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    Eliglustat

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    Mar.28.2024

    Eliglustat

    Indications/Dosage

    Labeled

    • Gaucher disease

    Patient selection:

    • Patients should be selected based on their CYP2D6 metabolizer status, which should be established using an FDA-cleared test for determining CYP2D6 genotype. 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 whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).[57803]

    Off-Label

      † Off-label indication

      For the long-term treatment of patients with Gaucher disease type I (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs)

      NOTE: Eliglustat carries the FDA designation of Orphan Drug for the treatment of Gaucher disease.

      Oral dosage

      Adults who are extensive metabolizers (EMs) of CYP2D6

      84 mg PO twice daily. If coadministered with a strong or moderate CYP2D6 inhibitor or a strong or moderate CYP3A inhibitor, reduce dose to 84 mg PO once daily. Coadministration of a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor is contraindicated.[57803]

      Adults who are intermediate metabolizers (IMs) of CYP2D6

      84 mg PO twice daily. If coadministered with a strong or moderate CYP2D6 inhibitor, reduce dose to 84 mg PO once daily. Coadministration of a strong CYP3A inhibitor or a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor is contraindicated. Coadministration of a moderate CYP3A inhibitor is not recommended.[57803]

      Adults who are poor metabolizers (PMs) of CYP2D6

      84 mg PO once daily. Monitor closely for adverse events. Coadministration of a strong CYP3A inhibitor is contraindicated. Coadministration of a weak or moderate CYP3A inhibitor is not recommended.[57803]

      Therapeutic Drug Monitoring

      Maximum Dosage Limits

      • Adults

        CYP2D6 extensive metabolizers (EMs): 84 mg/dose PO twice daily.

        CYP2D6 intermediate metabolizers (IMs): 84 mg/dose PO twice daily.

        CYP2D6 poor metabolizers (PMs): 84 mg/dose PO once daily.

      • Geriatric

        CYP2D6 extensive metabolizers (EMs): 84 mg/dose PO twice daily.

        CYP2D6 intermediate metabolizers (IMs): 84 mg/dose PO twice daily.

        CYP2D6 poor metabolizers (PMs): 84 mg/dose PO once daily.

      • Adolescents

        Safety and efficacy have not been established.

      • Children

        Safety and efficacy have not been established.

      • Infants

        Safety and efficacy have not been established.

      • Neonates

        Safety and efficacy have not been established.

      Patients with Hepatic Impairment Dosing

      Use eliglustat in patients with hepatic impairment based on CYP2D6 metabolizer status and concomitant use of CYP2D6 or CYP3A inhibitors.[57803]

       

      Extensive metabolizers

      Mild hepatic impairment (Child-Pugh Class A) not taking a CYP2D6 or CYP3A inhibitor: No dosage adjustment necessary.

      Mild hepatic impairment (Child-Pugh Class A) taking a weak CYP2D6 inhibitor or a strong, moderate, or weak CYP3A inhibitor: 84 mg once daily.

      Mild hepatic impairment (Child-Pugh Class A) taking a strong to moderate CYP2D6 inhibitor: Use is contraindicated.

      Moderate or severe hepatic impairment (Child-Pugh Class B or C): Use is contraindicated.

       

      Intermediate and Poor metabolizers

      Use is contraindicated in patients with any degree of hepatic impairment.

      Patients with Renal Impairment Dosing

      Use eliglustat in patients with renal impairment based on the patient's CYP2D6 metabolizer status.[57803]

       

      Extensive metabolizers

      CrCl 15 mL/minute or more: No dosage adjustment needed.

      CrCl less than 15 mL/minute: Do not use in patients with end-stage renal disease (not on dialysis or requiring dialysis).

       

      Intermediate and Poor metabolizers

      Avoid in patients with any degree of renal impairment.

      † Off-label indication
      Revision Date: 03/28/2024, 01:48:00 AM

      References

      57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.

