Get your patient on Evrysdi (Risdiplam)

EVRYSDI is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.

• Administer once daily with or without food per the table below (
  2.1 Dosing Information

  EVRYSDI is administered orally once daily with or without food. The recommended dosage is determined by age and body weight (seeTable 1). EVRYSDI tablets are available for patients prescribed the 5 mg dose.

  Table 1 Adult and Pediatric Dosing Regimen by Age and Body Weight

  Age and Body Weight	Recommended Daily Dosage	Dosage Form
  Less than 2 months of age	0.15 mg/kg	EVRYSDI for Oral Solution
  2 months to less than 2 years of age	0.2 mg/kg
  2 years of age and older weighing less than 20 kg	0.25 mg/kg
  2 years of age and older weighing 20 kg or more	5 mg	EVRYSDI for Oral Solution or EVRYSDI Tablet
  ):

• Swallow EVRYSDI tablet whole with water or dispersed in non-chlorinated drinking water (e.g., filtered water). (
  2.2 Important Administration Instructions

  It is recommended that a healthcare provider discuss with the patient or caregiver how to prepare the prescribed daily dose prior to administration of the first dose

  [seeInstructions for Use for EVRYSDI for Oral SolutionandPatient Information].

  EVRYSDI is taken orally once daily with or without food at approximately the same time each day.

  EVRYSDI for Oral Solution

  In infants who are breastfed, EVRYSDI for oral solution can be administered before or after breastfeeding. EVRYSDI cannot be mixed with formula or milk.

  Instruct patients or caregivers to administer the dose using the reusable oral syringe provided.

  EVRYSDI for oral solution must be taken immediately after it is drawn up into the oral syringe. If EVRYSDI is not taken within 5 minutes, EVRYSDI should be discarded from the oral syringe, and a new dose should be prepared.

  Instruct patients to drink water after taking EVRYSDI for oral solution to ensure the drug has been completely swallowed.

  If the patient is unable to swallow and has a nasogastric or gastrostomy tube, EVRYSDI for oral solution can be administered via the tube. The tube should be flushed with water after delivering EVRYSDI for oral solution

  [seeInstructions for Use].

  EVRYSDI Tablets

  Swallow EVRYSDI tablets whole with water. Do not chew, cut, or crush the tablets.

  The EVRYSDI tablet can also be dispersed in one teaspoon (5 mL) of room temperature non-chlorinated drinking water (e.g., filtered water). EVRYSDI tablets must not be dispersed in any liquid other than non-chlorinated drinking water. Do not expose the prepared dispersion to sunlight. Swirl the small cup gently for up to 3 minutes until fully mixed (though some particles will remain). Administer the dispersed tablet immediately. To ensure no particles are left in the small cup, refill it with at least one tablespoon (15 mL) of non-chlorinated drinking water, swirl, and administer immediately again.

  EVRYSDI must be taken immediately after it is dispersed in non-chlorinated drinking water. Discard the prepared dispersion if it is not used within 10 minutes of adding non-chlorinated drinking water.

  Do not administer the prepared dispersion via a nasogastric or gastrostomy tube. If administration through a nasogastric or gastrostomy tube is required, EVRYSDI for oral solution should be used.
  )
• Administer EVRYSDI for oral solution with the provided oral syringe. (
  2.2 Important Administration Instructions

  It is recommended that a healthcare provider discuss with the patient or caregiver how to prepare the prescribed daily dose prior to administration of the first dose

  [seeInstructions for Use for EVRYSDI for Oral SolutionandPatient Information].

  EVRYSDI is taken orally once daily with or without food at approximately the same time each day.

  EVRYSDI for Oral Solution

  In infants who are breastfed, EVRYSDI for oral solution can be administered before or after breastfeeding. EVRYSDI cannot be mixed with formula or milk.

  Instruct patients or caregivers to administer the dose using the reusable oral syringe provided.

  EVRYSDI for oral solution must be taken immediately after it is drawn up into the oral syringe. If EVRYSDI is not taken within 5 minutes, EVRYSDI should be discarded from the oral syringe, and a new dose should be prepared.

  Instruct patients to drink water after taking EVRYSDI for oral solution to ensure the drug has been completely swallowed.

  If the patient is unable to swallow and has a nasogastric or gastrostomy tube, EVRYSDI for oral solution can be administered via the tube. The tube should be flushed with water after delivering EVRYSDI for oral solution

  [seeInstructions for Use].

  EVRYSDI Tablets

  Swallow EVRYSDI tablets whole with water. Do not chew, cut, or crush the tablets.

  The EVRYSDI tablet can also be dispersed in one teaspoon (5 mL) of room temperature non-chlorinated drinking water (e.g., filtered water). EVRYSDI tablets must not be dispersed in any liquid other than non-chlorinated drinking water. Do not expose the prepared dispersion to sunlight. Swirl the small cup gently for up to 3 minutes until fully mixed (though some particles will remain). Administer the dispersed tablet immediately. To ensure no particles are left in the small cup, refill it with at least one tablespoon (15 mL) of non-chlorinated drinking water, swirl, and administer immediately again.

  EVRYSDI must be taken immediately after it is dispersed in non-chlorinated drinking water. Discard the prepared dispersion if it is not used within 10 minutes of adding non-chlorinated drinking water.

  Do not administer the prepared dispersion via a nasogastric or gastrostomy tube. If administration through a nasogastric or gastrostomy tube is required, EVRYSDI for oral solution should be used.
  )
• EVRYSDI for oral solution must be constituted by a healthcare provider prior to dispensing. (
  2.4 Preparation of Powder for Oral Solution by Healthcare Provider

  EVRYSDI powder must be constituted to the oral solution by a pharmacist or other healthcare provider prior to dispensing to the patient.

  Preparation of the EVRYSDI Oral Solution 0.75 mg/mL

  The EVRYSDI "Instructions for Constitution" booklet contains more detailed instructions on the preparation of the oral solution

  [seeInstructions for Constitution]

  .

  Caution should be exercised when handling EVRYSDI powder for oral solution

  .

  Avoid inhalation and direct contact with skin or mucous membranes with the dry powder and the constituted solution. If such contact occurs, wash thoroughly with soap and water; rinse eyes with water. Wear disposable gloves during the preparation and cleanup procedure.

  • Gently tap the bottom of the closed glass bottle to loosen the powder.
  • Remove the cap. Do not throw away the cap.
  • Carefully pour 79 mL of purified water into the EVRYSDI bottle to yield the 0.75 mg/mL oral solution. Do not mix EVRYSDI with formula or milk.
  • Insert the press-in bottle adapter into the bottle opening by pushing it down against the bottle lip. Ensure it is completely pressed against the bottle lip.
  • Re-cap the bottle tightly and shake well for 15 seconds. Wait for 10 minutes. You should have obtained a clear solution. If not, shake well again for another 15 seconds or until you have obtained a clear solution.
  • Write the date of expiration of the constituted oral solution (calculated as 64 days after constitution) and the lot number on the bottle label. Peel off the part of the bottle label that has the expiration date of the powder.
  • Put the bottle back in its original carton.
  • Select the appropriate oral syringes (1 mL, 6 mL, or 12 mL) based on the patient's dosage and remove the other oral syringes from the carton.
  • Dispense with the "Instructions for Use" and FDA-approved patient labeling. Alert patients to read the important handling information described in theInstructions for Use.

  Storage

  Keep the constituted oral solution of EVRYSDI in the original amber bottle to protect from light. Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Discard any unused portion 64 days after constitution. Keep the bottle in an upright position with the cap tightly closed. If refrigeration is not available, EVRYSDI can be kept at room temperature up to 40°C (up to 104°F) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not exceed 5 days.
  )
• See Full Prescribing Information for important preparation and administration instructions. (
  2.2 Important Administration Instructions

  It is recommended that a healthcare provider discuss with the patient or caregiver how to prepare the prescribed daily dose prior to administration of the first dose

  [seeInstructions for Use for EVRYSDI for Oral SolutionandPatient Information].

