e-LIG-lu-stat

• Long term treatment of adults with Gaucher disease type 1 who have been tested to be extensive metabolizers (EMs), intermediate metabolizers (IMs) or poor metabolizers (PMs) of the CYP2D6 enzyme system.

• Acts as a specific inhibitor of glucosylceramide synthase, thereby reducing the substrate that accumulates in Gaucher disease type 1.

• Improvement in symptoms of Gaucher’s disease (anemia, thrombocytopenia, bone disease, splenomegaly, and hepatomegaly).

Absorption: EMs — 5% absorbed following oral administration (due to extensive first-pass metabolism).

Distribution: Distributes mainly into plasma.

Metabolism/Excretion: Extensively metabolized, primarily by the CYP2D6 enzyme system, with some metabolism by CYP3A4; 41.8% excreted in urine and 51.4% in feces mostly as metabolites.

Half-life: EMs — 6.5 hr; PMs — 8.9 hr.

Contraindicated in:

• CYP2D6 ultra-rapid metabolizers (may not achieve effective concentrations)
• Concurrent use of strong or moderate CYP2D6 inhibitors with a strong or moderate CYP3A inhibitor in patients who are CYP2D6 EMs or IMs (↑ risk of cardiac arrhythmias)
• History of cardiac disease, long QT syndrome, or concurrent use of Class Ia or Class III antiarrhythmics
• Concurrent ingestion of grapefruit/grapefruit juice
• Moderate or severe renal impairment
• Moderate or severe hepatic impairment in patients who are CYP2D6 EMs (↑ risk of cardiac arrhythmias)
• Mild hepatic impairment in patients who are CYP2D6 EMs who are taking a strong or moderate CYP2D6 inhibitor (↑ risk of cardiac arrhythmias)
• Hepatic impairment (any degree) in patients who are CYP2D6 IMs or PMs (↑ risk of cardiac arrhythmias)
• Use of strong CYP3A inhibitors in patients who are CYP2D6 IMs or PMs (↑ risk of cardiac arrhythmias)
• Lactation: Lactation.

Use Cautiously in:

• CYP2D6 indeterminate metabolizers (dose not known)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Safety and effectiveness not established in children.

CV: ARRHYTHMIAS, palpitations, AV block, QT interval prolongation.

Derm: rash.

GI: diarrhea, flatulence, nausea, oropharyngeal pain, upper abdominal pain, constipation, reflux.

MS: arthralgia, back pain, extremity pain.

Neuro: fatigue, headache, dizziness.

General

Drug-Drug:

• Concurrent use of Class Ia antiarrhythmics (including procainamide and quinidine) or Class III antiarrhythmics (including amiodarone, dofetilide, dronedarone, and sotalol) ↑ risk of cardiac arrhythmias; concurrent use contraindicated.
• Concurrent use of strong CYP3A inducers including carbamazepine, phenobarbital, phenytoin, and rifampin may ↓ blood levels and effectiveness; concurrent use not recommended.
• May ↑ blood levels and effects/risk of toxicity with P-glycoprotein substrates including digoxin (↓ digoxin dose by 30% and monitor digoxin levels), colchicine, dabigatran, and phenytoin (monitor drug levels, consider dose reduction/titration).
• May ↑ blood levels and effects/risk of toxicity with CYP2D6 substrates including metoprolol, tricyclic antidepressants , and phenothiazines; monitor drug levels, consider dose ↓/titration.

Drug-Natural Products:

• St. John's wort↓ blood levels and may ↓ effectiveness; concurrent use not recommended.

Drug-Food:

• Grapefruit/grapefruit juice↑ risk of cardiac arrhythmias; concurrent ingestion contraindicated.

