Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Cerdelga: 84 mg [contains fd&c blue #2 (indigotine)]
Pharmacology
Mechanism of Action
Eliglustat inhibits the enzyme needed to produce glycosphingolipids and decreases the rate of glycosphingolipid glucosylceramide formation. Glucosylceramide accumulates in type 1 Gaucher disease, causing complications specific to this disease.
Pharmacokinetics/Pharmacodynamics
Absorption
Systemic exposure depends upon the patient's CYP2D6 phenotype; systemic exposure is up to 9-fold higher in poor metabolizers (PMs).
Distribution
Vd: Extensive metabolizers (EMs): 835 L
Metabolism
Extensive by CYP2D6 (major) and CYP3A4
Excretion
Urine (41.8%) and feces (51.4%) as inactive metabolites
Time to Peak
EMs: 1.5 to 2 hours; PMs: 3 hours
Half-Life Elimination
EMs: 6.5 hours; PMs: 8.9 hours.
Protein Binding
76% to 83%
Use: Labeled Indications
Gaucher disease: Treatment of adult patients with Gaucher disease type 1 (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs).
Limitations of use: Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of eliglustat to achieve a therapeutic effect. A specific dosage cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).
Contraindications
Use in extensive metabolizers (EMs) with moderate or severe hepatic impairment; use in intermediate metabolizers (IMs) or poor metabolizers (PMs) with any degree of hepatic impairment; concomitant use of a moderate or strong CYP2D6 inhibitor with a moderate or strong CYP3A inhibitor in EMs or IMs; concomitant use of a strong CYP3A inhibitor in PMs or IMs; concomitant use of a moderate or strong CYP2D6 inhibitor in EMs with mild hepatic impairment.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to eliglustat or any component of the formulation; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the Lapp lactase deficiency; concomitant use of a strong CYP3A4 inhibitor in EMs with mild hepatic impairment
Dosage and Administration
Dosing: Adult
Gaucher disease: Oral: Note: Dosage is based on patient CYP2D6 metabolizer status (extensive metabolizers [EMs], intermediate metabolizers [IMs], or poor metabolizers [PMs]) determined by an FDA-cleared test.
EMs and IMs: 84 mg twice daily
PMs: 84 mg once daily.
Missed dose: If a dose is missed, take the prescribed dose at the next scheduled time; do not double the next dose.
Dosage adjustment for concomitant therapy with CYP2D6 or CYP3A4 inhibitors:
EMs taking strong or moderate CYP2D6 inhibitor: 84 mg once daily
EMs taking strong or moderate CYP3A inhibitor: 84 mg once daily
EMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor: Use is contraindicated.
IMs taking strong or moderate CYP2D6 inhibitor: 84 mg once daily
IMs taking strong CYP3A inhibitor: Use is contraindicated.
IMs taking moderate CYP3A inhibitor: Avoid use.
IMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor: Use is contraindicated.
PMs taking strong CYP3A inhibitor: Use is contraindicated.
PMs taking moderate or weak CYP3A inhibitor: Avoid use.
Conversion from imiglucerase, velaglucerase alfa, or taliglucerase alfa: Eliglustat may be administered 24 hours after the last dose of the previous enzyme replacement therapy (ERT).
Dosing: Geriatric
Refer to adult dosing.
Administration
Oral: Administer with or without food. Swallow capsules whole with water; do not crush, dissolve, or open. Avoid grapefruit or grapefruit juice.
Dietary Considerations
Avoid grapefruit or grapefruit juice.
Storage
Store at 20ºC to 25ºC (68ºF to 77ºF); excursions are permitted between 15ºC and 30ºC (59ºF and 86ºF).
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. If used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification
Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy
CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Eliglustat. Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Digoxin: Eliglustat may increase the serum concentration of Digoxin. Management: In patients receiving digoxin, measure digoxin serum concentrations prior to initiating eliglustat. Preemptively reduce digoxin doses by 30% and continue monitoring following eliglustat initiation. Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Grapefruit Juice: May increase the serum concentration of Eliglustat. Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Consider therapy modification
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide. Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
St John's Wort: May decrease the serum concentration of Eliglustat. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs. Monitor therapy
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (if needed) of 50 mg when used with a P-gp inhibitor. Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Adverse Reactions
>10%:
Central nervous system: Headache (13% to 40%), fatigue (14%)
Gastrointestinal: Diarrhea (12%), nausea (10% to 12%)
Neuromuscular & skeletal: Arthralgia (45%), back pain (12%), limb pain (11%)
1% to 10%:
Cardiovascular: Palpitations (5%)
Central nervous system: Migraine (10%), dizziness (8%)
Dermatologic: Skin rash (5%)
Gastrointestinal: Flatulence (10%), upper abdominal pain (10%), dyspepsia (7%), gastroesophageal reflux disease (7%), constipation (5%)
Neuromuscular & skeletal: Weakness (8%)
Respiratory: Oropharyngeal pain (10%), cough (7%)
Warnings/Precautions
Concerns related to adverse effects:
- Arrhythmias: May cause increases in ECG intervals (PR, QTc, and QRS) at substantially elevated eliglustat plasma concentrations.
Disease-related concerns:
- Cardiovascular disease: Avoid use in patients with preexisting cardiac disease (CHF, recent acute MI, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, and in combination with Class IA (eg, quinidine, procainamide) and Class III (eg, amiodarone, sotalol) antiarrhythmic medications (has not been studied).
- Hepatic impairment: Use is contraindicated in extensive metabolizers (EMs) with moderate to severe hepatic impairment and intermediate metabolizers (IMs) or poor metabolizers (PMs) with any degree of hepatic impairment; concomitant use of a moderate or strong CYP2D6 inhibitor in EMs with mild hepatic impairment is also contraindicated.
- Renal impairment: Avoid use in IMs and PMs with any degree of renal impairment and in EMs with ESRD.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Registry: A registry has been established and all patients with Gaucher disease, and health care providers who treat Gaucher disease are encouraged to participate. Information on the International Collaborative Gaucher Group (ICGG) Gaucher Registry may be obtained at https://www.registrynxt.com or by calling 1-800-745-4447 (ext.15500).
Monitoring Parameters
Adverse reactions (especially in PMs); CBC, platelets, prothrombin, electrolytes, chitotriosidase, angiotensin-converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP); MRI or CT scan (liver and spleen volume), skeletal x-rays, DXA; pulmonary function tests; hepatic and renal function, ECG/echocardiography; growth in pediatric patients (Balwani 2016)
Pregnancy
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies.
Uncontrolled type 1 Gaucher disease is associated with an increased risk of spontaneous abortion; maternal hepatosplenomegaly and thrombocytopenia may also occur and lead to adverse pregnancy outcomes.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience abdominal pain, diarrhea, nausea, passing gas, back pain, loss of strength and energy, joint pain, mouth pain, sore throat, cough, constipation, or painful extremities. Have patient report immediately to prescriber severe headache, fast heartbeat, passing out, abnormal heartbeat, or dizziness (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