  EVRYSDI is taken orally once daily with or without food at approximately the same time each day.

  EVRYSDI for Oral Solution

  In infants who are breastfed, EVRYSDI for oral solution can be administered before or after breastfeeding. EVRYSDI cannot be mixed with formula or milk.

  Instruct patients or caregivers to administer the dose using the reusable oral syringe provided.

  EVRYSDI for oral solution must be taken immediately after it is drawn up into the oral syringe. If EVRYSDI is not taken within 5 minutes, EVRYSDI should be discarded from the oral syringe, and a new dose should be prepared.

  Instruct patients to drink water after taking EVRYSDI for oral solution to ensure the drug has been completely swallowed.

  If the patient is unable to swallow and has a nasogastric or gastrostomy tube, EVRYSDI for oral solution can be administered via the tube. The tube should be flushed with water after delivering EVRYSDI for oral solution

  [seeInstructions for Use].

  EVRYSDI Tablets

  Swallow EVRYSDI tablets whole with water. Do not chew, cut, or crush the tablets.

  The EVRYSDI tablet can also be dispersed in one teaspoon (5 mL) of room temperature non-chlorinated drinking water (e.g., filtered water). EVRYSDI tablets must not be dispersed in any liquid other than non-chlorinated drinking water. Do not expose the prepared dispersion to sunlight. Swirl the small cup gently for up to 3 minutes until fully mixed (though some particles will remain). Administer the dispersed tablet immediately. To ensure no particles are left in the small cup, refill it with at least one tablespoon (15 mL) of non-chlorinated drinking water, swirl, and administer immediately again.

  EVRYSDI must be taken immediately after it is dispersed in non-chlorinated drinking water. Discard the prepared dispersion if it is not used within 10 minutes of adding non-chlorinated drinking water.

  Do not administer the prepared dispersion via a nasogastric or gastrostomy tube. If administration through a nasogastric or gastrostomy tube is required, EVRYSDI for oral solution should be used.
  ,
  2.4 Preparation of Powder for Oral Solution by Healthcare Provider

  EVRYSDI powder must be constituted to the oral solution by a pharmacist or other healthcare provider prior to dispensing to the patient.

  Preparation of the EVRYSDI Oral Solution 0.75 mg/mL

  The EVRYSDI "Instructions for Constitution" booklet contains more detailed instructions on the preparation of the oral solution

  [seeInstructions for Constitution]

  .

  Caution should be exercised when handling EVRYSDI powder for oral solution

  .

  Avoid inhalation and direct contact with skin or mucous membranes with the dry powder and the constituted solution. If such contact occurs, wash thoroughly with soap and water; rinse eyes with water. Wear disposable gloves during the preparation and cleanup procedure.

  • Gently tap the bottom of the closed glass bottle to loosen the powder.
  • Remove the cap. Do not throw away the cap.
  • Carefully pour 79 mL of purified water into the EVRYSDI bottle to yield the 0.75 mg/mL oral solution. Do not mix EVRYSDI with formula or milk.
  • Insert the press-in bottle adapter into the bottle opening by pushing it down against the bottle lip. Ensure it is completely pressed against the bottle lip.
  • Re-cap the bottle tightly and shake well for 15 seconds. Wait for 10 minutes. You should have obtained a clear solution. If not, shake well again for another 15 seconds or until you have obtained a clear solution.
  • Write the date of expiration of the constituted oral solution (calculated as 64 days after constitution) and the lot number on the bottle label. Peel off the part of the bottle label that has the expiration date of the powder.
  • Put the bottle back in its original carton.
  • Select the appropriate oral syringes (1 mL, 6 mL, or 12 mL) based on the patient's dosage and remove the other oral syringes from the carton.
  • Dispense with the "Instructions for Use" and FDA-approved patient labeling. Alert patients to read the important handling information described in theInstructions for Use.

