Generic Name

Risdiplam

Mechanism

Risdiplam binds to the intron 7/exon 7 splice region of the SMN2 transcript.
• Promotes inclusion of exon 7, shifting the splicing balance toward the production of the full‑length, functional SMN protein.
• Acts on the retinal and muscular tissues, achieving systemic distribution without a need for delivery across the blood‑brain barrier.
• Demonstrates a dose‑dependent increase in SMN protein expression in both central and peripheral tissues.

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentration (C_max) reached at ~1–3 h post‑dose.
• Bioavailability: ~60–70 % (unchanged by food).
• Distribution: Widely dispersed; crosses the blood‑brain barrier efficiently.
• Metabolism: Primarily oxidative metabolism and glucuronidation (CYP3A not major).
• Elimination: ~70 % fecal, ~20 % urinary.
• Half‑life: ~18–23 h (supporting twice‑daily dosing).
• Steady‑state: Achieved in ~3–5 days; no significant accumulation with repeated dosing.

Indications

Risdiplam is approved:
• For spinal muscular atrophy (SMA) types 1, 2, and 3 (both pediatric and adult patients).
• Indicated to prevent or reduce the progression of SMA‑related motor neuropathy by increasing SMN protein levels.

Contraindications

• Contraindications: No absolute contraindications; however, caution in patients with severe hepatic impairment.
• Warnings:
• Hypersensitivity: Contact dermatitis, urticaria.
• Pregnancy/Lactation: Category B; avoid if not necessary; fetal safety data limited.
• Hepatic Transaminase Elevations: Monitor ALT/AST; hold dose if >3× upper limit of normal (ULN).
• Use in Children Under 5: Data limited; use with careful monitoring.

Dosing

• Administer with or without food; take at consistent times each day.
• Adjust dose with weight changes (e.g., rapid growth in children).
• Drug interactions: Minimal; avoid potent CYP3A inducers that may affect metabolism.

Adverse Effects

• Common (≥10 %)
• Nausea, vomiting, diarrhea
• Decreased appetite, weight loss
• Headache, fatigue
• Elevated creatine kinase (CK)
• Serious (≤1 %)
• Serious hypersensitivity rash or anaphylaxis
• Hepatotoxicity (↑ALT/AST)
• Peripheral neuropathy (rare)
• Severe GI disturbances (e.g., perforation in susceptible individuals)

Monitoring

• Baseline & periodic: Liver function tests (ALT, AST, ALP, bilirubin).
• CK levels: At baseline, 4–6 weeks, then monthly.
• Weight & growth: Weight check at each visit for pediatric patients.
• Motor function: Use validated scales (HFMSE, CHOP‑INTEND) at baseline and every 3 months.
• Adverse reaction reporting: Immediate reporting of rash, jaundice, or severe GI symptoms.

Clinical Pearls

• Early initiation yields the greatest motor function gains; start as soon as SMA is diagnosed.
• Weight‑based dosing in pediatrics is critical; many patients need dose adjustments as they grow.
• Adherence: Missed doses can markedly reduce SMN protein levels; use pill‑box reminders or caregiver support.
• No need for IV access: Oral formulation reduces hospital visits and caregiver burden.
• Pregnancy & lactation: No established safety data; discuss risk–benefit with the patient.
• Drug interactions: Though minimal, avoid CYP3A inducers (ketoconazole, rifampin) which may lower plasma concentrations.
• Adjuncts: Consider physical therapy and respiratory support concurrently; Risdiplam addresses the underlying neurodegeneration but does not replace supportive care.

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• *This card is intended as a quick reference for clinicians and medical students. For comprehensive prescribing information, always consult the FDA label and individual product monograph.*