Glucosylceramide synthase inhibitor (substrate reduction therapy) Pregnancy: US label 8.1: available data (20 pregnancies during the clinical development programme plus a small number of post-marketing case reports) are insufficient to assess drug-associated risks of major birth defects, miscarriage or adverse maternal or fetal outcomes. In pregnant rats, a spectrum of developmental abnormalities was observed at doses 6 times the recommended human dose; no adverse developmental outcomes were seen in rabbits at 10 times the recommended human dose.

Eliglustat

Brand names: Cerdelga

Eliglustat is an oral treatment for type 1 Gaucher disease in adults, used as substrate reduction therapy.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 84 mg — CYP2D6 extensive metabolisers (EMs) and intermediate metabolisers (IMs): 84 mg twice daily; CYP2D6 poor metabolisers (PMs): 84 mg once daily

Route: Oral — swallow capsules whole, preferably with water; do not crush, dissolve or open

Frequency: Twice daily (EMs and IMs) or once daily (PMs)

From US prescribing information for Cerdelga (no UK SPC in the fetched bundle) — verify against UK labelling before use. Dosing is based on CYP2D6 metaboliser status; it is recommended that patient genotypes be established using an FDA-cleared CYP2D6 genotype test. Reduce the dosage frequency to 84 mg once daily in CYP2D6 EMs and IMs taking CYP2D6 or CYP3A inhibitors, as set out in the label's Table 2 — EMs without hepatic impairment taking a strong or moderate CYP2D6 inhibitor or a strong or moderate CYP3A inhibitor; EMs with mild (Child-Pugh Class A) hepatic impairment taking a weak CYP2D6 inhibitor or any strong, moderate or weak CYP3A inhibitor; and IMs without hepatic impairment taking a strong or moderate CYP2D6 inhibitor. May be taken with or without food. Avoid grapefruit and grapefruit juice. If a dose is missed, take the prescribed dose at the next scheduled time and do not double the next dose. For patients currently treated with imiglucerase, velaglucerase alfa or taliglucerase alfa, eliglustat may be started 24 hours after the last dose of the previous enzyme replacement therapy. The US label directs the reader to the full prescribing information for dosing in renal or hepatic impairment; those specific recommendations were not present in the fetched sections. Paediatric: safety and effectiveness in paediatric patients have not been established.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Contraindicated by CYP2D6 metaboliser status because of the risk of cardiac arrhythmias from prolongation of the PR, QTc and/or QRS intervals
EMs: taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor
EMs: moderate or severe hepatic impairment; or mild hepatic impairment while taking a strong or moderate CYP2D6 inhibitor
IMs: taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor; taking a strong CYP3A inhibitor; or any degree of hepatic impairment
PMs: taking a strong CYP3A inhibitor; or any degree of hepatic impairment

Side effects

Fatigue
Headache
Nausea
Diarrhoea
Back pain and pain in extremities
Upper abdominal pain

Interactions

CYP2D6 or CYP3A inhibitors — increase eliglustat concentrations and may increase the risk of cardiac arrhythmias from PR, QTc and/or QRS prolongation; use is contraindicated, to be avoided, or requires a reduction in dosing frequency depending on CYP2D6 metaboliser status and inhibitor strength
Strong CYP3A inducers — decrease eliglustat concentrations and may reduce efficacy
Grapefruit or grapefruit juice (strong CYP3A inhibitor) — avoid
Class IA (e.g. quinidine, procainamide) and Class III (e.g. amiodarone, sotalol) antiarrhythmic medicines — avoid use of eliglustat

Clinical monograph

How it works

It inhibits glucosylceramide synthase, reducing the production of glucosylceramide so that less substrate accumulates in cells where the deficient enzyme cannot break it down.

Prescribing in practice

It is metabolised by CYP2D6 and CYP3A, so dosing depends on the patient's CYP2D6 metaboliser status and interacting drugs, and combinations that markedly raise its levels can prolong the QT interval and must be avoided or adjusted.
Suitability and dosing are guided by CYP2D6 genotype, and it is not recommended in CYP2D6 ultra-rapid or indeterminate metabolisers in whom adequate levels cannot be assured.
Treatment should be initiated and supervised by a clinician experienced in the management of Gaucher disease, with review of concomitant medicines for interactions.

Monitoring

Monitor disease response and review for drug interactions and cardiac (QT) risk, taking the patient's CYP2D6 metaboliser status into account.

Counselling the patient

Take it as directed and tell your healthcare team about all other medicines, including over-the-counter products.
Avoid grapefruit juice, which can raise drug levels.
Do not stop or change the dose without specialist advice.

Evidence & guidelines

Its use is supported by randomised controlled trials in type 1 Gaucher disease, including in previously untreated and stabilised patients.

Reference: NICE TA354; UK LSD National Service; BIMDG; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways