Risdiplam
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
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Overview
Risdiplam is a enhancer of SMN2 gene transcription that is FDA approved for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.. Common adverse reactions include Fever Diarrhea Rash Mouth and Aphtous Ulcers Arthralgia UTI.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- EVRYSDI is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
DOSAGE:
- Less than 2 months of age: 0.15 mg/kg
- 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
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Risdiplam in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Risdiplam in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Risdiplam FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Risdiplam in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Risdiplam in pediatric patients.
Contraindications
None
Warnings
There is limited information regarding Risdiplam Warnings' in the drug label.
Adverse Reactions
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). 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.
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. 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. 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.
Postmarketing Experience
There is limited information regarding Risdiplam Postmarketing Experience in the drug label.
Drug Interactions
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
Pregnancy Category (FDA):
There is no FDA guidance on usage of Risdiplam in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Risdiplam in women who are pregnant.
Labor and Delivery
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.
Nursing Mothers
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.
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
Geriatic Use
Clinical studies of EVRYSDI did not include patients aged 65 years and older to determine whether they respond differently from younger adult patients.
Gender
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.
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential prior to initiating EVRYSDI.
Contraception
EVRYSDI may cause embryofetal harm when administered to a pregnant woman .
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.
Counsel male patients of reproductive potential receiving EVRYSDI about the potential effects on fertility. Male patients may consider sperm preservation prior to treatment.
Race
There is no FDA guidance on the use of Risdiplam with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Risdiplam in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Risdiplam in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Risdiplam in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Risdiplam in patients who are immunocompromised.
Administration and Monitoring
Administration
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.
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
Monitoring
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.
IV Compatibility
There is limited information regarding the compatibility of Risdiplam and IV administrations.
Overdosage
There is limited information regarding Risdiplam overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Risdiplam Pharmacology in the drug label.
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.
Structure
There is limited information regarding Risdiplam Structure in the drug label.
Pharmacodynamics
In clinical trials for infantile-onset SMA and later-onset SMA patients, EVRYSDI led to an increase in SMN protein with a greater than 2-fold median change from baseline within 4 weeks of treatment initiation across all SMA types studied. The increase was sustained throughout the treatment period (of at least 24 months).
Cardiac Electrophysiology
At the maximum recommended dose, clinically significant QTc interval prolongation was not observed.
Pharmacokinetics
Pharmacokinetics of EVRYSDI have been characterized in healthy adult subjects and in patients with SMA.
After administration of EVRYSDI as an oral solution, pharmacokinetics of risdiplam were approximately linear between 0.6 and 18 mg in a single-ascending-dose study in healthy adult subjects, and between 0.02 and 0.25 mg/kg once daily in a multiple-ascending-dose study in patients with SMA. Following once-daily oral administration of risdiplam in healthy subjects, approximately 3-fold accumulation of peak plasma concentrations (Cmax) and area under the plasma concentration-time curve (AUC0-24h) was observed. Risdiplam exposures reach steady state 7 to 14 days after once daily administration. EVRYSDI tablet (swallowed whole or dispersed in water) demonstrated comparable bioavailability to EVRYSDI for oral solution in adult healthy volunteers under fasted and fed states.
Absorption
Following oral administration of risdiplam in fasted state, the median time to reach maximum plasma concentration (Tmax) was 3.26 to 4 hours. The Tmax was delayed by up to1 hour in fed state compared to that under fasted state.
Effect of Food
Food (high-fat, high calorie breakfast) had no relevant effect on the exposure of risdiplam. In the clinical efficacy studies (Study 1 and Study 2), risdiplam was administered with a morning meal or after breastfeeding.
Distribution
The apparent volume of distribution at steady state is 190.4 L for a 31.3 kg patient.
Risdiplam is predominantly bound to serum albumin, without any binding to alpha-1 acid glycoprotein, with a free fraction of 11%.
Elimination
The apparent clearance (CL/F) of risdiplam is 2.45 L/h for a 31.3 kg patient.
The terminal elimination half-life of risdiplam was approximately 50 hours in healthy adults.