  Storage

  Keep the constituted oral solution of EVRYSDI in the original amber bottle to protect from light. Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Discard any unused portion 64 days after constitution. Keep the bottle in an upright position with the cap tightly closed. If refrigeration is not available, EVRYSDI can be kept at room temperature up to 40°C (up to 104°F) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not exceed 5 days.
  )

EVRYSDI for oral solution: 60 mg as a light yellow, pale yellow, yellow, greyish yellow, greenish yellow, or light green powder for constitution. Following constitution, the volume of the greenish yellow to yellow solution is 80 mL, providing 60 mg/80 mL (0.75 mg/mL) risdiplam.

EVRYSDI tablet: 5 mg as a pale yellow film-coated tablet, round and curved, with EVR debossed on one side.

Pregnancy: Based on animal data, may cause fetal harm. (

None.

The most common adverse reactions in later-onset SMA (incidence at least 10% of patients treated with EVRYSDI and more frequent than control) were fever, diarrhea, and rash. (

The most common adverse reactions in infantile-onset SMA were similar to those observed in later-onset SMA patients. Additionally, adverse reactions with an incidence of at least 10% were upper respiratory tract infection, lower respiratory tract infection, constipation, vomiting, and cough. (

Avoid coadministration with drugs that are substrates of multidrug and toxin extrusion (MATE) transporters. (

EVRYSDI for oral solution and EVRYSDI tablets for oral use contain 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. Risdiplam demonstrates pH-dependent aqueous solubility; the greatest solubility is at low pH, and solubility decreases with increasing pH. Risdiplam has a pKa₁ of 3.78 (base) and pKa₂ of 6.62 (base).

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

EVRYSDI for oral solution 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

Each EVRYSDI tablet contains 5 mg of risdiplam. The inactive ingredients of EVRYSDI tablet are colloidal silicon dioxide, crospovidone, mannitol, microcrystalline cellulose, polyethylene glycol 3350, polyvinyl alcohol, sodium stearyl fumarate, strawberry flavor, talc, tartaric acid, titanium dioxide, and yellow iron oxide.

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.

Risdiplam was not carcinogenic in Tg.rasH2 mice when administered at oral doses of up to 9 mg/kg/day for 26 weeks.

In a 2-year carcinogenicity study in rats, oral administration of risdiplam (0, 0.3, 1, or 3 mg/kg/day) resulted in increased incidences of preputial gland squamous cell carcinomas in males and combined thyroid follicular cell adenomas and carcinomas in females at the highest dose tested. The higher dose not associated with an increase in tumors (1 mg/kg/day) was associated with plasma drug exposures (AUC) similar to that in humans at the maximum recommended human dose (MRHD) of 5 mg/day.

The efficacy of EVRYSDI for the treatment of patients with infantile-onset, later-onset, and pre-symptomatic SMA was evaluated in three clinical studies, Study 1 (NCT02913482) and Study 2 (NCT02908685), and Study 3 (NCT03779334), respectively.

The overall findings of these studies support the effectiveness of EVRYSDI in SMA pediatric and adult patients and appear to support the early initiation of treatment with EVRYSDI.

Each amber glass bottle of EVRYSDI for oral solution is packaged with a bottle adapter, two 1 mL reusable oral syringes, two 6 mL reusable oral syringes, and one 12 mL reusable oral syringe. EVRYSDI for oral solution is a light yellow, pale yellow, yellow, greyish yellow, greenish yellow, or light green powder. Each bottle contains 60 mg of risdiplam (NDC 50242-175-07).

