Evrysdi Risdiplam powder for oral solution

1. Indications and Usage
Spinal Muscular Atrophy (SMA):
Risdiplam is indicated for the treatment of patients with spinal muscular atrophy (SMA).
Age Restriction:
Safety and effectiveness have not been established in children less than 16 days of age.
2. Dosage and Administration
Preparation:
Risdiplam powder must be constituted by a healthcare professional into an oral solution (0.75 mg/mL) prior to dispensing.
Recommended Dosage:
Initial Treatment (<2 months): 0.15 mg/kg once daily.
Initial Treatment (2 months to <2 years): 0.20 mg/kg once daily.
Initial Treatment (≥2 years, <20 kg): 0.25 mg/kg once daily.
Initial Treatment (≥2 years, ≥20 kg): 5 mg once daily.
Maintenance Dosing: Dosing may be adjusted based on body surface area (BSA) in subsequent visits.
Administration Instructions:
Administer orally once daily at approximately the same time each day.
Can be taken with or without food.
Use only the provided oral syringe. Do not mix with food or other liquids (e.g., milk).
Missed Dose: If a dose is missed, administer within 6 hours of the scheduled time. If >6 hours have passed, skip the dose and take the next one at the regular time.
3. Mechanism of Action
SMN2 Splicing Modifier:
Risdiplam is a small molecule that binds to the RNA of the survival motor neuron 2 (SMN2) gene.
Physiological Effect:
It modifies the splicing of SMN2 pre-mRNA to increase the inclusion of exon 7. This results in an increase in the production of full-length functional survival motor neuron (SMN) protein, which is deficient in SMA patients.
4. Safety and Warnings
Embryo-Fetal Toxicity:
Risdiplam may cause fetal harm. Females of reproductive potential should use effective contraception during treatment and for at least 1 month after the final dose. Males should use contraception for 4 months after the final dose.
Reproductive Toxicity:
Risdiplam may cause impairment of fertility in males.
Hepatotoxicity:
Monitor liver function tests (ALT, AST, and bilirubin) periodically during treatment.
5. Adverse Reactions
Infantile-Onset SMA:
Most common adverse reactions (>10%) include pyrexia (fever), rash, diarrhea, upper respiratory tract infection, pneumonia, constipation, and vomiting.
Late-Onset SMA:
Most common adverse reactions (>10%) include pyrexia, diarrhea, rash, headache, urinary tract infection, and arthralgia.
6. Drug Interactions
MATE Transporter Substrates:
Risdiplam is an inhibitor of MATE transporters (MATE1, MATE2-K). Avoid co-administration with MATE substrate drugs (e.g., metformin).
7. Pharmaceutical Information
Storage:
Powder: Store at room temperature (below 25°C).
Constituted Solution: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Keep the bottle tightly closed and protected from light.
Expiration: Discard the constituted solution after the expiration date on the bottle label.