Risdiplam (Monograph)
Brand name: Evrysdi
Drug class: Other Miscellaneous Therapeutic Agents
Introduction
Small molecule survival motor neuron 2 (SMN2) splicing modifier.
Uses for Risdiplam
Spinal Muscular Atrophy
Used for treatment of spinal muscular atrophy (SMA) in adult and pediatric patients (including neonates).
Designated an orphan drug by FDA for treatment of SMA.
Guidelines from an international group of experts on SMA have been published. Early treatment is critical, especially for Type 1 disease, due to rapid motor neuron loss. Among currently available options, treatment of choice (nusinersen, onasemnogene abeparvovec, or risdiplam) should be guided by patient age, clinical status, and treatment access.
Risdiplam Dosage and Administration
General
Pretreatment Screening
-
Verify pregnancy status in female patients of reproductive potential.
Administration
Oral Administration
Administer orally once daily with or without food at approximately the same time each day.
Available as 5 mg oral tablets and as a 60 mg powder for oral solution that yields 0.75 mg/mL when constituted.
If dose is missed, administer missed dose within 6 hours; otherwise, skip and resume the next day. If the dose is not fully swallowed or vomiting occurs, do not repeat; wait for next scheduled dose.
Tablets
Swallow risdiplam tablets whole with water; do not chew, cut, or crush.
If needed, disperse in 5 mL of room temperature, non-chlorinated water only. Swirl up to 3 minutes and administer immediately. Rinse cup with 15 mL of the same water, swirl, and administer again. Use within 10 minutes or discard.
Powder for Oral Solution
Risdiplam oral solution must be prepared by a healthcare provider.
Use gloves and avoid inhalation or contact with skin or mucous membranes.
To prepare, tap the bottle, add 79 mL purified water, insert adapter, cap, shake for 15 seconds, wait 10 minutes, and shake again if not clear. Label with expiration date (64 days) and lot number, place in carton, and dispense with the correct syringe and Instructions for Use. Refer to manufacturer labeling for full instructions.
May administer oral solution before or after breastfeeding, but do not mix with milk or formula. Administer within 5 minutes of drawing into the reusable oral syringe provided by manufacturer; discard if delayed >5 minutes. Patients should drink water after dosing to ensure entire dose is swallowed.
Gastric or NG Tube Administration
For patients with nasogastric or gastrostomy tube, may administer risdiplam oral solution through the tube; flush with water after administration. Do not use tablets.
Dosage
Dosage based on patient's weight and age.
Pediatric Patients
Spinal Muscular Atrophy
Oral
<2 months of age: 0.15 mg/kg of oral solution once daily.
2 months to <2 years of age: 0.2 mg/kg of oral solution once daily.
≥2 years of age and <20 kg: 0.25 mg/kg of oral solution once daily.
≥2 years of age and >20 kg: 5 mg of oral solution or tablet once daily.
Adults
Spinal Muscular Atrophy
Oral
5 mg of oral solution or tablet once daily.
Special Populations
Hepatic Impairment
No specific dosage recommendations.
Renal Impairment
No specific dosage recommendations.
Geriatric Patients
No specific dosage recommendations.
Cautions for Risdiplam
Contraindications
-
None.
Warnings/Precautions
Specific Populations
Pregnancy
No adequate data in pregnant women. In animals, risdiplam caused fetal harm and long-term reproductive effects at clinically relevant exposures.
Clinicians are encouraged to register patients and pregnant women are encouraged to register themselves in a pregnancy exposure registry by calling 1-833-760-1098 or visiting [Web].
Lactation
No data on risdiplam in human milk, effects on breast-fed infant, or milk production. Distributed into rat milk. Weigh breastfeeding benefits against maternal need for drug and infant risk.
Females and Males of Reproductive Potential
Risdiplam may harm the fetus. Females should use contraception during treatment and for 1 month after therapy. Counsel males on possible fertility effects; risdiplam affected male reproductive organs in animals.
Pediatric Use
Safety and efficacy established, with use in patients ≥2 months of age supported by clinical trials; use in infants <2 months of age supported by pharmacokinetic and safety data from infants ≥16 days of age and dosing simulations.
Geriatric Use
Clinical studies did not include patients ≥65 years of age.
Hepatic Impairment
Risdiplam exposure slightly altered in mild/moderate liver impairment but not deemed clinically meaningful; not studied in severe impairment (Child-Pugh C).
Renal Impairment
Not expected to alter exposure.
Common Adverse Effects
In later-onset SMA, most common adverse effects (≥10%) were fever, diarrhea, rash. In infantile-onset SMA, similar adverse reactions observed, along with upper and lower respiratory tract infections, constipation, vomiting, cough.
Drug Interactions
Primarily metabolized by flavin monooxygenase (FMO) 1 and FMO4 and also by CYP1A1, 2J2, 3A4, and 3A7.
Drugs Affecting or Affected by Hepatic Microsomal Enzymes
Does not induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A4.
Weak inhibitor of CYP3A4.
Drugs Affecting or Affected by Transport Systems
Weak substrate of multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP).