Please read and understand this

INSTRUCTIONS FOR USE

EVRYSDI^®[ev-RIZ-dee]

(risdiplam)

for oral solution

Please read and understand this

Instructions for Use

and thePatient Informationleaflet 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 (seeFigure A):

	1 Cap	Figure A
	1 Bottle adapter
	1 EVRYSDI bottle
	1 or 2 Reusable oral syringe(s)
	1Instructions for Use(not shown)
	1 Prescribing Information andPatient Information(not shown)
Reusable Oral Syringe Overview (seeFigure 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 with or without 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. If necessary, EVRYSDI can be kept at room temperature up to 104°F (up to 40°C) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not be more than 5 days. Throw away EVRYSDI if it has been kept at room temperature for more than 5 days. 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 mixed by the pharmacist (constitution) when stored in the refrigerator at 36°F to 46°F (2°C to 8°C). Please see the Discard After date written on the bottle label (seeFigure C). Ask your pharmacist for the Discard After date if it is not written on the bottle label. Throw away any unused portion of EVRYSDI that has been kept above 104°F (40°C). Keep EVRYSDI, 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) (SeeFigure 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 (SeeFigure 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 (SeeFigure F).
Figure G	Step A4 Carefully turn the bottle upside down with the syringe tip firmly inserted into the bottle adapter (SeeFigure 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 (SeeFigure 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 (SeeFigure 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 (SeeFigure 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 withStep A2.
Figure K	Step A8 Put the cap back on the bottle. Turn the cap to the right (clockwise) to tightly close the bottle (SeeFigure 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 (SeeFigure 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 (SeeFigure M).
Figure N	Step B3 Drink about a tablespoon (15 mL) of water right after taking the prescribed dose of EVRYSDI to make sure the drug has been completely swallowed (SeeFigure N). Go toStep Efor 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 (SeeFigure O).
Figure P	Step C2 Check that there is no EVRYSDI left in the oral syringe (SeeFigure 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 (SeeFigure Q). Go toStep Efor 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 (SeeFigure R).
Figure S	Step D2 Check that there is no EVRYSDI left in the oral syringe (SeeFigure 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 (SeeFigure T). Go toStep Efor 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 (SeeFigure U).
Figure V	Step E2 Rinse the plunger well under clean water (SeeFigure 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 (SeeFigure 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.

EVRYSDI is a registered trademark of Genentech, Inc.

Distributed by:

Genentech, Inc.

1 DNA Way

South San Francisco, CA 94080-4990

Approved: 2/2025

ThisInstructions for Usehas been Approved by the U.S. Food and Drug Administration.

©2025 Genentech, Inc. All Rights Reserved

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.

Each EVRYSDI carton contains (see

):

