Evrysdi 0.75 mg/mL powder for oral solution

• 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 or your child 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 or your child get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

Evrysdi is a medicine that contains the active substance risdiplam.

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

SMA is caused by a shortage of a protein called survival motor neuron (SMN) protein in the body. 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 wasting that can affect everyday movements such as head and neck control, sitting, crawling and walking. The muscles used for breathing and swallowing may also become weaker.

Risdiplam, the active substance in Evrysdi, works by helping the body produce more SMN protein. This means fewer motor neurons are lost, which may improve how well muscles work in people with SMA.

In infants with SMA Type 1 treated in clinical trials for 1 year, Evrysdi has helped to:

• increase how long they live and reduce the need for a ventilator to help with breathing compared to untreated infants with SMA (only 25% of untreated infants would be expected to be alive without the need for permanent ventilation beyond 14 months of age compared to 85% of patients after 1 year of treatment with Evrysdi),
• keep the ability to be fed by mouth in 83% of patients.

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

• if you or your child 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 or pharmacist before you or your child take Evrysdi.

Talk to your doctor, nurse or pharmacist before you or your child take Evrysdi.

Treatment with Evrysdi may harm your unborn baby or may affect male fertility. See “Pregnancy, contraception, breast-feeding and male fertility” for more information.

Tell your doctor or pharmacist if you or your child 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 received in the past any of the following medicines:

• metformin – a medicine used to treat type II diabetes
• medicines for the treatment of SMA

Pregnancy

• Do not take Evrysdi if you are pregnant. This is because taking this medicine while you are pregnant could harm your unborn baby.
• Before you start treatment with Evrysdi, your doctor should do a pregnancy test. This is because Evrysdi may harm your unborn baby.
• If you do become pregnant during your treatment with Evrysdi, tell your doctor straight away.

You and your doctor will decide what is best for you and your unborn baby.

Contraception

For women

Do not become pregnant:

• during your treatment with Evrysdi and
• for one month after you stop taking Evrysdi.

Talk to your doctor about reliable methods of birth control that should be used during treatment and for one month after you stop treatment.

For men

If your female partner is of childbearing potential, you need to avoid pregnancy. Use reliable methods of birth control (eg. condoms):

• during your treatment with Evrysdi and
• for 4 months after you stop taking Evrysdi.

Talk to your healthcare provider about reliable methods of birth control that should be used.

Breast-feeding

Do not breast-feed while taking this medicine. This is because Evrysdi may pass into breast milk and may, therefore, harm your baby.

Discuss with your doctor if you should stop breast-feeding or if you should stop taking Evrysdi.

Male fertility

Based on findings in animals, Evrysdi may reduce male fertility while on 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 Evrysdi.

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

Evrysdi contains a small amount of sodium (salt) - there is less than 1 mmol (23 mg) sodium even at the highest daily dose of 5 mg (6.6 mL of 0.75 mg/mL oral solution). This means it is essentially ‘sodium-free’ and can be used by people on a sodium-restricted diet.

Evrysdi contains 0.375 mg of sodium benzoate per mL. Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old).

Evrysdi contains 2.97 mg of isomalt per mL. If you have been told by your doctor that you or your child have an intolerance to some sugars, contact your doctor before taking this medicinal product.

• Adolescents and adults: The daily dose of Evrysdi is 5 mg (6.6 mL of the oral solution).
• Infants and children: Your doctor will choose the right dose of Evrysdi based on your child’s age and weight.

You or your child must take your daily dose as instructed by your doctor. Do not change the dose without speaking with your doctor.

• Evrysdi is a liquid which is prepared by the pharmacist, and is referred to as a ‘solution’ or ‘medicine’ in this leaflet.
• Take Evrysdi once daily after a meal at around the same time each day. This will help you remember when to take your medicine.
• Drink water after taking the medicine. Do not mix the medicine with milk or formula milk.
• Take or give Evrysdi immediately after it is drawn up into the oral syringe. If it is not taken within 5 minutes, discard the medicine from the oral syringe, and withdraw a new dose
• If Evrysdi gets on you or your child’s skin, wash the area with soap and water.

