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CERDELGA (eliglustat) capsule
These highlights do not include all the information needed to use CERDELGA™ safely and effectively. See full prescribing information for CERDELGA.
CERDELGA™ (eliglustat) capsules, for oral use
Initial U.S. Approval: 2014
INDICATIONS AND USAGE
CERDELGA is a glucosylceramide synthase inhibitor indicated for the long-term treatment of adult patients with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test. (1)
Limitations of Use:
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CYP2D6 ultra-rapid metabolizers may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect (1)
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A specific dosage cannot be recommended for CYP2D6 indeterminate metabolizers (1)
DOSAGE AND ADMINISTRATION
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Select patients using an FDA-cleared test for determining CYP2D6 genotype (2.1)
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CYP2D6 EMs or IMs: 84 mg orally twice daily (2.2)
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CYP2D6 PMs: 84 mg orally once daily (2.2)
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Swallow capsules whole, do not crush, dissolve or open capsules (2.3)
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Avoid eating grapefruit or drinking grapefruit juice (2.3)
DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
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CYP2D6 EMs and IMs taking a strong or moderate CYP2D6 inhibitor with a strong or moderate CYP3A inhibitor (4, 5.1, 7.1, 12.2)
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CYP2D6 IMs and PMs taking a strong CYP3A inhibitor (4, 5.1, 7.1, 12.2)
WARNINGS AND PRECAUTIONS
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ECG Changes and Potential for Cardiac Arrhythmias: Not recommended in patients with pre-existing cardiac disease, long QT syndrome, and concomitant use of Class IA and Class III antiarrhythmics (5.2)
ADVERSE REACTIONS
The most common adverse reactions (≥10%) are: fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-800-745-4447 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
DRUG INTERACTIONS
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Eliglustat is a CYP2D6 and CYP3A substrate. Co-administration of CERDELGA with drugs that inhibit CYP2D6 and CYP3A may significantly increase the exposure to eliglustat and result in prolongation of the PR, QTc, and/or QRS cardiac interval, which could result in cardiac arrhythmias. Consider potential drug interactions prior to and during therapy (5.1, 7.1)
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CYP2D6 IMs and PMs taking moderate CYP3A inhibitors: not recommended (7.1)
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CYP2D6 PMs taking weak CYP3A inhibitors: not recommended (7.1)
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CYP2D6 EMs and IMs taking strong or moderate CYP2D6 inhibitors and CYP2D6 EMs taking strong or moderate CYP3A inhibitors: reduce the dosage to 84 mg once daily (2.2, 7.1)
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Eliglustat is an inhibitor of P-gp and CYP2D6. Co-administration with drugs that are substrates for P-gp or CYP2D6 may result in increased concentrations of the other drug (7.2)
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See Full Prescribing Information for a list of clinically significant drug interactions (7.1, 7.2)
USE IN SPECIFIC POPULATIONS
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Pregnancy: Only administer if the potential benefit justifies the potential risk. Based on animal data, may cause fetal harm (8.1)
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Nursing mothers: Discontinue drug or nursing based on importance of drug to mother (8.3)
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Renal impairment: Not recommended in moderate to severe impairment (8.6)
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Hepatic impairment: Not recommended (8.7)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 8/2014
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
CERDELGA is indicated for the long-term treatment of adult patients with Gaucher disease type 1 (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test [see Dosage and Administration (2.1)].
Limitations of Use:
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Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect [see Clinical Studies (14)].
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A specific dosage cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers) [see Clinical Studies (14)].
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Select patients with Gaucher disease type 1 based on their CYP2D6 metabolizer status. It is recommended patient genotypes be established using an FDA-cleared test for determining CYP2D6 genotype [see Indications and Usage (1)].
2.2 Recommended Adult Dosage
The recommended dosage of CERDELGA is 84 mg twice daily in CYP2D6 EMs and IMs. The recommended dosage in CYP2D6 PMs is 84 mg once daily; appropriate adverse event monitoring is recommended [see Adverse Reactions (6.1)]. The predicted exposures with 84 mg once daily in patients who are CYP2D6 PMs are expected to be similar to exposures observed with 84 mg twice daily in CYP2D6 IMs [see Clinical Pharmacology (12.3)].
Some inhibitors of CYP2D6 and CYP3A are contraindicated with CERDELGA depending on the patient's metabolizer status [see Contraindications (4)]. Co-administration of CERDELGA with other CYP2D6 and CYP3A inhibitors may require dosage adjustment depending on the patient's CYP2D6 metabolizer status to reduce the risk of potentially significant adverse reactions [see Table 3 and Table 4 in Drug Interactions (7.1)].
Reduce the dosage of CERDELGA to 84 mg once daily for:
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CYP2D6 EMs and IMs taking strong or moderate CYP2D6 inhibitors
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CYP2D6 EMs taking strong or moderate CYP3A inhibitors
2.3 Important Administration Instructions
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Swallow capsules whole, preferably with water, and do not crush, dissolve, or open the capsules.
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CERDELGA can be taken with or without food.
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Avoid the consumption of grapefruit or grapefruit juice with CERDELGA because grapefruit is a strong CYP3A inhibitor [see Drug Interactions (7.1)].
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If a dose of CERDELGA is missed, take the prescribed dose at the next scheduled time; do not double the next dose.
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For patients currently treated with imiglucerase, velaglucerase alfa, or taliglucerase alfa, CERDELGA may be administered 24 hours after the last dose of the previous enzyme replacement therapy (ERT).
3 DOSAGE FORMS AND STRENGTHS
CERDELGA is supplied as 84 mg hard gelatin capsules, with a pearl blue-green opaque cap and pearl white opaque body imprinted with "GZ02" in black. Each capsule contains 100 mg eliglustat tartrate, which is equivalent to 84 mg of eliglustat.
4 CONTRAINDICATIONS
CERDELGA is contraindicated in the following patients due to the risk of significantly increased eliglustat plasma concentrations which may result in prolongation of the PR, QTc, and/or QRS cardiac intervals that could result in cardiac arrhythmias. See Table 3 and Table 4 for examples of drugs in each of the categories described [see Drug Interactions (7.1)]:
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EMs or IMs taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor.
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IMs or PMs taking a strong CYP3A inhibitor.
5 WARNINGS AND PRECAUTIONS
5.1 Drug-Drug Interactions
Eliglustat is a CYP2D6 and CYP3A substrate. Drugs that inhibit CYP2D6 and CYP3A metabolism pathways may significantly increase the exposure to eliglustat and result in prolongation of the PR, QTc, and/or QRS cardiac intervals that could result in cardiac arrhythmias [see Clinical Pharmacology (12.2)]. Some drugs that are inhibitors of CYP2D6 and CYP3A are contraindicated with CERDELGA depending on the patient's CYP2D6 metabolizer status [see Contraindications (4)]. See Table 3 and Table 4 for other potentially significant drug interactions [see Drug Interactions (7.1)].
5.2 ECG Changes and Potential for Cardiac Arrhythmias
Use of CERDELGA in patients with pre-existing cardiac conditions has not been studied during clinical trials. Because CERDELGA is predicted to cause increases in ECG intervals (PR, QTc, and QRS) at substantially elevated eliglustat plasma concentrations, use of CERDELGA is not recommended in patients with pre-existing cardiac disease (congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, and in combination with Class IA (e.g., quinidine, procainamide) and Class III (e.g., amiodarone, sotalol) antiarrhythmic medications [see Clinical Pharmacology (12.2)].
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be |
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