      How Supplied

      Eliglustat Oral capsule

      Cerdelga 84mg Capsule (58468-0220) (Genzyme Corp, a subsidiary of Sanofi) null

      Description/Classification

      Description

      Eliglustat is an oral glucosylceramide synthase inhibitor indicated for the long-term treatment of adult patients with Gaucher disease type 1 (GD1). Unlike enzyme replacement therapies, which break down fatty deposits that build up in cells of patients with Gaucher disease, eliglustat slows the accumulation of the fatty deposits by inhibiting the metabolic process that forms them.[57819] Although ease of oral administration provides substantial benefit over intravenous enzyme replacement therapy, eliglustat use is somewhat limited by cytochrome P450 (CYP450) 2D6 genotype. Eliglustat is primarily metabolized via CYP2D6 and, to a lesser extent, CYP3A. Patient selection should take into account CYP2D6 metabolizer status, as established by a FDA-cleared test. Patients who are CYP2D6 ultra-rapid metabolizers may not achieve therapeutic concentrations of eliglustat. Poor metabolizers require dosage reduction. In addition, depending on the patient's CYP2D6 metabolizer status, concomitant administration of some CYP2D6 and CYP3A inhibitors may be contraindicated or require dosage adjustment to reduce the risk of potentially significant ECG changes.[57803] Eliglustat was approved by the FDA in August 2014.

      Classifications

      • Alimentary Tract and Metabolism
        • Metabolic Disorder Agents
          • Lysosomal Storage Disorder Agents
            • Gauchers Disease Agents
      Revision Date: 03/28/2024, 01:48:00 AM

      References

      57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.57819 - Lukina E, Watman N, Dragosky M. Eliglustat, an investigational oral therapy for Gaucher disease type 1: phase 2 trial results after 4 years of treatment. Blood Cells Mol Dis 2014; doi: 10.1016/j.bcmd.2014.04.002. [Epub ahead of print]

      Administration Information

      General Administration Information

      For storage information, see the specific product information within the How Supplied section.

      Route-Specific Administration

      Oral Administration

      Oral Solid Formulations

      • Capsules should be swallowed whole, preferably with water. Do not crush, dissolve, or open the capsules.
      • May be taken with or without food.
      • Avoid consumption of grapefruit or grapefruit juice.
      • If a dose is missed, instruct the patient to take the prescribed dose at the next scheduled time; do not double the next dose.
      • For patients being treated with imiglucerase, velglucerase alfa, or taliglucerase alfa, eliglustat may be administered 24 hours after the last dose of the previous enzyme replacement therapy.[57803]

      Clinical Pharmaceutics Information

      From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
        Revision Date: 03/28/2024, 01:48:00 AM

        References

        57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.

        Adverse Reactions

        Mild

        • abdominal pain
        • arthralgia
        • asthenia
        • back pain
        • cough
        • diarrhea
        • dizziness
        • dyspepsia
        • fatigue
        • flatulence
        • gastroesophageal reflux
        • headache
        • nausea
        • rash

        Moderate

        • constipation
        • migraine
        • palpitations
        • QT prolongation

        Severe

        • arrhythmia exacerbation

        Headache (13—40%) and fatigue (14%) were among the most common adverse reactions reported in eliglustat-treated patients (n = 126) during clinical trials. Headache (40%) and migraine (10%) were common in treatment-naive patients (n = 20), while headache (13%), fatigue (14%), dizziness (8%), and asthenia (8%) were frequently reported in patients switching from enzyme replacement therapy (n = 106).[57803]

        Back pain (12%) and extremity pain (11%) were among the most common adverse reactions reported in eliglustat-treated patients (n = 126) during clinical trials; both were reported more frequently that placebo in patients switching from enzyme replacement therapy (n = 106). Arthralgia (45%) was also reported in treatment-naive patients (n = 20).[57803]

