eliglustat (Rx)

Brand and Other Names:Cerdelga
  • Print

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule

  • 84mg
more...

Gaucher Disease

Indicated for long-term treatment of adults with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EM), intermediate metabolizers (IM), or poor metabolizers (PM) as detected by an FDA-cleared test for genotype

Dose based on patient's CYP2D6 metabolizer status

CYP2D6 EM or IM: 84 mg PO BID

CYP2D6 PM: 84 mg PO qDay

Dosage Modifications

Coadministration with CYP2D6 inhibitors

  • Strong or moderate (EM or IM): Reduce to 84 mg qDay
  • Weak (EM or IM): Continue 84 mg qDay
  • Strong, moderate, or weak (PM): Continue 84 mg Day

Coadministration with CYP3A4 inhibitors

  • Strong or moderate (EM): Reduce to 84 mg qDay
  • Strong (IM or PM): Contraindicated
  • Moderate (IM or PM): Avoid coadministration
  • Weak (EM or PM): Continue 84 mg BID

Coadministration with CYP2D6 inhibitors plus strong CYP3A inhibitors

  • Strong or moderate (EM, IM, or PM): Contraindicated

Coadministration with CYP2D6 inhibitors plus moderate CYP3A inhibitors

  • Strong or moderate (EM or IM): Contraindicated
  • Strong or moderate (PM): Avoid coadministration

Coadministration with CYP3A inducers

  • Strong (EM, IM, or PM): Avoid coadministration

Hepatic impairment

  • EM, contraindicated
    • Moderate or severe (Child-Pugh B or C)
    • Mild (Child-Pugh A) plus strong or moderate CYP2D6 inhibitor
  • EM, reduce dose frequency
    • Mild (Child-Pugh A) plus weak CYP2D6 inhibitor: Reduce to 84 mg qDay
    • Mild (Child-Pugh A) plus weak, moderate, or strong CYP3A inhibitor: Reduce to 84 mg qDay
  • EM, no dose adjustment
    • Mild (Child-Pugh A): No dose adjustment required unless stated above (ie, taking CYP2D6 or CYP3A inhibitors)
  • IM or PM
    • Any degree of hepatic impairment: Contraindicated

Renal impairment

  • EM
    • Mild, moderate, or severe (CrCl ≥15 mL/min): No dosage adjustment required
    • ESRD (CrCl <15 mL/min), with or without dialysis: Avoid
  • IM or PM
    • Avoid with any degree of renal impairment

Dosing Considerations

Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate serum concentrations to achieve a therapeutic effect

CYP2D6 genotype not determined: Specific dosage cannot be recommended for indeterminate metabolizers

Safety and efficacy not established

Studies did not include sufficient numbers of subjects aged ≥65 yr to determine whether they respond differently from younger subjects

Clinical experience has not identified differences in responses between elderly and younger patients

Next:

Interactions

Interaction Checker

and eliglustat

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Arthralgia (45%)

            Headache (13-40%)

            Fatigue (14%)

            Nausea (10-12%)

            Diarrhea (12%)

            Back pain (12%)

            Extremity pain (11%)

            1-10%

            Upper abdominal pain (10%)

            Migraine (10%)

            Flatulence (10%)

            Oropharyngeal pain (10%)

            Dizziness (8%)

            Asthenia (8%)

            Cough (7%)

            Dyspepsia (7%)

            GERD (7%)

            Constipation (5%)

            Palpitations (5%)

            Rash (5%)

            Previous
            Next:

            Warnings

            Contraindications

            Extensive CYP2D6 metabolizers

            • Coadministration with strong or moderate CYP2D6 inhibitor AND strong or moderate CYP3A inhibitor
            • Moderate or severe hepatic impairment
            • Mild hepatic impairment and taking strong or moderate CYP2D6 inhibitor

            Intermediate CYP2D6 metabolizers

            • Coadministration with strong or moderate CYP2D6 inhibitor AND strong or moderate CYP3A inhibitor
            • Coadministration with strong CYP3A inhibitors
            • Any degree of hepatic impairment