Metabolism
Risdiplam is primarily metabolized by flavin monooxygenase 1 and 3 (FMO1 and FMO3) and also by CYPs 1A1, 2J2, 3A4, and 3A7.
Parent drug was the major component found in plasma, accounting for 83% of drug-related material in circulation. The pharmacologically-inactive metabolite M1 was identified as the major circulating metabolite.
Excretion
Following a dose of 18 mg, approximately 53% of the dose (14% unchanged risdiplam) was excreted in the feces and 28% in urine (8% unchanged risdiplam).
Specific Populations
There were no clinically significant differences in the pharmacokinetics of EVRYSDI based on race or gender. Renal impairment is not expected to alter the exposures to risdiplam.
The impact of geriatric age on the pharmacokinetics of EVRYSDI has not been studied.
Hepatic Impairment
The pharmacokinetics and safety of risdiplam have been studied in subjects with mild or moderate hepatic impairment (as defined by Child-Pugh class A and B, respectively, n = 8 each) compared to subjects with normal hepatic function (n = 10). Following the administration of 5 mg EVRYSDI, the AUCinf and Cmax of risdiplam were approximately 20% and 5% lower, respectively, in subjects with mild hepatic impairment and were approximately 8% and 20% higher, respectively, in subjects with moderate hepatic impairment, versus matched healthy control subjects. The magnitude of these changes is not considered to be clinically meaningful. The pharmacokinetics and safety in patients with severe hepatic impairment (Child-Pugh class C) have not been studied.
Pediatric Patients
Body weight and age were found to have significant effect on the pharmacokinetics of risdiplam. The estimated exposure (mean AUC0-24h) in pre-symptomatic infants at the age of 1 to 2 months was 2090 ng.h/mL at the recommended dose of 0.15 mg/kg once daily. The estimated exposure for infantile-onset SMA patients (age 2 to 7 months at enrollment) at the recommended dose of 0.2 mg/kg once daily was 1930 ng.h/mL. The estimated exposure for later-onset SMA patients (2 to 25 years old at enrollment) at the recommended dose was 2070 ng.h/mL (0.25 mg/kg once daily for patients with a body weight < 20 kg and 5 mg once daily for patients with a body weight ≥ 20 kg).
No data on risdiplam pharmacokinetics are available in patients less than 16 days of age [see Use in Specific Populations (8.4)].
Drug Interaction Studies
Effect of Other Drugs on EVRYSDI
Coadministration of 200 mg itraconazole (a strong CYP3A inhibitor) twice daily with a single 6 mg oral dose of risdiplam did not have a clinically relevant effect on the pharmacokinetics of risdiplam (11% increase in AUC and 9% decrease in Cmax).
Risdiplam is a weak substrate of human MDR-1 and breast cancer resistant protein (BCRP) transporters in vitro. Human MDR-1 or BCRP inhibitors are not expected to result in a clinically significant increase of risdiplam concentrations.
Effect of EVRYSDI on Other Drugs
Risdiplam and its major circulating metabolite M1 did not induce CYP1A2, 2B6, 2C8, 2C9, 2C19, or 3A4 in vitro. Risdiplam and M1 did not inhibit (reversible or time-dependent inhibition) any of the CYP enzymes tested (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6), with the exception of CYP3A in vitro.
EVRYSDI is a weak inhibitor of CYP3A. In healthy adult subjects, administration of EVRYSDI once daily for 2 weeks slightly increased the exposure of midazolam, a sensitive CYP3A substrate (AUC 11%; Cmax 16%); this increase is not considered clinically relevant. Based on physiologically-based pharmacokinetic (PBPK) modeling, a similar increase is expected in children and infants as young as 2 months of age.
In vitro studies have shown that risdiplam and its major metabolite are not significant inhibitors of human MDR1, organic anion-transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter 1 and 3 (OAT 1 and 3) transporters, and human organic cation transporter 2 (OCT2), at clinically relevant concentrations. Risdiplam and its metabolite are, however, in vitro inhibitors of the multidrug and toxin extrusion (MATE) 1 and MATE2-K transporters.
Nonclinical Toxicology
Carcinogenesis
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.
