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SMN2 Splicing Modifier (Spinal Muscular Atrophy — Oral) Pregnancy: Contraindicated — reproductive toxicity in animal studies. Effective contraception mandatory. If pregnancy occurs on risdiplam — refer to teratology information service and specialist.

Risdiplam

Brand names: Evrysdi

Adult dose

Dose: Adults ≥20 kg: 5 mg once daily
Route: Oral solution
Frequency: Once daily after a meal (or after breastfeeding in infants)
Max: 5 mg/day
Spinal muscular atrophy (SMA) types 1, 2, 3 in adults and children from birth. Adults ≥20 kg: 5 mg once daily. Take after meal (not with food — take IMMEDIATELY after eating, not during meal). Oral solution convenience vs nusinersen intrathecal injections. Source: BNF 90; NICE TA700.

Paediatric dose

Dose: 2 months–<2 years: 0.2 mg/kg. 2–<20 kg: 0.25 mg/kg. ≥20 kg: 5 mg once daily mg/kg
Route: Oral solution
Frequency: Once daily after meal or breastfeed
Max: 5 mg/day
Licensed from birth. Weight-based dosing in young children — precision critical. Oral solution 0.75 mg/mL. Risdiplam is the ONLY oral SMA treatment — nusinersen (intrathecal) and onasemnogene abeparvovec (IV gene therapy, one-time) are alternatives. Source: BNF for Children 2024; NICE TA700.

Dose adjustments

Renal

No dose adjustment required.

Hepatic

Severe hepatic impairment: not studied — use with caution. Mild-moderate: no adjustment.

Paediatric weight-based calculator

Licensed from birth. Weight-based dosing in young children — precision critical. Oral solution 0.75 mg/mL. Risdiplam is the ONLY oral SMA treatment — nusinersen (intrathecal) and onasemnogene abeparvovec (IV gene therapy, one-time) are alternatives. Source: BNF for Children 2024; NICE TA700.

Clinical pearls

  • FIREFISH trial (SMA type 1) and SUNFISH trial (SMA types 2/3): risdiplam improved motor function scores significantly vs natural history controls. FIREFISH: 85% of infants achieved sitting without support (vs historical 0%). Landmark — oral liquid taken daily at home vs intrathecal injections in hospital.
  • Oral advantage over nusinersen: nusinersen requires 6 intrathecal injections in first year, then 3 per year lifelong — hospital-based, requiring sedation/anaesthesia in very young infants. Risdiplam is oral solution administered daily at home — transformative for quality of life of patients and families. Particularly important in resource-limited settings or where repeated hospital visits are burdensome.
  • SMN2 splicing mechanism: SMA is caused by SMN1 gene deletion/mutation. All patients retain some SMN2 copies (a near-identical gene that mostly produces a truncated unstable protein). Risdiplam modifies SMN2 pre-mRNA splicing to include exon 7 → full-length functional SMN protein. Higher SMN2 copy number generally predicts better response.
  • Reproductive toxicity — critical counselling: animal studies demonstrate male testicular toxicity and female embryotoxicity. All patients of reproductive potential must use effective contraception during treatment. Males: contraception for ≥4 months after stopping. Females: contraception for ≥4 months after stopping. Sexual partners of male patients also require contraception.
  • NICE TA700: recommended as an option for treating SMA in patients with 1–4 SMN2 copies who have symptomatic SMA. Currently commissioned by NHS England. Discuss with specialist SMA centre (Bristol, London, Sheffield, Newcastle in UK). Source: BNF for Children 2024; Mercuri et al. NEJM 2022 (SUNFISH); NICE TA700; MHRA SPC Evrysdi.

Contraindications

  • Hypersensitivity to risdiplam
  • Reproductive potential: male and female patients must use contraception during treatment and for at least 4 months (women) or 4 months (men) after stopping — reproductive toxicity in animal studies

Side effects

  • Fever, diarrhoea (most common — especially in SMA type 1 young infants)
  • Rash, oral sores (stomatitis — rinse mouth after dose if oral mucositis occurs)
  • Upper respiratory tract infections
  • Reproductive toxicity (men: genotoxicity to sperm; women: animal studies show foetal harm)

Interactions

  • No significant CYP-based drug interactions — risdiplam inhibits MATE1 and MATE2K transporters, which may increase creatinine levels without affecting eGFR. Caution with MATE substrate drugs (metformin — may accumulate; monitor)
  • CYP3A4 inducers (rifampicin): reduce risdiplam levels — avoid or dose increase with specialist guidance

Monitoring

  • Motor function assessments (CHOP-INTEND in young infants; HFMSE in older children — at baseline, 3 months, 6 months, then 6-monthly)
  • Creatinine (risdiplam inhibits MATE transporters — creatinine may rise without true renal impairment; confirm with cystatin C if concerned)
  • Respiratory function (SpO2, sleep study, ventilator use) in SMA type 1/2
  • Reproductive counselling and contraception (all patients of reproductive age)
  • Eye examination (retinal changes observed in animal studies — ophthalmology review annually)

Reference: BNF for Children 2024; Mercuri et al. NEJM 2022 (SUNFISH); NICE TA700; MHRA SPC Evrysdi. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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