Usual Adult Dose for Gaucher Disease

Dose recommendations are provided based on CYP450 2D6 Metabolizer Status:
Extensive metabolizers (EM); Intermediate metabolizers (IM); Poor metabolizers (PM)

EM: 84 mg orally twice a day
IM: 84 mg orally twice a day
PM: 84 mg orally once a day

Dose Reduction: 84 mg orally once a day recommended for:

• EM or IM taking a strong or moderate CYP450 2D6 inhibitors
• EM taking a strong or moderate CYP450 3A inhibitor
• EM with mild hepatic impairment taking a weak CYP450 2D6 inhibitor
• EM with mild hepatic impairment taking a strong, moderate, or weak CYP450 3A inhibitor

Comments:

• CYP450 2D6 ultra-rapid metabolizers (URM) may not achieve adequate drug concentrations to achieve a therapeutic effect.
• Dose recommendations cannot be provided for patients whose genotype cannot be determined (indeterminate metabolizers).

Use: For the long-term treatment of patients with Gaucher disease type 1 who are CYP450 2D6 extensive metabolizers, intermediate metabolizers, or poor metabolizers as detected by an FDA-cleared test.

Renal Dose Adjustments

Doses are based on CYP450 2D6 Metabolizer Status:
Extensive metabolizers (EM):

• Mild to Severe Renal impairment (CrCl greater than 15 mL/min): No dose adjustment recommended
• ESRD (CrCl less than 15 mL/min): Avoid use

Intermediate Metabolizers (IM) and Poor Metabolizers (PM): Avoid use in patients with any degree of renal impairment

Liver Dose Adjustments

Doses are based on CYP450 2D6 Metabolizer Status and Concomitant Use of CYP450 2D6 or CYP450 3A Inhibitors:
Extensive metabolizers (EM):

• Moderate or Severe Hepatic Impairment (Child-Pugh Class B or C): Use is contraindicated
• Mild Hepatic Impairment (Child-Pugh Class A) taking a strong or moderate CYP450 2D6 inhibitor: Use is contraindicated
• Mild Hepatic Impairment (Child-Pugh Class A) taking a weak CYP450 2D6 inhibitor or a strong, moderate, or weak CYP450 3A inhibitor: Reduce dose to 84 mg orally once a day

Intermediate Metabolizers (IM) or Poor Metabolizers (PM): Mild to Severe Hepatic Impairment: Use is contraindicated

Dose Adjustments

• Coadministration with CYP450 2D6 and CYP450 3A inhibitors may increase eliglustat concentrations which may increase risk of cardiac arrhythmias
• Coadministration with strong CYP450 3A inducers may decrease eliglustat concentrations which may reduce efficacy

Recommendations:

• Consult contraindications and drug interactions
• Reduce dose of eliglustat to 84 mg once daily for Extensive Metabolizers (EM) and Intermediate metabolizers (IM) taking strong or moderate CYP450 2D6 inhibitors.
• Reduce dose of eliglustat to 84 mg once daily for EMs taking strong or moderate CYP450 3A inhibitors.

Precautions

CONTRAINDICATIONS:

• Extensive metabolizers (EMs): Concomitant use of strong or moderate CYP450 2D6 inhibitor with a strong or moderate CYP450 3A inhibitor; moderate or severe hepatic impairment; or mild hepatic impairment and taking a strong or moderate CYP450 2D6 inhibitor
• Intermediate metabolizers (IMs): Concomitant use of a strong or moderate CYP450 2D6 inhibitor with a strong or moderate CYP450 3A inhibitor; concomitant use of a strong CYP450 3A inhibitor; or any degree of hepatic impairment
• Poor metabolizers (PMs): Concomitant use of a strong CYP450 3A inhibitor; or any degree of hepatic impairment

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally with or without food, preferably with water
• Swallow capsules whole; do not crush, dissolve, or open capsules
• Avoid consumption of grapefruit or grapefruit juice
• Patients switching from enzyme replacement therapy (ERT) with imiglucerase, velaglucerase alfa, or taliglucerase alfa, may start this drug 24 hours after the last dose of previous ERT

Missed dose: If a dose is missed, take at the next scheduled time; do not double the next dose

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Patients should be instructed to discuss all medications including herbal supplements and vitamins with their healthcare provider; patients should be instructed to avoid grapefruit products.
• Patients who develop palpitations, fainting, and dizziness should inform their health care provider promptly.