Eliglustat

See Full Prescribing Information for a list of clinically significant drug interactions. ( 7.1 , 7.2 )

7.1 Effect of Other Drugs on CERDELGA Coadministration of CERDELGA with: CYP2D6 or CYP3A inhibitors may increase eliglustat concentrations which may increase the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac interval [see Warnings and Precautions (5.1) , Clinical Pharmacology (12.3) ] . strong CYP3A inducers decrease eliglustat concentrations which may reduce CERDELGA efficacy [see Clinical Pharmacology (12.3) ] . See Table 5 for prevention and management of interactions with drugs affecting CERDELGA.

Use of CERDELGA is contraindicated, to be avoided, or may require dosage adjustment depending on the concomitant drug and CYP2D6 metabolizer status [see Dosage and Administration (2.2 , 2.3) , Contraindications (4) , Drug Interactions (7.1) ] . Table 5: Prevention and Management Strategies of Drug Interactions Affecting CERDELGA Based on CYP2D6 Metabolizer Status and Concomitant Interacting Drug Concomitant Drug(s) CYP2D6 Metabolizer Status EMs IMs PMs CYP2D6 Inhibitor Strong Reduce frequency of CERDELGA 84 mg to once daily Continue CERDELGA 84 mg once daily No effect of CYP2D6 inhibitor due to little or no CYP2D6 activity in CYP2D6 PMs.

Moderate Weak Continue CERDELGA 84 mg twice daily CYP3A Inhibitor Strong Reduce frequency of CERDELGA 84 mg to once daily Contraindicated Moderate Avoid coadministration Weak Continue CERDELGA 84 mg twice daily Avoid coadministration CYP2D6 Inhibitor Concomitantly with a strong CYP3A Inhibitor Strong Contraindicated Moderate CYP2D6 Inhibitor Concomitantly with a moderate CYP3A Inhibitor Strong Contraindicated Avoid coadministration Moderate CYP3A Inducer Strong Avoid coadministration

7.2 Effect of CERDELGA on Other Drugs See Table 6 for clinically relevant interactions affecting P-gp or CYP2D6 substrates when coadministered with CERDELGA. Table 6: Prevention and Management Strategies of Drug Interactions Affecting Other Drugs Substrates for P-gp or CYP2D6 Clinical Impact Coadministration of CERDELGA may increase concentrations of drugs that are substrates for P-gp or CYP2D6 [see Clinical Pharmacology (12.3) ] and may increase the risk of toxicity of these drugs. Prevention or Management Digoxin Monitor serum digoxin concentrations before initiating CERDELGA. Reduce digoxin dose by 30% and continue monitoring.

Other P-gp substrates or CYP2D6 substrates Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

8.1 Pregnancy Risk Summary Available data on CERDELGA use in pregnant women includes 20 pregnancies that occurred during the clinical development program and a small number of post-marketing case reports. These data are not sufficient to assess drug-associated risks major birth defects, miscarriage, or adverse maternal or fetal outcomes. 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.

No adverse developmental outcomes were observed with oral administration of eliglustat to pregnant rabbits at dose levels 10 times the recommended human dose [see Data ] . The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women with Gaucher disease type 1 have an increased risk of spontaneous abortion, especially if disease symptoms are not treated and controlled pre-conception 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.

Data Animal data Reproduction studies have been performed in pregnant rats at oral doses up to 120 mg/kg/day (about 6 times the recommended human dose based on body surface area) and in pregnant rabbits at oral doses up to 100 mg/kg/day (about 10 times the recommended human dose based on body surface area) following administration of eliglustat during the period of organogenesis (gestation days 6 to 17 in the rat and 6 to 18 in the rabbit).

In rats, at 120 mg/kg/day (about 6 times the recommended human dose based on body surface area), eliglustat increased the number of late resorptions, dead fetuses and post implantation loss, reduced fetal body weight, and caused fetal cerebral variations (dilated cerebral ventricles), fetal skeletal variations (poor bone ossification) and fetal skeletal malformations (abnormal number of ribs or lumbar vertebra). Eliglustat-related effects…