coated tablet (4 perforated aluminium blisters for single-dose units, each containing 7 tablets).
  • As a reminder for daily dosing, each blister is marked with abbreviated names of the days of the week:

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 further information about this medicinal product, please contact the local representative of the marketing authorisation holder:
België/Belgique/Belgien, Latvija
Luxembourg/Luxemburg Roche Latvija SIA
N.V. Roche S.A. Tel: +371 - 6 7039831
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11
България Lietuva
Рош България ЕООД UAB “Roche Lietuva”
Tel: +359 2 474 5444 Tel: +370 5 2546799
Česká republika Magyarország
Roche s. r. o. Roche (Magyarország) Kft.
Tel: +420 - 2 20382111 Tel: +36 1 279 4500
Danmark Nederland
Roche Pharmaceuticals A/S Roche Nederland B.V.
Tlf: +45 - 36 39 99 99 Tel: +31 (0) 348 438050
Deutschland Norge
Roche Pharma AG Roche Norge AS
Tel: +49 (0) 7624 140 Tlf: +47 - 22 78 90 00
Eesti Österreich
Roche Eesti OÜ Roche Austria GmbH
Tel: + 372 - 6 177 380 Tel: +43 (0) 1 27739
Ελλάδα, Κύπρος Polska
Roche (Hellas) A.E. Roche Polska Sp.z o.o.
Ελλάδα Tel: +48 - 22 345 18 88
Τηλ: +30 210 61 66 100
España Portugal
Roche Farma S.A. Roche Farmacêutica Química, Lda
Tel: +34 - 91 324 81 00 Tel: +351 - 21 425 70 00
France România
Roche România S.R.L.
Roche
Tel: +40 21 206 47 01
Tél: +33 (0) 1 47 61 40 00
Hrvatska Slovenija
Roche d.o.o. Roche farmacevtska družba d.o.o.
Tel: +385 1 4722 333 Tel: +386 - 1 360 26 00
Ireland, Malta Slovenská republika
Roche Slovensko, s.r.o.
Roche Products (Ireland) Ltd.
Tel: +421 - 2 52638201
Ireland/L-Irlanda
Tel: +353 (0) 1 469 0700
Ísland Suomi/Finland
Roche Pharmaceuticals A/S Roche Oy
c/o Icepharma hf Puh/Tel: +358 (0) 10 554 500
Sími: +354 540 8000
Italia Sverige
Roche S.p.A. Roche AB
Tel: +39 - 039 2471 Tel: +46 (0) 8 726 1200
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.
Instructions for use – Administration
Evrysdi film-coated tablets
These Instructions for Use contain information on how to prepare and take Evrysdi.

• The information contained in these Instructions for Use refers to the administration or taking of this medicine, but in this leaflet the term "take" is used for simplicity.

Before you start
Read these Instructions for Use before taking Evrysdi film-coated tablets for the first time and every time you receive a new prescription. They may contain new information.
Evrysdi film-coated tablets can be swallowed whole or mixed with a small amount of water at room temperature and taken orally.
Do not administer Evrysdi film-coated tablets via a feeding tube.
Important information

• Your doctor, pharmacist or nurse will show you how to prepare and take Evrysdi tablets. Always take Evrysdi exactly as instructed by your doctor.
• Do not take or administer this medicine until you have been shown how to correctly prepare and take Evrysdi.
• Wash your hands before and after preparing or taking Evrysdi.
• Check the expiry date and inspect the product for damage before use. Do not use if expired or damaged.
• Avoid contact of the mixture obtained from the Evrysdi tablet with skin or eyes. If the mixture from the Evrysdi tablet comes into contact with the skin, wash the area with soap and water. If the mixture comes into contact with the eyes, rinse them thoroughly with water.
• Keep the mixture obtained from the Evrysdi tablet protected from sunlight.
• If you spill the mixture obtained from the Evrysdi tablet, wipe the area with a dry paper towel and then clean it with soap and water. Dispose of the paper towel in the waste and wash your hands thoroughly 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 in liquid form by mixing 1 tablet in at least 1 teaspoon (5 mL) of water at room temperature.
• Do not chew, cut or crush the tablet.
• Do not mix Evrysdi with liquids other than water.
• Do not take the mixture obtained from the tablet if more than 10 minutes have passed since adding water to the tablet. Dispose of the mixture according to local regulations and prepare a new dose.
• Do not take an extra dose if you vomit at any time after taking Evrysdi.

	Prepare to take one Evrysdi tablet
Step 1. Wash your hands (Figure A).		Figure A
Step 2. Remove 1 Evrysdi tablet from the blister pack (Figure B).		Figure B

Option A: Swallow the Evrysdi tablet whole
Step A1
Swallow the tablet whole with a little water.
Do not chew, cut, or crush the tablet.
Do not take it with liquids other than water.
Step A2
Wash your hands with soap and water.
Option B: Take the Evrysdi tablet mixed in water
What you need to mix Evrysdi with water:
1 Evrysdi tablet
a clean, empty glass
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 into a small glass and add 1 tablet. ●Do not use liquids other than water, ●Keep the mixture away from sunlight.	Figure C
Step B2 Gently swirl the glass until the solution is completely mixed (this may take up to 3 minutes) (Figure C).
Step B3 Drink immediately within 10 minutes after adding water to the tablet (Figure D).	Figure D
Step B4 Fill the glass with at least 1 tablespoon (15 mL) of water and swirl to collect any remaining medicine inside the glass (Figure E).	Figure E
Step B5 Drink immediately (Figure F).	Figure F
Step B6 Wash your hands with water and soap.

	Storage of EVRYSDI
This medicinal product does not require any special temperature storage conditions. • Store in the original packaging to protect the medicine from moisture. • Keep Evrysdi and all medicines out of the sight and reach of children.