	1 Cap	Figure A
	1 Bottle adapter
	1 EVRYSDI bottle
	1 or 2 Reusable oral syringe(s)
	1 INSTRUCTIONS FOR USE EVRYSDI®[ev-RIZ-dee] (risdiplam) for oral solution Please read and understand this Instructions for Use and thePatient Informationleaflet 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 (seeFigure A): 1 Cap Figure A 1 Bottle adapter 1 EVRYSDI bottle 1 or 2 Reusable oral syringe(s) 1Instructions for Use(not shown) 1 Prescribing Information andPatient Information(not shown) Reusable Oral Syringe Overview (seeFigure 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 with or without 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. If necessary, EVRYSDI can be kept at room temperature up to 104°F (up to 40°C) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not be more than 5 days. Throw away EVRYSDI if it has been kept at room temperature for more than 5 days. 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 mixed by the pharmacist (constitution) when stored in the refrigerator at 36°F to 46°F (2°C to 8°C). Please see the Discard After date written on the bottle label (seeFigure C). Ask your pharmacist for the Discard After date if it is not written on the bottle label. Throw away any unused portion of EVRYSDI that has been kept above 104°F (40°C). Keep EVRYSDI, 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) (SeeFigure 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 (SeeFigure 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 (SeeFigure F). Figure G Step A4 Carefully turn the bottle upside down with the syringe tip firmly inserted into the bottle adapter (SeeFigure 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 (SeeFigure 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 (SeeFigure 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 (SeeFigure 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 withStep A2. Figure K Step A8 Put the cap back on the bottle. Turn the cap to the right (clockwise) to tightly close the bottle (SeeFigure 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 (SeeFigure 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 (SeeFigure M). Figure N Step B3 Drink about a tablespoon (15 mL) of water right after taking the prescribed dose of EVRYSDI to make sure the drug has been completely swallowed (SeeFigure N). Go toStep Efor 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 (SeeFigure O). Figure P Step C2 Check that there is no EVRYSDI left in the oral syringe (SeeFigure 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 (SeeFigure Q). Go toStep Efor 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 (SeeFigure R). Figure S Step D2 Check that there is no EVRYSDI left in the oral syringe (SeeFigure 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 (SeeFigure T). Go toStep Efor 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 (SeeFigure U). Figure V Step E2 Rinse the plunger well under clean water (SeeFigure 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 (SeeFigure 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. EVRYSDI is a registered trademark of Genentech, Inc. Distributed by: Genentech, Inc. 1 DNA Way South San Francisco, CA 94080-4990 Approved: 2/2025 ThisInstructions for Usehas been Approved by the U.S. Food and Drug Administration. ©2025 Genentech, Inc. All Rights Reserved (not shown)
	1 Prescribing Information and ThisPatient Informationhas been approved by the U.S. Food and Drug Administration. Issued: 2/2025 Patient Information EVRYSDI®[ev-RIZ-dee] (risdiplam) for oral solution EVRYSDI®[ev-RIZ-dee] (risdiplam) tablets What is EVRYSDI? EVRYSDI is a prescription medicine used to treat spinal muscular atrophy (SMA) in children and adults. Before taking EVRYSDI, tell your healthcare provider about all of your medical conditions, including if you: 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. Pregnancy Registry. There is a pregnancy registry for women who take EVRYSDI during pregnancy. The purpose of this registry is to collect information about the health of the pregnant woman and her baby. If you are pregnant or become pregnant while receiving EVRYSDI, tell your healthcare provider right away. Talk to your healthcare provider about registering with the EVRYSDI Pregnancy Registry. Your healthcare provider can enroll you in this registry or you can enroll by calling 1-833-760-1098 or visiting https://www.evrysdipregnancyregistry.com. 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, including your pharmacist, when you get a new medicine. How should I take EVRYSDI? 