Evrysdi

What is Evrysdi?

Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in adults and children 2 months of age and older. It is not known if Evrysdi is safe and effective in children under 2 months of age.

What should I tell my healthcare provider before taking Evrysdi?

Before taking Evrysdi, tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems.
• are pregnant or plan to become pregnant. If you are pregnant, or are planning to become pregnant, ask your healthcare provider for advice before taking this medicine. Evrysdi may harm your unborn baby.
• are a woman who can become pregnant:
  • Before you start your treatment with Evrysdi, your healthcare provider may test you for pregnancy. Because Evrysdi may harm your unborn baby, you and your healthcare provider will decide if taking Evrysdi is right for you during this time.
  • Talk to your healthcare provider about birth control methods that may be right for you. Use birth control while on treatment and for at least 1 month after stopping Evrysdi.
• are an adult male planning to have children: Evrysdi may affect a man’s ability to have children (fertility). If this is of concern to you, make sure to ask a healthcare provider for advice.
• are breastfeeding or plan to breastfeed. It is not known if Evrysdi passes into breast milk and may harm your baby. If you plan to breastfeed, discuss with your healthcare provider about the best way to feed your baby while on treatment with Evrysdi.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Description

EVRYSDI for oral solution contains risdiplam, which is a survival of motor neuron 2 (SMN2)-directed RNA splicing modifier.

The chemical name of risdiplam is 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8 dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido-4H-[1,2-a]pyrimidin-4-one. Risdiplam has a molecular weight of 401.46 g/mol.

The molecular formula of risdiplam is C22H23N7O and the chemical structure is shown below.

EVRYSDI is supplied as a powder in an amber glass bottle. Each bottle contains 60 mg of risdiplam. The inactive ingredients of EVRYSDI are: ascorbic acid, disodium edetate dihydrate, isomalt, mannitol, polyethylene glycol 6000, sodium benzoate, strawberry flavor, sucralose, and tartaric acid.

The powder is constituted with purified water to yield 60 mg/80 mL (0.75 mg/mL) of risdiplam after constitution

Mechanism of Action

Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier designed to treat patients with spinal muscular atrophy (SMA) caused by mutations in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, risdiplam was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein in the brain.

In vitro and in vivo data indicate that risdiplam may cause alternative splicing of additional genes, including FOXM1 and MADD. FOXM1 and MADD are thought to be involved in cell cycle regulation and apoptosis, respectively, and have been identified as possible contributors to adverse effects seen in animals.

How should I take Evrysdi?

See the detailed Instructions for use that comes with Evrysdi for information on how to take or give Evrysdi oral solution.

• You should receive Evrysdi from the pharmacy as a liquid that can be given by mouth or through a feeding tube. The liquid solution is prepared by your pharmacist. If the medicine in the bottle is a powder, do not use it. Contact your pharmacist for a replacement.
• Avoid getting Evrysdi 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.

Taking Evrysdi

• Your healthcare provider will tell you how long you or your child needs to take Evrysdi. Do not stop treatment with Evrysdi unless your healthcare provider tells you to.
• For infants and children, your healthcare provider will determine the daily dose of Evrysdi needed based on your child’s age and weight. For adults, take 5 mg of Evrysdi daily.
  • Take Evrysdi exactly as your healthcare provider tells you to take it. Do not change the dose without talking to your healthcare provider.
• Take Evrysdi 1 time daily after a meal (or after breastfeeding for a child) at approximately the same time each day. Drink water afterwards to make sure Evrysdi has been completely swallowed.
• Do not mix Evrysdi with formula or milk.
• If you are unable to swallow and have a nasogastric or gastrostomy tube, Evrysdi can be given through the tube.
• If you miss a dose of Evrysdi:
  • If you remember the missed dose within 6 hours of when you normally take Evrysdi, then take or give the dose. Continue taking Evrysdi at your usual time the next day.
  • If you remember the missed dose more than 6 hours after you normally take Evrysdi, skip the missed dose. Take your next dose at your usual time the next day.
• If you do not fully swallow the dose, or you vomit after taking a dose, do not take another dose of Evrysdi to make up for that dose. Wait until the next day to take the next dose at your usual time.

