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Glucosylceramide synthase inhibitor (substrate reduction therapy)

Eliglustat

Brand names: Cerdelga

Adult dose

Dose: 84mg BD (extensive/intermediate metabolisers); 84mg OD (poor metabolisers) — based on CYP2D6 phenotype
Route: Oral
Frequency: OD–BD

Clinical pearls

  • Type 1 Gaucher disease — alternative to enzyme replacement (imiglucerase, velaglucerase) per UK Lysosomal Storage Disorder Service
  • NICE TA recommendations; specialist metabolic centre
  • CYP2D6 genotyping mandatory before prescribing

Contraindications

  • CYP2D6 ultra-rapid metabolisers (insufficient drug exposure)
  • Concurrent strong CYP2D6 + CYP3A4 inhibitors
  • Severe hepatic impairment
  • Hypersensitivity

Side effects

  • Headache
  • Dizziness
  • Fatigue
  • Nausea
  • Diarrhoea
  • Arthralgia
  • QT prolongation
  • Hepatotoxicity

Interactions

  • CYP2D6 inhibitors (paroxetine, fluoxetine — avoid)
  • CYP3A4 inhibitors
  • QT-prolonging drugs

Monitoring

  • Disease parameters (haematology, splenomegaly, bone)
  • ECG (QT)
  • LFTs
  • CYP2D6 genotype documented

Reference: BNF; NICE TA354; UK LSD National Service; BIMDG; SmPC; https://bnf.nice.org.uk/drugs/eliglustat/. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.