Evrysdi

Risdiplam · Powder, For Solution · Oral

Prescription (Rx) Survival of Motor Neuron 2 Splicing Modifier

Uses

1 INDICATIONS AND USAGE EVRYSDI is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. EVRYSDI is a survival of motor neuron 2 (SMN2) splicing modifier indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. ( 1 )

Dosage and administration

Administer once daily with or without food per the table below ( 2.1 ): 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 ) Administer EVRYSDI for oral solution with the provided oral syringe. ( 2.2 ) EVRYSDI for oral solution must be constituted by a healthcare provider prior to dispensing. ( 2.4 ) See Full Prescribing Information for important preparation and administration instructions. ( 2.2 , 2.4 ) 2.1 Dosing Information EVRYSDI is administered orally once daily with or without food at approximately the same time each day. The recommended dosage is determined by age and body weight (see Table 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 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 [see Instructions for Use for EVRYSDI for Oral Solution and EVRYSDI Tablets and Patient Information ]. 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. EVRYSDI for oral solution can be administered via a nasogastric or gastrostomy tube. The tube should be flushed with water after delivering EVRYSDI for oral solution [see Instructions for Use ]. EVRYSDI Tablets Swallow EVRYSDI tablets whole with water. Do not chew, cut, or crush the tablets. Alternatively, 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. The dispersed EVRYSDI tablet can be administered via a nasogastric or gastrostomy tube that is 8 French or higher. Flush the tube with the non-chlorinated drinking water [at least one tablespoon (15 mL)] used to rinse the dispersion cup [see Instructions for Use ]. 2.3 Missed Dose If a dose of EVRYSDI is missed, EVRYSDI should be administered as soon as possible if still within 6 hours of the missed dose, and the usual dosing schedule can be resumed on the next day. Otherwise, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time on the next day. If a dose is not fully swallowed or vomiting occurs after taking a dose of EVRYSDI, another dose should not be administered to make up for the lost dose. The patient should wait until the next day to take the next dose at the regularly scheduled time. 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 [see Instructions 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.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS 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. For Oral Solution: 60 mg of risdiplam as a powder for constitution to provide 0.75 mg/mL solution. ( 3 ) Tablets: 5 mg

Contraindications

None. None. ( 4 )

Side effects

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. ( 6.1 ) 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials including patients with infantile-onset SMA, later-onset SMA, and pre-symptomatic SMA, a total of 491 patients (51% female, 74% Caucasian) were exposed to EVRYSDI for up to a median duration of 48.1 months (range: 0.6 to 63.4 months), with 231 patients receiving treatment for more than 24 months. At the time of first EVRYSDI dose, 90 (18%) patients were 18 years and older, 119 (24%) were 12 years to less than 18 years, 189 (39%) were 2 years to less than 12 years, 67 (14%) 2 months to less than 2 years, and 26 (5%) were less than 2 months. Clinical Trial in Later-Onset SMA The safety of EVRYSDI for later-onset SMA is based on data from a randomized, double-blinded, placebo-controlled study (Study 2 Part 2) in patients with SMA Type 2 or 3 (n = 180) [see Clinical Studies (14.2) ]. The patient population in Study 2 Part 2 ranged in age from 2 to 25 years at the time of the first dose. The most common adverse reactions (reported in at least 10% of patients treated with EVRYSDI and at an incidence greater than on placebo) in Study 2 Part 2 were fever, diarrhea, and rash. Table 2 lists the adverse reactions that occurred in at least 5% of patients treated with EVRYSDI and at an incidence ≥ 5% greater than on placebo in Study 2 Part 2. Table 2 Adverse Reactions Reported in ≥ 5% of Patients Treated with EVRYSDI and with an Incidence ≥ 5% Greater Than on Placebo in Study 2 Part 2 Adverse Reaction EVRYSDI (N = 120) % Placebo (N = 60) % Fever Includes pyrexia and hyperpyrexia. 22 17 Diarrhea 17 8 Rash Includes rash, erythema, rash maculo-papular, rash erythematous, rash papular, dermatitis allergic, and folliculitis. 17 2 Mouth and aphthous ulcers 7 0 Arthralgia 5 0 Urinary tract infection Includes urinary tract infection and cystitis. 5 0 Clinical Trial in Infantile-Onset SMA The safety of EVRYSDI therapy for infantile-onset SMA is based on data from an open-label study in 62 patients (Study 1) [see Clinical Studies (14.1) ]. The patient population ranged in age from 2 to 7 months at the time of the first EVRYSDI dose (weight range: 4.1 to 10.6 kg). The most frequent adverse reactions reported in infantile-onset SMA patients treated with EVRYSDI in Study 1 were similar to those observed in later-onset SMA patients in Study 2. Additionally, the following adverse reactions reported in ≥ 10% of patients were: upper respiratory tract infection (including nasopharyngitis, rhinitis), lower respiratory tract infection (including pneumonia, bronchitis), constipation, vomiting, and cough. Clinical Trial in Pre-Symptomatic SMA The safety of EVRYSDI therapy for pre-symptomatic SMA is based on data from an open-label, single-arm study in 26 patients (Study 3) [see Clinical Studies (14.3) ] . The patient population ranged in age from 16 to 41 days at the time of the first dose (weight range: 3.1 to 5.7 kg). The safety profile of EVRYSDI in pre-symptomatic patients in Study 3 is consistent with the safety profile for symptomatic SMA patients treated with EVRYSDI in clinical trials.

Drug interactions

Avoid coadministration with drugs that are substrates of multidrug and toxin extrusion (MATE) transporters. ( 7.1 ) 7.1 Effect of EVRYSDI on Substrates of Multidrug and Toxin Extrusion (MATE) Protein Transporters Based on in vitro data, EVRYSDI may increase plasma concentrations of drugs eliminated via MATE1 or MATE2-K [see Clinical Pharmacology (12.3) ] , such as metformin. Avoid coadministration of EVRYSDI with MATE substrates. If coadministration cannot be avoided, monitor for drug-related toxicities and consider dosage reduction of the coadministered drug (based on the labeling of that drug) if needed.

Use in specific populations

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to EVRYSDI during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-760-1098 or visiting https://www.evrysdipregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of EVRYSDI in pregnant women. In animal studies, administration of risdiplam during pregnancy or throughout pregnancy and lactation resulted in adverse effects on development (embryofetal mortality, malformations, decreased fetal body weights, and reproductive impairment in offspring) at or above clinically relevant drug exposures [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Based on animal data, advise pregnant women of the potential risk to the fetus. Data Animal Data Oral administration of risdiplam (0, 1, 3, or 7.5 mg/kg/day) to pregnant rats throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal structural variations at the highest dose tested, which was not associated with maternal toxicity. The no-effect level for adverse effects on embryofetal development (3 mg/kg/day) was associated with maternal plasma exposure (AUC) approximately 2 times that in humans at the maximum recommended human dose (MRHD) of 5 mg. Oral administration of risdiplam (0, 1, 4, or 12 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in embryofetal mortality, fetal malformations (hydrocephaly), and structural variations at the highest dose tested, which was associated with maternal toxicity. The no-effect dose for adverse effects on embryofetal development (4 mg/kg/day) was associated with maternal plasma exposure (AUC) approximately 4 times that in humans at the MRHD. When risdiplam (0, 0.75, 1.5, or 3 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, gestation was prolonged in the dams, and delayed sexual maturation (vaginal opening) and impaired reproductive function (decreased numbers of corpora lutea, implantation sites, and live embryos) were observed in female offspring at the highest dose. The no-effect dose for adverse effects on pre- and postnatal development in rats (1.5 mg/kg/day) was associated with maternal plasma exposure (AUC) similar to that in humans at the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of risdiplam in human milk, the effects on the breastfed infant, or the effects on milk production. Risdiplam was excreted in the milk of lactating rats orally administered risdiplam. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for EVRYSDI and any potential adverse effects on the breastfed infant from EVRYSDI or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Studies of risdiplam in juvenile and adult rats and in monkeys demonstrated adverse effects on the reproductive organs, including germ cells, in males at clinically relevant plasma exposures [see Use in Specific Populations (8.4) and Nonclinical Toxicology (13.1) ] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiating EVRYSDI [see Use in Specific Populations (8.1) ] . Contraception EVRYSDI may cause embryofetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Female Patients Advise female patients of reproductive potential to use effective contraception during treatment with EVRYSDI and for at least 1 month after her last dose. Infertility Male Patients Male fertility may be compromised by treatment with EVRYSDI [see Nonclinical Toxicology (13.1) ] . Counsel male patients of reproductive potential receiving EVRYSDI about the potential effects on fertility. Male patients may consider sperm preservation prior to treatment. 8.4 Pediatric Use The safety and effectiveness of EVRYSDI in pediatric patients (neonates and older) have been established . Use of EVRYSDI for SMA is supported by evidence from adequate and well-controlled studies of EVRYSDI in patients 2 months of age and older with SMA. Use of EVRYSDI for SMA in patients 2 months of age and younger is supported by pharmacokinetic and safety data from pediatric patients 16 days and older, and pharmacokinetic modeling and simulation to identify the dosing regimen [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . Juvenile Animal Toxicity Data Oral administration of risdiplam (0, 0.75, 1.5, 2.5 mg/kg/day) to young rats from postnatal day (PND) 4 through PND 31 resulted in decreased growth (body weight, tibia length) and delayed sexual maturation in males at the mid and high dose. The skeletal and body weight deficits persisted after cessation of dosing. Ophthalmic changes consisting of vacuoles in the anterior vitreous were seen at the high dose. Decreases in absolute B lymphocyte counts were observed at all doses after cessation of dosing. Decreases in testis and epididymis weights, which correlated with degeneration of the seminiferous epithelium in the testis, occurred at the mid and high doses; the histopathology findings were reversible, but organ weight persisted after cessation of dosing. Impaired female reproductive performance (decreased mating index, fertility index, and conception rate) was observed at the high dose. A no-effect dose for adverse developmental effects on preweaning rats was not identified.