            Poor CYP2D6 metabolizers

            • Coadministration with strong CYP3A inhibitors
            • Any degree of hepatic impairment

            Cautions

            Increases in ECG intervals (PR, QTc, and QRS) occurs at substantially elevated eliglustat plasma concentrations; avoid use in patients with pre-existing cardiac conditions (eg, 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) antiarrhythmics

            Drug interaction overview

            • Eliglustat inhibits P-gp and CYP2D6; coadministration with P-gp or CYP2D6 substrates may result in increased concentrations of the concomitant drug
            • Use of eliglustat is contraindicated, to be avoided, or may require dosage adjustment depending on the concomitant drug and CYP2D6 metabolizer status (ie, EM, IM, PM)
            • CYP2D6 and CYP3A substrate; drugs that inhibit CYP2D6 and CYP3A metabolism may significantly increase eliglustat systemic exposure and result in prolongation of the PR, QTc, and/or QRS cardiac intervals
            • See Dosage Modifications
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Available data on use in pregnant women includes 20 pregnancies that occurred during the clinical development program and a small number of postmarketing case reports

            These data are not sufficient to assess drug-associated risks major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Animal studies

            • In animal reproduction studies in pregnant rats administered oral eliglustat during organogenesis, a spectrum of various developmental abnormalities were observed at doses 6 times the recommended human dose

            Disease-associated risk

            • Women with Gaucher disease type 1 have an increased risk of spontaneous abortion, especially if disease symptoms are not treated and controlled preconception and during a pregnancy
            • Pregnancy may exacerbate existing Gaucher disease type 1 symptoms or result in new disease manifestations
            • Gaucher disease type 1 manifestations may lead to adverse pregnancy outcomes including, hepatosplenomegaly which can interfere with the normal growth of a pregnancy and thrombocytopenia which can lead to increased bleeding and possible hemorrhage

            Lactation

            There are no human data available on the presence of eliglustat in human milk, the effects on the breastfed infant, or the effects on milk production

            Eliglustat and its metabolites were present in the milk of lactating rats

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Gaucher disease is caused by a deficiency of the lysosomal enzyme acid β-glucosidase (ie, glucocerebrosidase), which catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide

            The enzymatic deficiency causes an accumulation of glucosylceramide (GL-1), primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells"

            Eliglustat is a specific inhibitor of glucosylceramide synthase, thereby reducing production of glucosylceramide

            Absorption

            Peak plasma concentration, peak plasma time, and AUC dependent on CYP2D6 phenotype

            CYP2D6 EM

            • Bioavailability: <5% (single dose, significant first-pass metabolism)
            • Peak plasma time: 1.5-2 hr
            • Peak plasma concentration: 12.1-25 ng/mL
            • AUC: 76.3-143 hr•ng/mL

            CYP2D6 IM

            • Peak plasma concentration: 44.6 ng/mL
            • AUC: 306 hr•ng/mL

            CYP2D6 PM

            • Peak plasma time: 3 hr (BID dosing)
            • Peak plasma concentration: 113-137 ng/mL (BID dose); 75 ng/mL (predicted for once-daily dose)
            • AUC: 922-1057 hr•ng/mL (BID dose); 956 hr•ng/mL (predicted for once-daily dose)

            Distribution

            Protein bound: 76-83%

            In the blood, it is mainly distributed in plasma and not RBCs

            Vd: 835 L

            Metabolism

            Extensively metabolized in the liver with high clearance, mainly by CYP2D6 and to a lesser extent CYP3A4

            No active metabolites have been identified

            Elimination

            Half-life: 6.5 hr (EM); 8.9 hr (PM)

            Total body clearance: 88 L/hr

            Excretion: 51.4% feces; 41.8% urine

            Excreted mainly as metabolites

            Pharmacogenomics

            Dosage is based the patient’s CYP2D6 metabolizer status

            Previous
            Next:

            Administration

            Oral Administration

            Swallow capsules whole, do not crush, dissolve, or open capsule

            May take with or without food

            Avoid eating grapefruit or drinking grapefruit juice

            Storage

            Store at 68-77°F (20-25°C) with excursions permitted between 59-86°F (15-30°C)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.