        Nausea (10—12%), diarrhea (12%), and upper abdominal pain (10%) were among the most commonly reported adverse events occurring in eliglustat-treated patients (n = 126) during clinical trials. Nausea, flatulence, and oropharyngeal pain occurred in 10% of treatment-naive patients (n = 20). Similar rates of nausea (12%) were reported in patients switching from enzyme replacement therapy (n = 106); in this population, diarrhea (12%), upper abdominal pain (10%), dyspepsia (7%), gastroesophageal reflux (7%), and constipation (5%) were also reported.[57803]

        Cough and rash (unspecified) were reported in 7% an 5% of patients, respectively, being treated with eliglustat (n = 106) during an open-label imiglucerase-controlled trial of patients switching from enzyme replacement therapy.[57803]

        Palpitations were reported in 5% of patients being treated with eliglustat (n = 106) during an open-label imiglucerase-controlled trial of patients switching from enzyme replacement therapy. Eliglustat is predicted to cause QT prolongation and other increases in ECG intervals (e.g., PR, QRS) and, potentially, cardiac arrhythmias (arrhythmia exacerbation) at substantially elevated plasma concentrations. Although clinically relevant interval prolongation did not occur during a double-blind, single-dose, placebo- and positive-controlled crossover study in 42 healthy subjects (highest mean eliglustat concentration: 237 ng/ml), concentration-related increases for the placebo-corrected change from baseline in PR, QRS, and QT intervals were observed. Based on pharmacokinetic and pharmacodynamic modeling, eliglustat concentrations of 500 ng/ml are predicted to cause mean increase in the PR, QRS, and QTcF intervals of 22, 7, and 13 msec, respectively. Hence, eliglustat is not recommended for use in patients with pre-existing cardiac disease, long QT syndrome, or in combination with a Class IA or Class III antiarrhythmic. Eliglustat is contraindicated in patients at risk for significantly increased eliglustat plasma concentrations; these patients include extensive or intermediate CYP2D6 metabolizers taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor and intermediate or poor CYP2D6 metabolizers taking a strong CYP3A inhibitor. In addition, eliglustat use is not recommended in poor or intermediate CYP2D6 metabolizers taking a moderate CYP3A inhibitor or poor CYP2D6 metabolizers taking a weak CYP3A inhibitor.[57803]

        Revision Date: 03/28/2024, 01:48:00 AM

        References

        57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.

        Contraindications/Precautions

        Absolute contraindications are italicized.

        • apheresis
        • AV block
        • bradycardia
        • breast-feeding
        • cardiomyopathy
        • celiac disease
        • females
        • fever
        • geriatric
        • heart failure
        • hepatic disease
        • human immunodeficiency virus (HIV) infection
        • hyperparathyroidism
        • hypocalcemia
        • hypokalemia
        • hypomagnesemia
        • hypothermia
        • hypothyroidism
        • long QT syndrome
        • myocardial infarction
        • pheochromocytoma
        • pregnancy
        • QT prolongation
        • renal failure
        • renal impairment
        • rheumatoid arthritis
        • sickle cell disease
        • sleep deprivation
        • stroke
        • systemic lupus erythematosus (SLE)

        Due to the risk of QT prolongation, the use of eliglustat in patients with pre-existing cardiac disease (e.g., congestive heart failure, recent acute myocardial infarction), bradycardia, cardiac arrhythmias, or congenital or acquired long QT syndrome is not recommended. Use eliglustat with caution in patients with conditions that may increase the risk of QT prolongation including AV block, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. In addition, because eliglustat is a CYP2D6 and CYP3A substrate, drugs that inhibit these metabolic pathways may significantly increase the exposure to eliglustat, resulting in prolongation of cardiac intervals and cardiac arrhythmia. For this reason, depending on the patient's CYP2D6 metabolizer status, some CYP2D6 and CYP3A inhibitors are contraindicated with eliglustat; coadministration of other CYP2D6 and CYP3A inhibitors may require eliglustat dosage adjustment.[28432] [28457] [56592] [65180] [57803]

