Version May 2024
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: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
Note: Use in patients with renal impairment is based on patient CYP2D6 metabolizer status.
Mild to severe renal impairment (CrCl ≥15 mL/minute):
Extensive metabolizers (EMs): No dosage adjustment necessary.
Intermediate metabolizers (IMs) and poor metabolizers (PMs): Avoid use.
ESRD (CrCl <15 mL/minute with or without dialysis): EMs, IMs, and PMs: Avoid use.
Note: Use in patients with hepatic impairment is based on patient CYP2D6 metabolizer status and concomitant use of CYP2D6 or CYP3A inhibitors.
Mild hepatic impairment (Child-Pugh class A):
Extensive metabolizers (EMs) (without concomitant use of CYP2D6 or CYP3A inhibitors): No dosage adjustment necessary.
EMs taking a weak CYP2D6 inhibitor or a strong, moderate, or weak CYP3A4 inhibitor: 84 mg once daily.
EMs taking a strong or moderate CYP2D6 inhibitor: Use is contraindicated.
Intermediate metabolizers (IMs): Use is contraindicated.
Poor metabolizers (PMs): Use is contraindicated.
Moderate to severe hepatic impairment (Child-Pugh class B and C): EMs, IMs, and PMs: Use is contraindicated.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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%)
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.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 congenital lactase deficiency; concomitant use of a strong CYP3A4 inhibitor in EMs with mild hepatic impairment
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.
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Cerdelga: 84 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
No
Capsules (Cerdelga Oral)
84 mg (per each): $676.18
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Cerdelga: 84 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Oral: Administer with or without food. Swallow capsules whole with water; do not crush, dissolve, or open. Avoid grapefruit or grapefruit juice.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205494Orig1s000lbl.pdf, must be dispensed with this medication.
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).
Substrate of CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak), P-glycoprotein/ABCB1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Adagrasib: May increase the serum concentration of Eliglustat. Risk X: Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Eliglustat. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Eliglustat. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Darunavir: May increase the serum concentration of Eliglustat. Risk X: Avoid combination
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Eliglustat. Risk X: Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Itraconazole: May increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with itraconazole. Use of eliglustat is contraindicated during and for 2 weeks after itraconazole in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider therapy modification
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: 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. Risk D: Consider therapy modification
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: 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). Risk C: Monitor therapy
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
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. Risk C: Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: 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 (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Eliglustat serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Avoid concurrent use.
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.
It is not known if eliglustat is excreted into breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Avoid grapefruit or grapefruit juice.
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)
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.
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
Protein binding: 76% to 83%
Metabolism: Extensive by CYP2D6 (major) and CYP3A4
Bioavailability: EMs: <5%
Half-life elimination: EMs: 6.5 hours; PMs: 8.9 hours
Time to peak: EMs: 1.5 to 2 hours; PMs: 3 hours
Excretion: Urine (41.8%) and feces (51.4%) as inactive metabolites
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