Pregnancy

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to EVRYSDI during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-760-1098 or visiting https://www.evrysdipregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of EVRYSDI in pregnant women. In animal studies, administration of risdiplam during pregnancy or throughout pregnancy and lactation resulted in adverse effects on development (embryofetal mortality, malformations, decreased fetal body weights, and reproductive impairment in offspring) at or above clinically relevant drug exposures [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Based on animal data, advise pregnant women of the potential risk to the fetus. Data Animal Data Oral administration of risdiplam (0, 1, 3, or 7.5 mg/kg/day) to pregnant rats throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal structural variations at the highest dose tested, which was not associated with maternal toxicity. The no-effect level for adverse effects on embryofetal development (3 mg/kg/day) was associated with maternal plasma exposure (AUC) approximately 2 times that in humans at the maximum recommended human dose (MRHD) of 5 mg. Oral administration of risdiplam (0, 1, 4, or 12 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in embryofetal mortality, fetal malformations (hydrocephaly), and structural variations at the highest dose tested, which was associated with maternal toxicity. The no-effect dose for adverse effects on embryofetal development (4 mg/kg/day) was associated with maternal plasma exposure (AUC) approximately 4 times that in humans at the MRHD. When risdiplam (0, 0.75, 1.5, or 3 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, gestation was prolonged in the dams, and delayed sexual maturation (vaginal opening) and impaired reproductive function (decreased numbers of corpora lutea, implantation sites, and live embryos) were observed in female offspring at the highest dose. The no-effect dose for adverse effects on pre- and postnatal development in rats (1.5 mg/kg/day) was associated with maternal plasma exposure (AUC) similar to that in humans at the MRHD.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of EVRYSDI in pediatric patients (neonates and older) have been established . Use of EVRYSDI for SMA is supported by evidence from adequate and well-controlled studies of EVRYSDI in patients 2 months of age and older with SMA. Use of EVRYSDI for SMA in patients 2 months of age and younger is supported by pharmacokinetic and safety data from pediatric patients 16 days and older, and pharmacokinetic modeling and simulation to identify the dosing regimen [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . Juvenile Animal Toxicity Data Oral administration of risdiplam (0, 0.75, 1.5, 2.5 mg/kg/day) to young rats from postnatal day (PND) 4 through PND 31 resulted in decreased growth (body weight, tibia length) and delayed sexual maturation in males at the mid and high dose. The skeletal and body weight deficits persisted after cessation of dosing. Ophthalmic changes consisting of vacuoles in the anterior vitreous were seen at the high dose. Decreases in absolute B lymphocyte counts were observed at all doses after cessation of dosing. Decreases in testis and epididymis weights, which correlated with degeneration of the seminiferous epithelium in the testis, occurred at the mid and high doses; the histopathology findings were reversible, but organ weight persisted after cessation of dosing. Impaired female reproductive performance (decreased mating index, fertility index, and conception rate) was observed at the high dose. A no-effect dose for adverse developmental effects on preweaning rats was not identified. The lowest dose tested (0.75 mg/kg/day) was associated with plasma exposures (AUC) lower than that in humans at the maximum recommended human dose (MRHD) of 5 mg/day. Oral administration of risdiplam (0, 1, 3, or 7.5 mg/kg/day) to young rats from PND 22 through PND 112 produced a marked increase in micronuclei in the bone marrow, male reproductive organ histopathology (degeneration/necrosis of the seminiferous tubule epithelium, oligo/aspermia in the epididymis, spermatic granulomas), and adverse effects on sperm parameters (decreased sperm concentration and motility, increased sperm morphology abnormalities) at the highest dose tested. Increases in T lymphocytes (total, helper, and cytotoxic) were observed at the mid and high doses. The reproductive and immune effects persisted after cessation of dosing. The no-effect dose (1 mg/kg/day) for adverse effects on postweaning juvenile rats was associated with plasma exposures (AUC) lower than that in humans at the MRHD.

