Patient Information Leaflet

Evrysdi 0.75 mg/ml powder for oral solution

Risdiplam

This medicine is subject to additional monitoring, which will speed up the detection of any new information about its safety. You can contribute by reporting any side effects you may experience. The final part of section 4 includes information on how to report these side effects.

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

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

What is Evrysdi

Evrysdi is a medication that contains the active ingredient risdiplam.

What is Evrysdi used for

Evrysdi is used to treat spinal muscular atrophy (SMA), a genetic disease.

What is spinal muscular atrophy

SMA is caused by a lack of a protein called survival motor neuron protein (SMN) in the body. The lack of SMN protein can cause you or your child to lose motor neurons, which are nerve cells that control muscles. This leads to muscle weakness and muscle mass loss that can affect daily movements such as head and neck control, sitting, crawling, and walking. Muscles used for breathing and swallowing can also weaken.

How Evrysdi works

Risdiplam, the active ingredient in Evrysdi, acts by helping the body to produce more SMN protein. This results in fewer motor neurons being lost, which can improve muscle function in people with SMA.

In SMA Type 1 babies treated in clinical trials for 1 year, Evrysdi has helped:

• to increase life expectancy and reduce the need for a ventilator to help them breathe, compared to untreated SMA babies (it would be expected that only 25% of untreated babies would be alive without permanent ventilation after 14 months of age, compared to 85% of patients after 1 year of Evrysdi treatment),
• to maintain the ability to feed them orally in 83% of patients.

In children (from small to adolescents) and adults with SMA Type 2 and 3, Evrysdi may maintain or improve muscle control.

Do not take Evrysdi:

• If you or your child is allergic to risdiplam or any of the other excipients in this medication (listed in section6).

Consult your doctor or pharmacist before you or your child starts taking Evrysdi if you are unsure.

Warnings and precautions

Consult your doctor, nurse, or pharmacist before you or your child starts taking Evrysdi.

Treatment with Evrysdi may harm a fetus or affect male fertility. See “Pregnancy, contraception, breastfeeding, and male fertility” for more information.

Other medications and Evrysdi

Inform your doctor or pharmacist if you or your child is taking, has taken recently, or may need to take any other medication in the future.

Particularly, inform your doctor, pharmacist, or nurse if you are taking or have received in the past any of the following medications:

• metformin – a medication used to treat type II diabetes
• medications for the treatment of amyotrophic lateral sclerosis (ALS)

Pregnancy, contraception, breastfeeding, and male fertility

Pregnancy

• Do not take Evrysdi if you are pregnant. This is because taking this medication during pregnancy may harm the fetus.
• Your doctor may perform a pregnancy test before starting treatment with Evrysdi. This is because Evrysdi may harm the fetus.
• If you become pregnant while taking Evrysdi, inform your doctor immediately.

You and your doctor will decide what is best for you and the fetus.

Contraception

For women

Do not become pregnant:

• during treatment with Evrysdi and
• for one month after stopping Evrysdi.

Discuss reliable contraceptive methods with your doctor during treatment and for one month after stopping treatment.

For men

If your partner is a fertile woman, avoid pregnancy. Use reliable contraceptive methods (e.g. condoms):

• during treatment with Evrysdi and
• for 4 months after stopping Evrysdi.

Consult your healthcare professional about reliable contraceptive methods to use.

Breastfeeding

Do not breastfeed your child while taking this medication. This is because Evrysdi may pass into breast milk and, therefore, may harm the baby.

Discuss with your doctor whether you should stop breastfeeding or stop taking Evrysdi.

Male fertility

According to animal findings, Evrysdi may reduce male fertility during treatment and for 4 months after the last dose. If you are planning to have a child, consult your doctor for advice.

Do not donate sperm during treatment and for 4months after the last dose of Evrysdi.

Driving and operating machinery

It is unlikely that Evrysdi will affect your ability to drive and use machines.

Evrysdi contains sodium

Evrysdi contains a small amount of sodium (salt) – there is less than 1mmol of sodium (23mg) even at the maximum daily dose of 5mg (6.6ml of oral solution 0.75mg/ml). This means that it is, essentially, “sodium-free” and can be used by people on a low-sodium diet.

Evrysdi contains 0.375mg of sodium benzoate per ml. Sodium benzoate may increase the risk of jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks of age).

Evrysdi contains isomaltose

Evrysdi contains 2.97mg of isomaltose per ml. If your doctor has told you that you or your child has an intolerance to certain sugars, consult with them before taking this medication.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again. You must receive Evrysdi in the form of a liquid, inside a bottle. If the medication in the bottle is a powder, do not use it and contact your pharmacist.

You must also read carefully and follow theleafletattached “Instructions for use” on how totake or administer Evrysdi.

How much Evrysdi to take

• Adolescents and adults:The daily dose of Evrysdi is 5mg (6.6ml of the oral solution).
• Infants and children:Your doctor will decide the correct dose of Evrysdi based on the age and weight of your child.

You or your child must take the daily dose indicated by your doctor.Do not modify the dose without talking to your doctor.