Mutagenesis
Risdiplam was negative in an in vitro Ames assay. In an in vivo combined bone marrow micronucleus and comet assay in rat, risdiplam was clastogenic, as evidenced by an increase in micronuclei in bone marrow, but was negative in the comet assay. A pronounced increase in bone marrow micronuclei was also observed in toxicity studies in adult and juvenile rats.
Impairment of Fertility
Oral administration of risdiplam to rats for 4 (0, 1, 3, or 9 mg/kg/day) or 26 (0, 1, 3, or 7.5 mg/kg/day) weeks resulted in histopathological effects in the testis (degenerated spermatocytes, degeneration/atrophy of the seminiferous tubules) and epididymis (degeneration/necrosis of ductular epithelium) at the mid and/or high doses. At the high dose in the 26-week study, the testicular lesions persisted to the end of the recovery period, which corresponds, in rat, to approximately one spermatogenic cycle. The no-effect dose for adverse reproductive system effects in adult male rats (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.
Adverse effects of risdiplam on the testis could not be fully evaluated in the monkey because the majority of monkeys tested were sexually immature. However, oral administration of risdiplam (0, 2, 4, or 6 mg/kg/day) for 2 weeks resulted in histopathological changes in the testis (increases in multinucleate cells, germ cell degeneration) at the highest dose. At the no-effect dose for testicular toxicity in monkeys, plasma exposures were approximately 3 times that in humans at the MRHD.
Oral administration of risdiplam to postweaning juvenile rats resulted in male reproductive toxicity (degeneration/necrosis of the testis seminiferous epithelium with associated oligo/aspermia in the epididymis and abnormal sperm parameters). The no-effect dose for adverse reproductive effects in postweaning male juvenile rats was associated with plasma exposures approximately 4 times that in humans at the MRHD
Clinical Studies
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.
Infantile-Onset SMA Study 1 was an open-label, 2-part study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI for oral solution in patients with Type 1 SMA (symptom onset between 28 days and 3 months of age). All patients had genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the SMN1 gene, and two SMN2 gene copies.
Part 1 of Study 1 was designed as a dose-finding study. Part 2 of Study 1 assessed the safety and efficacy of EVRYSDI at 0.20 mg/kg, the recommended dose determined in Part 1. Patients from Part 1 did not take part in Part 2.
A total of 62 patients with symptomatic Type 1 SMA were enrolled in FIREFISH Part 1 (n = 21) and Part 2 (n = 41), of which 58 patients received the recommended dosage [see Dosage and Administration (2.1)]. The median age of onset of clinical signs and symptoms was 1.5 months (range: 0.9 to 3.0 months). The median age at enrollment was 5.6 months (range: 2.2 to 6.9 months), and the median time between onset of symptoms and the first dose was 3.7 months (range 1.0 to 6.0 months). Of these patients, 60% were female, 57% were Caucasian, and 29% were Asian. The demographics and baseline disease characteristics were comparable between Part 1 and Part 2 of the study.
Effectiveness was established based on the ability to sit without support for at least 5 seconds (as measured by Item 22 of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) gross motor scale) and on the basis of survival without permanent ventilation. Permanent ventilation was defined as requiring a tracheostomy or more than 21 consecutive days of either non-invasive ventilation (≥ 16 hours per day) or intubation, in the absence of an acute reversible event.
The primary endpoint was the proportion of patients with the ability to sit without support for at least 5 seconds (BSID-III gross motor scale, Item 22) after 12 months of treatment in Part 2; 29% of patients (n = 12/41) achieved this milestone.
Later Onset SMA Study 2 was a 2-part, multicenter trial to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI for oral solution in patients diagnosed with SMA Type 2 or Type 3. Part 1 of Study 2 was dose-finding and exploratory in 51 patients (14% ambulatory). Part 2 was randomized, double-blind, placebo-controlled, and is described below.