Reusable Oral Syringes

• Your pharmacist will provide you with the reusable oral syringes that are needed for taking your medicine and explain how to use them. Wash the syringes per instructions after use. Do not throw them away.
• Use the reusable oral syringes provided by your pharmacist (you should receive 2 identical oral syringes) to measure your or your child’s dose of Evrysdi, as they are designed to protect the medicine from light. Contact your healthcare provider or pharmacist if your oral syringes are lost or damaged.
• Once transferred from the bottle to the oral syringe, take Evrysdi right away. Do not store the Evrysdi solution in the syringe. If Evrysdi is not taken within 5 minutes of when it is drawn up, Evrysdi should be thrown away from the reusable oral syringe, and a new dose should be prepared.

What are the possible side effects of Evrysdi?

The most common side effects of Evrysdi include:

• For later-onset SMA:
  • fever
  • diarrhea
  • rash
• For infantile-onset SMA:
  • fever
  • diarrhea
  • rash
  • runny nose, sneezing, sore throat, and cough (upper respiratory infection)
  • lung infection
  • constipation
  • vomiting

These are not all of the possible side effects of Evrysdi. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Evrysdi

Medicines are sometimes prescribed for purposes other than those listed in a patient information guide. Do not use Evrysdi for a condition for which it was not prescribed. Do not give Evrysdi to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Evrysdi that is written for health professionals.

How should I store Evrysdi?

• Store Evrysdi in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze.
• Keep Evrysdi in an upright position in the original amber bottle to protect from light.
• Throw away (discard) any unused portion of Evrysdi 64 days after it is mixed by the pharmacist (constitution). Please see the Discard After date written on the bottle label. (See the Instructions for use that comes with Evrysdi).

Keep Evrysdi and all medicines out of the reach of children.

What are the ingredients in Evrysdi?

Active ingredient: risdiplam

Inactive ingredients: ascorbic acid, disodium edetate dihydrate, isomalt, mannitol, polyethylene glycol 6000, sodium benzoate, strawberry flavor, sucralose, and tartaric acid.

For more information, go to www.EVRYSDI.com or call 1-833-387-9734.

Instructions for use for Evrysdi

Evrysdi [ev-RIZ-dee]
(risdiplam)
for oral solution

Please read and understand this Instructions for Use and the Patient Information guide before you start taking Evrysdi for information about Evrysdi and how to prepare and give Evrysdi through an oral syringe, gastrostomy tube (G-tube), or nasogastric tube (NG-tube).

If you have any questions about how to take Evrysdi, contact your healthcare provider.

Evrysdi should come as a liquid in a bottle when you receive it from the pharmacy. Do not take Evrysdi and contact your pharmacist if the medicine in the bottle is a powder.

Each Evrysdi carton contains (see Figure A):

1 Cap 1 Bottle adapter 1 Evrysdi bottle 2 Reusable oral syringes Instructions for Use (not shown) 1 Prescribing Information and Patient Information (not shown)	Figure A
Reusable Oral Syringe Overview (see Figure B)	Figure B

Important information about Evrysdi

• Ask your healthcare provider to show you the correct oral syringe you should use and how to measure your prescribed daily dose.
• Always use the reusable oral syringes that come with Evrysdi to measure your prescribed daily dose. If your carton does not contain two identical syringes, contact your pharmacist.
• Always take Evrysdi exactly as your healthcare provider tells you to take it.
• Take Evrysdi 1 time daily after a meal at approximately the same time each day.
• Do not take Evrysdi if the bottle adapter is not in the bottle. If the bottle adapter is not in the bottle, contact your pharmacist.
• Do not mix Evrysdi into food or liquids. Do not mix Evrysdi with formula or milk.
• Do not take Evrysdi if the bottle or oral syringes are damaged.
• Avoid getting Evrysdi 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.
• If you spill Evrysdi, dry the area with a dry paper towel and then clean with water. Throw away the paper towel in the trash and wash your hands well with soap and water.
• If there is not enough Evrysdi left in the bottle for your prescribed dose, throw away (discard) the bottle with remaining Evrysdi and used oral syringes according to your local requirements.
• Use a new bottle of Evrysdi to get your prescribed dose.
  Do not mix Evrysdi from the new bottle with the bottle you are currently using.

How to store Evrysdi

Store Evrysdi in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze. Store Evrysdi in the original amber bottle in an upright position with the cap tightly closed. Throw away (discard) any unused portion of Evrysdi 64 days after constitution. Please see the Discard After date written on the bottle label (see Figure C). Ask your pharmacist for the Discard After date if it is not written on the bottle label. Keep Evrysdi and all medicines and syringes out of the reach of children.