        Eliglustat clearance is reduced in patients with hepatic disease. Dosage adjustments are required in patients who are extensive metabolizers with mild hepatic impairment (Child-Pugh A) taking a weak CYP2D6 inhibitor or a strong, moderate, or weak CYP3A inhibitor. Eliglustat is contraindicated in patients who are extensive metabolizers with moderate or severe hepatic impairment (Child-Pugh B or C) or mild hepatic impairment (Child-Pugh A) taking a strong or moderate CYP2D6 inhibitor. Additionally, eliglustat is contraindicated in patients who are intermediate or poor metabolizers with any degree of hepatic impairment. Decreased metabolism may lead to increased exposure and a higher risk of QT prolongation and cardiac arrhythmia.[57803]

        Use eliglustat in patients with renal impairment and renal failure based on the patient's CYP2D6 metabolizer status. In patients who are extensive metabolizers, no dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment (estimated creatinine clearance at least 15 mL/minute). Avoid eliglustat use in extensive metabolizers with end-stage renal disease (estimated creatinine clearance less than 15 mL/minute) and in intermediate and poor metabolizers with any degree of renal impairment.[57803]

        Adequate and well-controlled studies have not been conducted in pregnant women. In animal reproduction studies, a spectrum of anomalies at eliglustat doses 6 times the recommended human dose were observed in orally dosed rats; these anomalies included an increased number of late resorptions, dead fetuses and post implantation loss, reduced fetal body weight, fetal cerebral variations (dilated cerebral ventricles), fetal skeletal variations (poor bone ossification), and fetal skeletal malformations (abnormal number of ribs or lumbar vertebra). However, no fetal harm was observed with oral administration to pregnant rabbits at doses 10 times the recommended human dose. In development studies, eliglustat did not show any significant adverse effects on pre- and postnatal development in rats at doses 5 times the recommended human dose. Eliglustat should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[57803]

        According to the manufacturer, a decision should be made whether to discontinue breast-feeding or discontinue eliglustat. It is not known whether eliglustat is present in human milk.[57803] For women who wish to breast-feed, potential alternative treatments might include enzyme replacement therapies. Enzymes such as alglucerase, imiglucerase, taliglucerase alfa, and velaglucerase alfa are likely to be degraded by the infant's digestive sytem and unlikely to reach the systemic circulation of a nursing infant. Limited data in a report from a panel of clinicians that treat Gaucher's disease indicated that breast-feeding complications were reduced in women treated with alglucerase or imiglucerase postpartum. No adverse effects on the nursing infants were reported secondary to enzyme replacement therapy. Consider reducing the duration of breast-feeding to avoid excessive bone loss in the mother.[49246] Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

        Revision Date: 03/28/2024, 01:48:00 AM

        References

        28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.49246 - Zimran A, Morris E, Mengel E et al. The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause). Blood Cells Mol Dis 2009;43:264-88.56592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/

        Mechanism of Action

        Eliglustat is a specific inhibitor of glucosylceramide (GL-1) synthase that acts as a substrate reduction therapy for Gaucher disease type 1 (GD1). Gaucher disease is a lysosomal storage disorder characterized by a deficiency in the enzyme acid beta-glucosidase (glucocerebrosidase). Acid beta-glucosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. Enzymatic deficiency results in accumulation of the beta-glucosidase substrate, GL-1, primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells". As an inhibitor of GL-1 synthase, eliglustat reduces the synthesis of the substrate GL-1 to balance production with the impaired rate of degradation.[57803][57818] [57819]

         

        Clinical features of GD1 are reflective of accumulation of Gaucher cells in the liver, spleen, bone marrow, and other organs. Presence of Gaucher cells in the bone marrow and spleen lead to clinically significant anemia and thrombocytopenia. Accumulation of Gaucher cells in the liver, spleen, and bone marrow results in organomegaly and skeletal disease. Clinically, the use of eliglustat has reduced spleen and liver size and improved anemia and thrombocytopenia.[57803][57818]