When and how to take Evrysdi

• Evrysdi is a liquid that the pharmacist prepares and to which reference is made in this prospectus as a“solution” or “medication”.
• Take Evrysdi once a day approximately at the same time every day. This will help you remember when to take the medication.
• Drink water after taking the medication. Do not mix this medication with milk or powdered milk.
• Take or administer Evrysdi immediately after extracting the medication in the oral syringe. If it is not taken within the next 5 minutes, discard the medication from the oral syringe and extract a new dose.
• If Evrysdi comes into contact with your skin or your child's skin, wash the area with water and soap.

Read the “Instructions for use” leaflet

Aleafletof “Instructions for use” is included in the packaging, in which it is indicated how to extract the dose using the reusable oral syringe provided. You (or your child) can take the medication:

• by mouth,
• through a gastrostomy tube or
• through a nasogastric tube.

How long to take Evrysdi

Your doctor will tell you how long to take Evrysdi you or your child. Do not interrupt the treatment with Evrysdi unless the doctor tells you to.

If you or your child take more Evrysdi than you should

If you take more Evrysdi than you should, consult a doctor or go to the hospital immediately. Bring the medication packaging and this prospectus with you.

If you or your child forget to take Evrysdi, or vomit after administering the dose

• If it has not been 6hours since you or your child normally take Evrysdi, take the missed dose as soon as you remember.
• If more than 6hours have passed since you or your child normally take Evrysdi, skip the missed dose and take the next dose at the usual time. Do not take a double dose to compensate for the missed dose.
• If you or your child vomit after taking a dose of Evrysdi, do not take an additional dose. Instead, take the next dose the following day at your usual time.

If you spill Evrysdi

If you spill Evrysdi, dry the area with a paper towel and clean it with soap and water. Throw away the paper towel and wash your hands thoroughly with soap and water.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

Very Common:may affect more than 1 in 10people

• diarrhea
• hives
• headache
• fever

Common:may affect up to 1 in 10people

• nausea
• mouth ulcers
• urinary tract infection
• joint pain

The following adverse effect has been reported since the start of Evrysdi marketing, however, the frequency with which it occurs is unknown:

• Small blood vessel inflammation that mainly affects the skin (cutaneous vasculitis).

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse,even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.* By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

• Maintain this medication out of the sight and reach of children.
• Store the oral solution in the refrigerator (between 2°C and 8°C). If necessary, you or your caregiver can store the oral solution at room temperature (below 40°C) for a maximum of 120 hours (5 days) in total. Store the oral solution in the refrigerator again when it is no longer necessary to store it at room temperature.
• Monitor the total time it is out of the refrigerator (below 40°C). As previously indicated, the sum of the time intervals out of the refrigerator should not exceed 120 hours.
• The oral solution is stable for 64 days after preparation by the pharmacist, provided it is stored in the refrigerator between 2°C and 8°C. The pharmacist will note the expiration date on the label of the bottle and on the original packaging in “Discard after”. Do not use this solution after the date indicated in “Discard after” or discard the medication if the bottle has been stored at room temperature (below 40°C) for more than 120 hours (5 days) in total.
• Discard the medication if the bottle has been stored above 40°C at any time.
• Store the medication in the original bottle to protect it from light.
• Store the medication bottle upright, with the cap perfectly closed.
• Once the medication has been drawn into the oral syringe, use Evrysdi immediately. Do not store the Evrysdi solution in the syringe.

Medications should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Evrysdi

• The active ingredient of the oral solution is risdiplam.
• Each ml of the oral solution contains 0.75 mg of risdiplam.
• The other excipients are mannitol (E 421), isomaltose (E 953), strawberry flavor, tartaric acid (E 334), sodium benzoate (E 211), macrogol/polietilenglycol 6000, sucralose, ascorbic acid (E 300), and disodium edetate (see Section 2 “Evrysdi contains sodium” and “Evrysdi contains isomaltose”).

Appearance of Evrysdi and contents of the package

• Oral solution powder, which is provided as an oral solution after preparation by the pharmacist.
• The oral solution is yellow-green to yellow in color and has a strawberry flavor, the volume of the solution is 80 ml.
• Each package contains 1 bottle, 1 bottle adapter, and reusable amber-colored oral syringes (2 of 1 ml, 2 of 6 ml, and 1 of 12 ml), with graduations to help extract the correct dose.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Responsible for Manufacturing

Roche Registration AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

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

Last update date of this leaflet:

Other sources of information

The detailed information about this medicine is available on the website of the European Medicines Agency:https://www.ema.europa.eu.

Instructions for use - Administration

Evrysdi 0.75 mg/ml powder for oral solution

risdiplam

Please read and understand theseInstructions for usebefore starting to use Evrysdi. These instructions show how to prepare and administer Evrysdi using an oral syringe, gastrostomy tube (G-tube) or nasogastric tube (NG-tube).

If you are unsure about how to use Evrysdi, contact your doctor or pharmacist.

Evrysdi should come as a liquid in a bottle when you receive it. The pharmacist prepares the oral solution of Evrysdi. If the medicine in the bottle is a powder,do notuse it and contact your pharmacist.