Figure C

A) Preparing and withdrawing your dose

How to prepare your dose of Evrysdi

Figure D	Step A1 Remove the cap by pushing it down and then twisting the cap to the left (counterclockwise) (See Figure D). Do not throw away the cap.
Figure E	Step A2 Push the plunger of the oral syringe all the way down to remove any air in the oral syringe (See Figure E).
Figure F	Step A3 Place the Evrysdi bottle on a flat surface. While keeping the bottle in an upright position, insert the syringe tip into the bottle adapter (See Figure F).
Figure G	Step A4 Carefully turn the bottle upside down with the syringe tip firmly inserted into the bottle adapter (See Figure G).
Figure H	Step A5 Slowly pull back on the plunger to withdraw your prescribed dose of Evrysdi. The top of the black plunger stopper must line up with the mL marking on the oral syringe for your prescribed daily dose (See Figure H). After the correct dose is withdrawn, hold the plunger in place to keep the plunger from moving.
Figure I	Step A6 Continue to hold the plunger in place to keep the plunger from moving. Leave the oral syringe in the bottle adapter and turn the bottle to an upright position. Place the bottle onto a flat surface. Remove the oral syringe from the bottle adapter by gently pulling straight up on the oral syringe while holding the plunger in place (See Figure I).
Figure J	Step A7 Hold the oral syringe with the syringe tip pointing up. Check the Evrysdi in the oral syringe. If there are large air bubbles in the oral syringe (See Figure J) or if you have drawn up the wrong dose of Evrysdi, insert the syringe tip firmly into the bottle adapter while the bottle is in an upright position. Push the plunger all the way down so that Evrysdi flows back into the bottle and repeat Steps A4 through A7. Take or give Evrysdi right away after it is drawn up into the oral syringe. If it is not taken within 5 minutes, throw away Evrysdi liquid from your oral syringe into the household trash. Do this by pushing the plunger all the way down to remove Evrysdi from the oral syringe. Prepare a new dose starting with STEP A2.
Figure K	Step A8 Put the cap back on the bottle. Turn the cap to the right (clockwise) to tightly close the bottle (See Figure K). Do not remove the bottle adapter 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”.

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”.

B) How to take a dose of Evrysdi by mouth

Sit upright when taking a dose of Evrysdi by mouth.

Figure L	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 L). Giving Evrysdi into the throat or too fast may cause choking.
Figure M	Step B2 Check that there is no Evrysdi left in the oral syringe (See Figure M)
Figure N	Step B3 Drink about a tablespoon (15 mL) of water right after taking the prescribed dose of Evrysdi to ensure the drug has been completely swallowed (See Figure N). Go to STEP E for cleaning of the syringe

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

If you are giving Evrysdi through a gastrostomy tube, ask your healthcare provider to show you how to inspect the gastrostomy tube before giving Evrysdi.

Figure O	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 O).
Figure P	Step C2 Check that there is no Evrysdi left in the oral syringe (See Figure P).
Figure Q	Step C3 Flush the gastrostomy tube with 10 mL to 20 mL of water right after giving the prescribed dose of Evrysdi (See pFigure Q). Go to STEP E for cleaning of the syringe.

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

If you are giving Evrysdi through a nasogastric tube, ask your healthcare provider to show you how to inspect the nasogastric tube before giving Evrysdi.

Figure R	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 R).
Figure S	Step D2 Check that there is no Evrysdi left in the oral syringe (See Figure S).
Figure T	Step D3 Flush the nasogastric tube with 10 mL to 20 mL of water right after giving the prescribed dose of Evrysdi (See Figure T). Go to STEP E for cleaning of the syringe.

E) How to clean the oral syringe after use

Figure U	Step E1 Remove the plunger from the oral syringe by pulling the plunger away from the syringe until the plunger comes out of the syringe. Rinse the oral syringe barrel well under clean water (See Figure U).
Figure V	Step E2 Rinse the plunger well under clean water (See Figure V).
Figure W	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 W). Wash your hands with soap and water. After the oral syringe barrel and plunger are dry, put the plunger back into the oral syringe barrel and store the syringe with your medicine.

Label

PRINCIPAL DISPLAY PANEL – 60 MG/80 ML BOTTLE CARTON

• NDC 50242-175-07
• Evrysdi®
  (risdiplam)
  for oral solution
• 60 mg/80 mL
  (0.75 mg/mL)
• Attention pharmacist: Evrysdi must be
  constituted with water prior to dispensing.
• 80 mL (2.71 fl oz) total volume after constitution
• Rx only
• Genentech
• 10252477

SRC: NLM .