        Revision Date: 03/28/2024, 01:48:00 AM

        References

        57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.57818 - Shayman JA. Eliglustat tartrate: glucosylceramide synthase inhibitor treatment of Type 1 Gaucher Disease. Drugs Future 2010;35:613-620.57819 - Lukina E, Watman N, Dragosky M. Eliglustat, an investigational oral therapy for Gaucher disease type 1: phase 2 trial results after 4 years of treatment. Blood Cells Mol Dis 2014; doi: 10.1016/j.bcmd.2014.04.002. [Epub ahead of print]

        Pharmacokinetics

        Eliglustat is administered orally. It is moderately bound to plasma proteins (76% to 83%) and, in the blood, is mainly distributed in the plasma (not red blood cells). The large Vd (835 L) after intravenous administration to CYPD26 extensive metabolizers (EMs) suggests wide tissue distribution. Eliglustat is extensively metabolized in the liver primarily by CYP2D6 and to a lesser extent CYP3A4. Primary metabolic pathways involve sequential oxidation of the octanoyl moiety followed by oxidation of the 2,3-dihydro-1,4-benzodioxane moiety (or a combination of the 2 pathways) resulting in multiple inactive oxidative metabolites. No active metabolites have been identified. The majority of the administered dose is excreted as metabolites in the urine (42%) and feces (51%). In healthy CYP2D6 EMs, clearance is approximately 88 L/hour. Terminal half-life is approximately 6.5 hours in CYP2D6 EMs and 8.9 hours in poor metabolizers (PMs).[57803]

         

        Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4, and P-gp

        Eliglustat is metabolized primarily by CYP2D6 and to a lesser extent CYP3A4; eliglustat is also a P-glycoprotein (P-gp) substrate. Drugs that inhibit CYP2D6 and CYP3A pathways may significantly increase eliglustat exposure; elevated eliglustat concentrations can result in PR, QRS, and/or QT prolongation and cardiac arrhythmias. CYP2D6 metabolizer status plays a critical role in determining eliglustat's pharmacokinetics. In extensive or intermediate CYP2D6 metabolizers, taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor is a contraindication for eliglustat use. In intermediate or poor CYP2D6 metabolizers, taking a strong CYP3A inhibitor is a contraindication for eliglustat use; concomitant use of a moderate CYP3A inhibitor and eliglustat is not recommended. In poor CYP2D6 metabolizers, concomitant use of a weak CYP3A inhibitor and eliglustat is not recommended. Eliglustat is also an inhibitor of CYP2D6 and the efflux transporter P-gp. Hence, co-administration of eliglustat with drugs that are substrates for CYP2D6 or P-gp may result in increased concentrations of the concomitant drug.[57803]

        Route-Specific Pharmacokinetics

        Oral Route

        Oral bioavailability of eliglustat is low (less than 5% in EMs) due to significant first-pass metabolism. Systemic exposure (Cmax and AUC) depends on CYP2D6 phenotype. Food does not have a clinically significant effect on eliglustat pharmacokinetics. During pharmacokinetic analysis, administration with a high fat meal decreased Cmax by 15% with no change in AUC.[57803]

         

        CYP2D6 extensive metabolizers (EMs)

        In CYP2D6 EMs, eliglustat pharmacokinetics are time-dependent and systemic exposure increases in a more than dose proportional manner. After multiple doses of 84 mg PO twice daily, AUC increases approximately 2-fold from time after the first dose to steady state. After multiple doses (84 mg PO twice daily), a mean Cmax of 12 to 25 ng/mL occurs 1.5 to 2 hours after administration. Mean AUC ranges from 76 to 143 hours x ng/mL.[57803]

         

        CYP2D6 intermediate metabolizers (IMs)

        In CYP2D6 IMs, eliglustat pharmacokinetics are time-dependent and systemic exposure increases in a more than dose proportional manner. In a single IM subject, the Cmax and AUC after multiple doses (84 mg PO twice daily) were 45 ng/mL and 306 hours x ng/mL, respectively.[57803]