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. Your healthcare provider will either prescribe: EVRYSDI for oral solution Or EVRYSDI tablet 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. Take EVRYSDI exactly as your healthcare provider tells you to take it. Do not change the dose without talking to your healthcare provider. Avoid getting EVRYSDI on your skin or in your eyes. If it gets on your skin, wash the area with soap and water. If it gets in your eyes, rinse your eyes with water. If you are taking EVRYSDI for oral solution: see the detailedInstructions for Usethat comes with it for information on how to take or give EVRYSDI for 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 or other healthcare provider. If the medicine in the bottle is a powder, do not use it . Contact your pharmacist for a replacement. Take EVRYSDI one time daily with or without a meal at about the same time each day. Drink water afterwards to make sure EVRYSDI has been completely swallowed. In infants who are breastfed, EVRYSDI can be given before or after breastfeeding. Do not mix EVRYSDI with formula or milk. If you are unable to swallow and have a nasogastric (NG-tube) or gastrostomy tube (G-tube), EVRYSDI for oral solution can be given through the tube. Reusable Oral Syringes for EVRYSDI for Oral Solution Your pharmacist will provide you with the reusable oral syringes that are needed for taking your medicine and explain how to use them. You should receive 1 or 2 identical oral syringes depending on your prescribed daily dose. From the bottle, draw up (measure) the dose of EVRYSDI with these syringes, as they are made to protect the medicine from light. Take EVRYSDI right away after it has been drawn into the syringe. Do not store the EVRYSDI solution in the syringe. If EVRYSDI is not taken within 5 minutes of when it is drawn up, throw away the solution by pressing the plunger and prepare a new dose with the same syringe. Do not throw the syringes away because they are reusable. Wash the syringes per instructions after use. Contact your healthcare provider or pharmacist if your oral syringes are lost or damaged. If you are taking EVRYSDI Tablets: Take EVRYSDI one time daily with or without a meal at about the same time each day. Do not chew, cut, or crush the tablet. Swallow the EVRYSDI tablet whole with some water. Or You can take an EVRYSDI tablet by mouth after it is mixed with a teaspoon (5 mL) of room temperature non-chlorinated drinking water (e.g., filtered water). See the instructions below for taking EVRYSDI this way. EVRYSDI Tablets Mixed with Non-chlorinated Drinking Water (e.g., Filtered Water) Wash your hands before and after preparing or taking EVRYSDI tablets. Put EVRYSDI tablets in a small cup with a teaspoon (5 mL) of room temperature non-chlorinated drinking water (e.g., filtered water). Do not mix EVRYSDI tablets with any liquids other than non-chlorinated drinking water. Do not expose the EVRYSDI tablet mixture to sunlight. Swirl the cup gently until the tablet and non-chlorinated drinking water are fully mixed (though some particles may remain). This may take up to 3 minutes. Take EVRYSDI tablet mixture right away after mixing with non-chlorinated drinking water. If you do not take it within 10 minutes of adding non-chlorinated drinking water, throw the mixture away and make a new dose. After taking EVRYSDI tablet mixture, to make sure there is no medicine left, refill the small cup with at least a tablespoon (15 mL) of non-chlorinated drinking water, swirl, and take right away. If the EVRYSDI tablet mixture is spilled, use a dry paper towel to dry the area and then clean with soap and water. Throw the paper towel away in the trash and wash your hands with soap and water. Do not give the EVRYSDI tablet mixture via a nasogastric (NG-tube) or gastrostomy tube (G-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 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. 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, and sore throat (upper respiratory infection) lung infection (lower respiratory infection) constipation vomiting cough 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. How should I store EVRYSDI? EVRYSDI for Oral Solution: Store EVRYSDI in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze. If necessary, EVRYSDI can be kept at room temperature up to 104°F (up to 40°C) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not be more than 5 days. 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) or if EVRYSDI has been kept at room temperature (below 104°F [40°C]) for more than a total combined time of 5 days. Discard EVRYSDI if it has been kept above 104°F (40°C). Please see the Discard After date written on the bottle label. (See the Instructions for Use that comes with EVRYSDI for oral solution). EVRYSDI Tablets: Store at room temperature between 68°F to 77°F (20°C to 25°C). Keep the bottle tightly closed in order to protect from moisture. Keep EVRYSDI, all medicines and syringes out of the reach of children. General information about the safe and effective use of EVRYSDI. Medicines are sometimes prescribed for purposes other than those listed in aPatient Informationleaflet. 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. What are the ingredients in EVRYSDI? Active ingredient: risdiplam Inactive ingredients: EVRYSDI for Oral Solution: ascorbic acid, disodium edetate dihydrate, isomalt, mannitol, polyethylene glycol 6000, sodium benzoate, strawberry flavor, sucralose, and tartaric acid. EVRYSDI Tablets: colloidal silicon dioxide, crospovidone, mannitol, microcrystalline cellulose, polyethylene glycol 3350, polyvinyl alcohol, sodium stearyl fumarate, strawberry flavor, talc, tartaric acid, titanium dioxide, and yellow iron oxide. Distributed by: Genentech, Inc. , A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990 EVRYSDI is a registered trademark of Genentech, Inc. ©2025 Genentech, Inc. All rights reserved. For more information, go to www.EVRYSDI.com or call 1-833-387-9734. (not shown)
Reusable Oral Syringe Overview (see )		Figure B