For extensive metabolizers (EMs)

Drug-Drug:

• Concurrent use of strong or moderate CYP2D6 inhibitors and strong or moderate CYP3A inhibitors↑ risk of cardiac arrhythmias; concurrent use contraindicated.
• Concurrent use of strong CYP2D6 inhibitors including paroxetine↑ risk of potentially serious cardiac events; once daily dosing recommended.
• Concurrent use of moderate CYP2D6 inhibitors including terbinafine↑ risk of potentially serious cardiac events; once daily dose recommended.
• Concurrent use of strong CYP3A inhibitors including ketoconazole↑ risk of potentially serious cardiac events; once daily dose recommended.
• Concurrent use of moderate CYP3A inhibitors including fluconazole↑ risk of potentially serious cardiac events; once daily dose recommended.

For intermediate metabolizers (IMs)

Drug-Drug:

• Concurrent use of strong or moderate CYP2D6 inhibitors and strong or moderate CYP3A inhibitors↑ risk of cardiac arrhythmias; concurrent use contraindicated.
• Concurrent use of strong CYP3A inhibitors, including ketoconazole, ↑ risk of cardiac arrhythmias; concurrent use contraindicated.
• Concurrent use of strong CYP2D6 inhibitors including paroxetine↑ risk of potentially serious cardiac events; once daily dose recommended.
• Concurrent use of moderate CYP2D6 inhibitors including terbinafine↑ risk of potentially serious cardiac events; once daily dose recommended.
• Concurrent use of moderate CYP3A inhibitors including fluconazole↑ risk of potentially serious cardiac events; concurrent use not recommended.

For poor metabolizers (PMs)

Drug-Drug:

• Concurrent use of strong CYP3A inhibitors, including ketoconazole, ↑ risk of cardiac arrhythmias; concurrent use contraindicated.
• Concurrent use of moderate CYP3A inhibitors including fluconazole↑ risk of potentially serious cardiac events; concurrent use not recommended.
• Concurrent use of weak CYP3A inhibitors↑ risk of potentially serious cardiac events; concurrent use not recommended.

• PO (Adults): CYP2D6 EMs or IMs — 84 mg twice daily; CYP2D6 PMs — 84 mg once daily; CYP2D6 EMs or IMs taking strong or moderate CYP2D6 inhibitor or CYP2D6 EMs taking strong or moderate CYP3A inhibitor — 84 mg once daily.

• If taking imiglucerase, taliglucerase, or velaglucerase, administer 24 hr after last dose.
• PO: Administer without regard to food, preferably with water. Swallow capsules whole; do not open, crush or chew.

Cerdelga

Therapeutic Classification:

Pharmacologic Classification: glucosylceramide synthase inhibitors

• Capsules: 84 mg;

(blood levels)

• Monitor for an improvement in symptoms including hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone demineralization, and increased appetite and energy level periodically during therapy. Assess liver and spleen size every 6 mo to determine effectiveness of therapy.
• May cause increased ECG intervals (PR, QTc, QRS). Monitor ECG periodically in patients with pre-existing cardiac disease, long QT syndrome, or those taking antiarrhythmics.

• Fatigue (Indications).
• Risk for injury (Indications).

• Instruct patient to take eliglustat as directed. Omit missed doses and take next scheduled dose; do not double doses. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Advise patient to avoid grapefruit and grapefruit juice during therapy.
• Inform patient of the purpose of this medication and the importance of treatment at least every 4 wk. Eliglustst helps control the symptoms but does not cure Gaucher’s disease. Lifelong therapy may be required.
• Advise patient to notify health care professional if palpitations, fainting, or dizziness occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's Wort.
• Rep: Advise female patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.
• Emphasize the importance of follow-up examinations and lab tests.

• Improvement in symptoms of Gaucher’s disease (anemia, thrombocytopenia, bone disease, splenomegaly, and hepatomegaly).

NDC Code^*

• 58468- Genzyme Corporation
  • 58468-0220- Cerdelga
    • 58468-0220-1- 4 BLISTER PACK in 1 CARTON (58468-0220-1) > 14 CAPSULE in 1 BLISTER PACK

• 58468- Genzyme Corporation
  • 58468-0220- Cerdelga
    • 58468-0220-2- 1 BLISTER PACK in 1 CARTON (58468-0220-2) > 14 CAPSULE in 1 BLISTER PACK