A booklet with ‘Instructions for use’ is included in the pack. It shows you how to withdraw your dose using the re-usable oral syringe given to you. You (or your child) can take the medicine:

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

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

If you or your child 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 it is within 6 hours of when you or your child normally take Evrysdi, take the missed dose as soon as you remember.
• If it is over 6 hours from when you or your child 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 or your child vomits after taking a dose of Evrysdi, do not take an extra dose. Instead, take the next dose at the usual time the next day.

If you spill Evrysdi, dry the area with a dry paper towel and then clean the area with soap and water. Throw away the paper towel in the waste and wash your hands well with soap and water.

If you or your child 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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance in the oral solution is risdiplam.
• Each mL of the oral solution contains 0.75 mg risdiplam.
• The other ingredients are mannitol (E 421), isomalt (E 953), strawberry flavour, tartaric acid (E 334), sodium benzoate (E 211), macrogol/polyethylene glycol 6000, sucralose, ascorbic acid (E 300), disodium edetate dihydrate (see Section 2 ‘Evrysdi contains sodium’ and ‘Evrysdi contains isomalt’).

• Powder for oral solution, which is delivered as an oral solution after preparation by the pharmacist.
• The solution is a greenish yellow to yellow, strawberry flavoured oral solution, the volume of the solution is 80 mL.
• Each carton contains 1 bottle, 1 press-in bottle adaptor, two 1-mL, two 6-mL and one 12-mL re-usable amber oral syringes with markings to help you withdraw the right dose.

• Ask your doctor or pharmacist to show you which oral syringe you should use and how to measure your daily dose.
• Always use the re-usable oral syringes in the pack to measure your daily dose.
• Contact your doctor or pharmacist if your oral syringe(s) is/are lost or damaged. They will advise you about how to continue to take your medicine.
• See “How to select the correct oral syringe for your dose of Evrysdi”. Ask your pharmacist if you have questions on how to select the right oral syringe.
• If the bottle adaptor is not in the bottle, do not use Evrysdi and contact your pharmacist.
• The oral solution may be stored at room temperature (below 40˚C) for no more than a total of 120 hours (5 days). Monitor the total time outside the refrigerator (below 40˚C).
• Do not use Evrysdi after the Discard after date written on the bottle label or if you or your caregiver have stored the bottle at room temperature (below 40˚C) for more than a total of 120 hours (5 days). Ask your pharmacist for the Discard after date if it is not written on the bottle label.
• Discard the medicine if the bottle has been stored for any period of time at above 40˚C.
• Do not mix Evrysdi with milk or formula milk.
• Do not use Evrysdi if the bottle or oral syringes are damaged.
• Avoid getting Evrysdi on your skin. If Evrysdi gets on your skin, wash the area with soap and water.
• If you spill Evrysdi, dry the area with a dry paper towel and then clean the area with soap and water. Throw away the paper towel in the waste and wash your hands well with soap and water.
• If there is not enough Evrysdi left in the bottle for your dose, discard the bottle with remaining Evrysdi and used oral syringes according to your local requirements; use a new bottle of Evrysdi for your full dose. Do not mix Evrysdi from the new bottle with the bottle you are currently using.

1. 1 Evrysdi bottle with bottle adaptor and cap
2. 1 Oral Syringe 12 mL (in pouch)
3. 2 Oral syringes 6 mL (in pouches)
4. 2 Oral syringes 1 mL (in pouches)
5. 1 Instructions for Use booklet (not shown)
6. 1 Package Leaflet (not shown)

Please see section 5 “How to store Evrysdi” of the Package Leaflet for full information.

How to select the correct oral syringe for your dose of Evrysdi

• If your daily dose of Evrysdi is between 0.3 mL and 1 mL, use a 1 mL oral syringe (yellow label).
• If your daily dose of Evrysdi is between 1 mL and 6 mL, use a 6-mL oral syringe (grey label).
• If your daily dose of Evrysdi is more than 6 mL, use a 12-mL oral syringe (brown label).

Ask your doctor or pharmacist about rounding your or your child’s daily dose to the nearest syringe marking.

How to withdraw your dose of Evrysdi

Step A1

Remove the cap by pushing it down and then twisting it to the left (counter-clockwise) (See Figure B). Do not throw away the cap.

Step A2

Push the plunger of the oral syringe all the way down to remove any air in the oral syringe (See Figure C).

Step A3

Keeping the bottle upright, insert the syringe tip into the bottle adaptor (See Figure D).

Step A4

Carefully turn the bottle upside down with the syringe tip firmly inserted into the bottle adaptor (See Figure E).

Step A5

Slowly pull back on the plunger to withdraw your dose of Evrysdi. The top of the black plunger stopper must line up with the mL marking on the oral syringe for your daily dose (See Figure F).

After you have drawn up the correct dose, hold the plunger in place to keep it from moving.

Step A6

Continue to hold the plunger in place to stop it moving. Leave the oral syringe in the bottle adaptor and turn the bottle to an upright position. Place the bottle onto a flat surface. Remove the oral syringe from the bottle adaptor by gently pulling straight up on the oral syringe (See Figure G).

Step A7

Hold the oral syringe with the syringe tip pointing up. Check the medicine in the oral syringe. If there are large air bubbles in the oral syringe (See Figure H) or if you have drawn up the wrong dose of Evrysdi, insert the syringe tip firmly into the bottle adaptor. Push the plunger all the way down so that the medicine flows back into the bottle and repeat Steps A4 to A7.

Take or give Evrysdi immediately after it is drawn up into the oral syringe.

If it is not taken within 5 minutes, discard the medicine from oral syringe and withdraw a new dose.

Step A8

Put the cap back on the bottle. Turn the cap to the right (clockwise) to tightly close the bottle (See Figure I). Do not remove the bottle adaptor from the bottle.

If you are taking your dose of Evrysdi by mouth, follow the instructions in “B) How to take a dose of Evrysdi by mouth”.

If you are taking your dose of Evrysdi through a gastrostomy tube, follow the instructions in “C) How to give a dose of Evrysdi through a gastrostomy tube (G-tube)”.

If you are taking your dose of Evrysdi through a nasogastric tube, follow the instructions in “D) How to give a dose of Evrysdi through a nasogastric tube (NG-tube)”.

Evrysdi’s oral syringes are specifically designed to be compatible with the ENFit^® system. If your feeding tube is not ENFit^® compatible, you may need an ENFit^® transition connector to connect the Evrysdi syringe to your G-tube or NG-tube.

Sit upright when taking a dose volume of Evrysdi by mouth.

Step B1

Place the oral syringe into the mouth with the tip along either cheek.

Slowly push the plunger all the way down to give the full dose of Evrysdi (See Figure J).

Giving Evrysdi into the back of the throat or too fast may cause choking.

Step B2

Check that there is no medicine left in the oral syringe (See Figure K).

Step B3

Drink some water right after taking the dose of Evrysdi (See Figure L).

Go to Step E for cleaning of the syringe.

If you are giving Evrysdi through a gastrostomy tube, ask your doctor or nurse to show you how to inspect the gastrostomy tube before giving Evrysdi.

Step C1

Place the oral syringe tip into the gastrostomy tube. Slowly push the plunger all the way down to give the full dose of Evrysdi (See Figure M).

Step C2

Check that there is no medicine left in the oral syringe (See Figure N).

Step C3

Flush the gastrostomy tube with 10-20 mL of water right after giving the dose of Evrysdi (See Figure O).

Go to Step E for cleaning of the syringe.

If you are giving Evrysdi through a nasogastric tube, ask your doctor or nurse to show you how to inspect the nasogastric tube before giving Evrysdi.

Step D1

Place the oral syringe tip into the nasogastric tube. Slowly press the plunger all the way down to give the full dose of Evrysdi (See Figure P).

Step D2

Check that there is no medicine left in the oral syringe (See Figure Q).

Step D3

Flush the nasogastric tube with 10-20 mL of water right after giving the dose of Evrysdi (See Figure R).

Go to Step E for cleaning of the syringe.

Step E1

Remove the plunger from the oral syringe.

Rinse the oral syringe barrel well under clean water (See Figure S).

Step E2

Rinse the plunger well under clean water (See Figure T).

Step E3

Check that the oral syringe barrel and plunger are clean.

Place the oral syringe barrel and plunger on a clean surface in a safe place to dry (See Figure U).

Wash your hands.

Once dry, reassemble the plunger into the oral syringe barrel and store the syringe with your medicine.