• 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 with or without 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.

Store EVRYSDI in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze. If necessary, EVRYSDI can be kept at room temperature up to 104°F (up to 40°C) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not be more than 5 days. Throw away EVRYSDI if it has been kept at room temperature for more than 5 days. 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 mixed by the pharmacist (constitution) when stored in the refrigerator at 36°F to 46°F (2°C to 8°C). Please see the Discard After date written on the bottle label (see ). Ask your pharmacist for the Discard After date if it is not written on the bottle label. Throw away any unused portion of EVRYSDI that has been kept above 104°F (40°C). Keep EVRYSDI, all medicines and syringes out of the reach of children.

Figure C

Figure D	Step A1 Remove the cap by pushing it down and then twisting the cap to the left (counterclockwise) (See ). 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 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 G	Step A4 Carefully turn the bottle upside down with the syringe tip firmly inserted into the bottle adapter (See ).
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 ). 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 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 ) 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 ). Do not remove the bottle adapter from the bottle.

If you are taking your dose of EVRYSDI by mouth, follow the instructions in "

If you are taking your dose of EVRYSDI through a gastrostomy tube, follow the instructions in "

If you are taking your dose of EVRYSDI through a nasogastric tube, follow the instructions in "

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 ). 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 N	Step B3 Drink about a tablespoon (15 mL) of water right after taking the prescribed dose of EVRYSDI to make sure the drug has been completely swallowed (See ). Go to E) How to clean the oral syringe after use for cleaning of the syringe.

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 P	Step C2 Check that there is no EVRYSDI left in the oral syringe (See ).
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 ). Go to E) How to clean the oral syringe after use for cleaning of the syringe.

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 S	Step D2 Check that there is no EVRYSDI left in the oral syringe (See ).
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 ). Go to E) How to clean the oral syringe after use for cleaning of the syringe.

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 V	Step E2 Rinse the plunger well under clean water (See ).
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 ). 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.

EVRYSDI is a registered trademark of Genentech, Inc.

Distributed by:

INSTRUCTIONS FOR USE

EVRYSDI^®[ev-RIZ-dee]

(risdiplam)

for oral solution

Please read and understand this

Instructions for Use

and thePatient Informationleaflet 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 (seeFigure A):

	1 Cap	Figure A
	1 Bottle adapter
	1 EVRYSDI bottle
	1 or 2 Reusable oral syringe(s)
	1Instructions for Use(not shown)
	1 Prescribing Information andPatient Information(not shown)
Reusable Oral Syringe Overview (seeFigure 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 with or without 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. If necessary, EVRYSDI can be kept at room temperature up to 104°F (up to 40°C) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not be more than 5 days. Throw away EVRYSDI if it has been kept at room temperature for more than 5 days. 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 mixed by the pharmacist (constitution) when stored in the refrigerator at 36°F to 46°F (2°C to 8°C). Please see the Discard After date written on the bottle label (seeFigure C). Ask your pharmacist for the Discard After date if it is not written on the bottle label. Throw away any unused portion of EVRYSDI that has been kept above 104°F (40°C). Keep EVRYSDI, 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) (SeeFigure 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 (SeeFigure 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 (SeeFigure F).
Figure G	Step A4 Carefully turn the bottle upside down with the syringe tip firmly inserted into the bottle adapter (SeeFigure 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 (SeeFigure 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 (SeeFigure 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 (SeeFigure 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 withStep A2.
Figure K	Step A8 Put the cap back on the bottle. Turn the cap to the right (clockwise) to tightly close the bottle (SeeFigure 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 (SeeFigure 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 (SeeFigure M).
Figure N	Step B3 Drink about a tablespoon (15 mL) of water right after taking the prescribed dose of EVRYSDI to make sure the drug has been completely swallowed (SeeFigure N). Go toStep Efor 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 (SeeFigure O).
Figure P	Step C2 Check that there is no EVRYSDI left in the oral syringe (SeeFigure 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 (SeeFigure Q). Go toStep Efor 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 (SeeFigure R).
Figure S	Step D2 Check that there is no EVRYSDI left in the oral syringe (SeeFigure 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 (SeeFigure T). Go toStep Efor 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 (SeeFigure U).
Figure V	Step E2 Rinse the plunger well under clean water (SeeFigure 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 (SeeFigure 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.

EVRYSDI is a registered trademark of Genentech, Inc.

Distributed by:

Genentech, Inc.

1 DNA Way

South San Francisco, CA 94080-4990

Approved: 2/2025

ThisInstructions for Usehas been Approved by the U.S. Food and Drug Administration.

©2025 Genentech, Inc. All Rights Reserved

©2025 Genentech, Inc. All Rights Reserved

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.