Geriatric use

8.5 Geriatric Use Clinical studies of EVRYSDI did not include patients aged 65 years and older to determine whether they respond differently from younger adult patients.

Description

11 DESCRIPTION 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 pKa 1 of 3.78 (base) and pKa 2 of 6.62 (base). The molecular formula of risdiplam is C 22 H 23 N 7 O 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 [see Dosage and Administration (2.4) ]. 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. Chemical Structure

Mechanism of action

12.1 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 supplied

16.1 EVRYSDI for Oral Solution How Supplied 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). Storage and Handling Store the dry powder at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature] . Keep in the original carton. 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) [see Dosage and Administration (2.4) ]. 16.2 EVRYSDI Tablets How Supplied Pale yellow film-coated tablet, round and curved, with EVR debossed on one side; available in HDPE bottles of 30 tablets with a child-resistant cap (NDC 50242-202-01). Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Keep in the original bottle. Keep the bottle tightly closed in order to protect from moisture.

Storage

Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Keep in the original bottle. Keep the bottle tightly closed in order to protect from moisture.

Patient information

Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Pregnancy and Fetal Risk Inform pregnant women and women of reproductive potential that, based on animal studies, EVRYSDI may cause fetal harm [see Use in Specific Populations (8.1) ]. Discuss with women of childbearing age whether they are pregnant, might be pregnant, or are trying to become pregnant. Advise women of childbearing potential to use effective contraception during treatment with EVRYSDI and for at least 1 month after stopping EVRYSDI. Advise a female patient to immediately inform the prescriber if she is pregnant or planning to become pregnant [see Use in Specific Populations (8.3) ]. Pregnancy Registry Encourage patients to enroll in the EVRYSDI Pregnancy Registry if they become pregnant while taking EVRYSDI [see Use in Specific Populations (8.1) ] . Potential Effects on Male Fertility Advise male patients that their fertility may be compromised while on treatment with EVRYSDI [see Use in Specific Populations (8.3) ]. Instructions for Preparation of Oral Solution Advise patients/caregivers to ensure that EVRYSDI oral solution is in liquid form when received from the pharmacy. Instruct patients/caregivers to take EVRYSDI oral solution with or without food or before or after breastfeeding at approximately the same time each day. However, instruct caregivers not to mix EVRYSDI with formula or milk. Instruct patients/caregivers to take EVRYSDI oral solution immediately after it is drawn up into the reusable oral syringe [see Dosage and Administration (2.2) ]. Instructions for EVRYSDI Tablets Advise patients/caregivers to swallow EVRYSDI tablets whole with water. Do not chew, cut, or crush the tablets. Alternatively, the tablet can be dispersed in one teaspoon (5 mL) of room temperature non-chlorinated drinking water (e.g., filtered water) and taken immediately. EVRYSDI tablets must not be dispersed in any liquid other than non-chlorinated drinking water. Instruct the patient/caregivers that the dispersion must be administered within 10 minutes of adding non-chlorinated drinking water, or it must be discarded [see Dosage and Administration (2.2) ] . Advise patients/caregivers to wash their hands before and after preparing or taking EVRYSDI tablets. Advise patients/caregivers to avoid getting the dispersed tablet on their skin or in their eyes. Advise patients/caregivers to wash the area with soap and water if the dispersed tablet gets on the skin. Advise patients/caregivers to rinse their eyes with water if the dispersed tablet gets in the eyes. Advise patients/caregivers to use a dry paper towel to dry the area if the dispersion is spilled and then clean with soap and water. Advise patients/caregivers to throw the paper towel away in the trash and wash their hands with soap and water.

Label text from the FDA structured product label by Genentech, Inc. (revised Feb 19, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Risdiplam in 2 products

Evrysdi NDC products (2)

NDC	Strength & form	Labeler	Type
50242-175	Risdiplam .75 mg/mL Powder, For Solution	Genentech, Inc.	NDA
50242-202	Risdiplam 5 mg/1 Tablet	Genentech, Inc.	NDA

Frequently asked questions

What is Evrysdi used for?

What are the side effects of Evrysdi?

Who makes Evrysdi?

Evrysdi is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..