Does not inhibit MDR1, organic anion-transporting polypeptides (OATP) 1B1 and 1B3, organic anion transporters (OAT) 1 and 3, or organic cation transporter (OCT) 2.
May increase plasma levels of multidrug and toxin extrusion (MATE) 1 or MATE2-K substrates. Avoid concomitant use; if necessary, monitor closely and adjust the dose of the other drug according to its labeling.
Specific Drugs
Drug |
Interaction |
---|---|
Itraconazole |
No clinically meaningful change in risdiplam exposure with concomitant use of itraconazole (strong CYP3A4 inhibitor) |
Metformin |
Avoid concomitant use with metformin (MATE substrate); if unavoidable, monitor for toxicity and consider dosage reduction of coadministered drug per its labeling |
Midazolam |
No clinically significant change in midazolam (CYP3A4 substrate) exposure |
Risdiplam Pharmacokinetics
Absorption
Shows linear pharmacokinetics after oral doses ranging from 0.6–18 mg in healthy adults and 0.02–0.25 mg/kg in patients with spinal muscular atrophy (SMA).
Bioavailability
Tablets (swallowed whole or dispersed in water) are bioequivalent to the oral solution, regardless of fed or fasted state.
Plasma Concentrations
Steady state reached in 7-14 days.
Median time to maximum plasma concentration: 3.26—4 hours.
Food
Delays peak concentration by ≤1 hour; does not impact overall exposure.
Weight
Weight influences exposure with weight-based dosing achieving consistent exposure across age groups.
Special Populations
No pharmacokinetic changes based on race or gender.
Mild hepatic impairment: slight decrease in risdiplam exposure.
Moderate hepatic impairment: slight increase in risdiplam exposure.
Distribution
Plasma Protein Binding
Primary bound to albumin; 11% unbound.
Elimination
Metabolism
Mainly metabolized by flavin-containing monooxygenase (FMO) 1 and 3; minor contributions from CYP1A1, 2J2, 3A4, and 3A7.
Major inactive metabolite, M1 (inactive).
Elimination Route
53% feces, 14% unchanged.
28% urine, 8% unchanged.
Half-life
50 hours in adults.
Stability
Storage
Oral
Powder for Oral Solution
Store dry powder at 20—25°C in the original container; excursions permitted between 15—30°C.
Store constituted oral solution in original amber bottle to protect from light. Store refrigerated at 2–8°C; do not freeze. Keep upright with cap closed; discard after 64 days.
If refrigeration not available, may store constituted oral solution at room temperature up to 40°C for up to 5 days total; may be removed from and returned to refrigerator, but combined time out of refrigeration should not exceed 5 days.
Tablets
Store at 20—25°C in the original container; excursions permitted between 15—30°C.
Actions
-
Survival of motor neuron 2 (SMN2) splicing modifier.
-
Promotes inclusion of exon 7 to generate full-length SMN2 mRNA and increase production of the SMN protein that is deficient in patients with SMA.
Advice to Patients
-
Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
-
Inform pregnant women and women of reproductive potential that, based on animal studies, risdiplam may cause fetal harm. Before starting treatment, discuss with women of childbearing age whether they are currently pregnant, could be pregnant, or are planning to become pregnant.
-
Advise women of childbearing potential to use effective contraception during treatment with risdiplam and for at least 1 month after stopping risdiplam.
-
Encourage patients to enroll in the risdiplam Pregnancy Registry if they become pregnant while taking risdiplam by calling 1-833-760-1098 or visiting [Web].
-
Advise male patients that their fertility may be compromised while on treatment with risdiplam.
-
If prescribed the oral solution, advise patients to ensure that risdiplam is in liquid form when received from the pharmacy. Instruct patients/caregivers to take risdiplam oral solution after a meal or after breastfeeding at approximately the same time each day. Instruct caregivers to not mix risdiplam oral solution with formula or milk. Instruct patients/caregivers that risdiplam oral solution should be taken immediately after it is drawn up into the reusable oral syringe.
-
If prescribed the oral tablets, advise patients/caregivers to swallow risdiplam tablets whole with water; do not chew, cut, or crush. Alternatively, tablets may be dispersed in 5 mL of room-temperature non-chlorinated water (e.g., filtered) and taken immediately within 10 minutes; do not use other liquids. The dispersion is for oral use only; use risdiplam oral solution for nasogastric or gastrostomy tube administration. Instruct caregivers to wash hands before and after handling. Avoid contact of the dispersed tablet with skin or eyes. If exposure occurs, wash skin with soap and water and rinse eyes with water. Clean spills with a dry paper towel, then wash the area with soap and water. Discard the towel and wash hands thoroughly.
-
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
-
Inform patients of other important precautionary information.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Risdiplam is available through designated specialty pharmacies. Contact manufacturer or consult the risdiplam website ([Web]) for specific availability information.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
For oral solution |
60 mg |
Evrysdi |
Genentech |
Tablets, film-coated |
5 mg |
Evrysdi |
Genentech |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions June 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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