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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 (IMs).
Concomitant use of a moderate or strong CYP2D6 inhibitor with a moderate or strong CYP3A inhibitor in extensive metabolizers (EMs) or intermediate metabolizers (IMs); concomitant use of a strong CYP3A inhibitor in poor metabolizers (PMs) or IMs
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. Note: Dosage has not been studied; however the predicted systemic exposures in these patients are within the range of those observed in clinical studies.
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 strong or moderate CYP2D6 or CYP3A4 inhibitors:
EMs and IMs taking strong or moderate CYP2D6 inhibitors: 84 mg once daily
EMs taking strong or moderate CYP3A inhibitors: 84 mg once daily
Refer to adult dosing.
Mild renal impairment: No dosage adjustment necessary.
Moderate to severe renal impairment: Use is not recommended (has not been studied).
End-stage renal disease (ESRD): Use is not recommended (has not been studied).
Use is not recommended (has not been studied).
Oral: Administer with or without food. Swallow capsules whole with water; do not crush, dissolve, or open. Avoid grapefruit or grapefruit juice.
Avoid grapefruit or grapefruit juice.
Store at 20 ‚ ºC to 25 ‚ ºC (68 ‚ ºF to 77 ‚ ºF); excursions are permitted between 15 ‚ ºC and 30 ‚ ºC (59 ‚ ºF and 86 ‚ ºF).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Cerdelga: 84 mg [contains fd&c blue #2 (indigotine)]
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. 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: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
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
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. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. 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. 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. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. 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 inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Grapefruit Juice: May increase the serum concentration of Eliglustat. Avoid combination
Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
MiFEPRIStone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. 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. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. 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.). Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of Eliglustat. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Vinflunine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Adverse reactions (especially in PMs)
>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%)
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: Use is not recommended 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: Not recommended in hepatic impairment or cirrhosis (has not been studied).
- Renal impairment: Not recommended in patients with moderate to severe renal impairment or end-stage renal disease (ESRD); use with caution in patients with mild renal impairment.
- Poor metabolizers: Dosing has not been studied in poor metabolizers (PMs); however, the predicted systemic exposures in these patients are within the range of those observed in clinical studies; monitor these patients for adverse reactions.
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).
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Adverse events were observed in some animal reproduction studies.
Uncontrolled type 1 Gaucher disease is associated an increased risk of spontaneous abortion; maternal hepatosplenomegaly and thrombocytopenia may also occur and lead to adverse pregnancy outcomes.
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.
Systemic exposure depends upon the patient 's CYP2D6 phenotype; systemic exposure is up to 9-fold higher in poor metabolizers (PMs).
Vd: 835 L
Extensive by CYP2D6 (major) and CYP3A4
Urine (41.8%) and feces (51.4%) as inactive metabolites
EMs: 1.5 to 2 hours; PMs: 3 hours
EMs: 6.5 hours; PMs: 8.9 hours.
76% to 83%
- 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, flatulence, back pain, headache, loss of strength and energy, joint pain, pharyngitis, mouth irritation, or painful extremities. Have patient report immediately to prescriber tachycardia, passing out, arrhythmia, 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.