The primary endpoint in Study 2 Part 2 was the change from baseline to Month 12 in the Motor Function Measure 32 (MFM32) score. A key secondary endpoint was the proportion of patients with a 3-point or greater change from baseline to Month 12 in the MFM32 total score. The MFM32 measures motor function abilities that relate to daily functions. The total MFM32 score is expressed as a percentage (range: 0 to 100) of the maximum possible score, with higher scores indicating greater motor function. Another key secondary endpoint was the Revised Upper Limb Module (RULM). The RULM is a tool used to assess motor performance of the upper limb in SMA patients. It tests proximal and distal motor functions of the arm. The total score ranges from 0 (all the items cannot be performed) to 37 (all the activities are achieved fully without any compensatory maneuvers). Study 2 Part 2 enrolled 180 non-ambulatory patients with Type 2 (71%) or Type 3 (29%) SMA. Patients were randomized 2:1 to receive EVRYSDI at the recommended dosage or placebo. Randomization was stratified by age group (2 to 5, 6 to 11, 12 to 17, or 18 to 25 years of age). The median age of patients at the start of treatment was 9.0 years (range: 2 to 25), and the median time between onset of initial SMA symptoms and first treatment was 102.6 months (range: 1 to 275). Of the 180 patients included in the trial, 51% were female, 67% were Caucasian, and 19% were Asian. At baseline, 67% of patients had scoliosis (32% of them with severe scoliosis). Patients had a mean baseline MFM32 score of 46.1, and RULM score of 20.1. Overall baseline demographic characteristics were reasonably balanced between the treatment groups (EVRYSDI and placebo), with the exception of scoliosis (63% in the EVRYSDI arm vs. 73% in the placebo group).
The primary analysis on the change from baseline in MFM32 total score at Month 12 showed a clinically meaningful and statistically significant difference between patients treated with EVRYSDI and placebo.
Pre-Symptomatic SMA Study 3 was an open-label, single-arm, multicenter clinical study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI in infants up to 6 weeks of age (at first dose) who have been genetically diagnosed with SMA but do not yet present with symptoms.
The efficacy in pre-symptomatic SMA patients was evaluated at Month 12 in 26 patients treated with EVRYSDI in Study 3: 8 patients had 2 copies of the SMN2 gene, 13 patients had 3 copies, and 5 patients had 4 or more copies. The median age of these patients at first dose was 25 days (range: 16 to 41), 62% were female, and 85% were Caucasian. The primary efficacy population (N = 5) included patients with 2 SMN2 copies and a baseline CMAP amplitude ≥1.5 mV.
The primary efficacy endpoint was the proportion of patients with the ability to sit without support for at least 5 seconds (BSID-III gross motor scale, Item 22) at Month 12. This milestone was achieved by 80% (4/5) of patients in the primary efficacy population. This milestone was also achieved by 87.5% (7/8) of all patients with 2 copies of SMN2 and 96.2% (25/26) of patients in the full treated population.
At Month 12, 80.8% (21/26) of patients in the full treated population achieved sitting without support for 30 seconds (BSID-III, Item 26). Of the 26 patients treated with EVRYSDI, 25 patients had motor milestones measured by the HINE-2 at Month 12. Of these, 24 (96%) achieved sitting (23 patients could pivot/rotate and 1 achieved stable sit); 21 (84%) could stand (13 patients could stand unaided and 8 could stand with support); and 12 (48%) could walk independently. Seven patients were not tested for walking at Month 12. All 26 patients were alive at 12 months without permanent ventilation.
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).
EVRYSDI Tablets 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
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)
EVRYSDI Tablets 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 the bottle tightly closed in order to protect from moisture.
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Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling.
Pregnancy and Fetal Risk
Inform pregnant women and women of reproductive potential that, based on animal studies, EVRYSDI may cause fetal harm.
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.
Pregnancy Registry
Encourage patients to enroll in the EVRYSDI Pregnancy Registry if they become pregnant while taking EVRYSDI.
Potential Effects on Male Fertility
Advise male patients that their fertility may be compromised while on treatment with EVRYSDI.
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.
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.
Advise patients/caregivers that the EVRYSDI tablet dispersion is for oral administration only. If administration through a nasogastric/gastrostomy tube is required, EVRYSDI for oral solution should be used.
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.
Precautions with Alcohol
Alcohol-Risdiplam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
EVRYSDI
Look-Alike Drug Names
There is limited information regarding Risdiplam Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.