         

        CYP2D6 poor metabolizers (PMs)

        In CYP2D6 PMs, eliglustat pharmacokinetics are expected to be linear and time-independent. Compared to EMs, systemic exposure after similar doses at steady state is 7- to 9-fold higher in PMs. After multiple doses (84 mg PO twice daily) a mean Cmax of 113 to 137 ng/mL occurs 3 hours after administration. Mean AUC ranges from 922 to 1,057 hours x ng/mL. Oral dosing of eliglustat 84 mg PO once daily has not been studied in PMs; however, using a physiologically-based pharmacokinetic model, the predicted Cmax and AUC are 75 ng/mL and 956 hours x ng/mL, respectively, after this dose.[57803]

        Special Populations

        Hepatic Impairment

        In patients who were extensive metabolizers (EMs) with mild hepatic impairment (n = 6) and moderate hepatic impairment (n = 7), the Cmax was increased by 1.2- fold and 2.8- fold, respectively, compared to EMs with normal hepatic function. The AUC was also increased in patients who were EMs with mild hepatic impairment (1.2- fold increase) and moderate hepatic impairment (5.2- fold increase). The effect of hepatic impairment is highly variable with the coefficients of variation (CVs%) of 135% and 110% for Cmax and 171% and 121% for AUC in CYP2D6 EMs with mild and moderate hepatic impairment, respectively. Eliglustat has not been studied in patients who are CYP2D6 intermediate and poor metabolizers with mild and moderate hepatic impairment. The effect of severe hepatic impairment in patients with any CYP2D6 phenotype is unknown.[57803]

        Renal Impairment

        Eliglustat pharmacokinetics were similar in CYP2D6 extensive metabolizers (EMs) with severe renal impairment and healthy CYP2D6 EMs. Eliglustat has not been studied in patients who are EMs with end-stage renal disease (ESRD) or in intermediate or poor metabolizers with any degree of renal impairment.[57803]

        Geriatric

        Age (18 to 71 years) does not appear to affect eliglustat pharmacokinetics.[57803]

        Gender Differences

        Gender does not appear to affect eliglustat pharmacokinetics.[57803]

        Ethnic Differences

        Race (most were Caucasian, including those of Ashkenazi Jewish descent; however, the following populations were included: African American, American Indians, Hispanics, and Asians) does not appear to affect eliglustat pharmacokinetics.[57803]

        Revision Date: 03/28/2024, 01:48:00 AM

        References

        57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.

        Pregnancy/Breast-feeding

        pregnancy

        Adequate and well-controlled studies have not been conducted in pregnant women. In animal reproduction studies, a spectrum of anomalies at eliglustat doses 6 times the recommended human dose were observed in orally dosed rats; these anomalies included an increased number of late resorptions, dead fetuses and post implantation loss, reduced fetal body weight, fetal cerebral variations (dilated cerebral ventricles), fetal skeletal variations (poor bone ossification), and fetal skeletal malformations (abnormal number of ribs or lumbar vertebra). However, no fetal harm was observed with oral administration to pregnant rabbits at doses 10 times the recommended human dose. In development studies, eliglustat did not show any significant adverse effects on pre- and postnatal development in rats at doses 5 times the recommended human dose. Eliglustat should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[57803]

        breast-feeding

        According to the manufacturer, a decision should be made whether to discontinue breast-feeding or discontinue eliglustat. It is not known whether eliglustat is present in human milk.[57803] For women who wish to breast-feed, potential alternative treatments might include enzyme replacement therapies. Enzymes such as alglucerase, imiglucerase, taliglucerase alfa, and velaglucerase alfa are likely to be degraded by the infant's digestive sytem and unlikely to reach the systemic circulation of a nursing infant. Limited data in a report from a panel of clinicians that treat Gaucher's disease indicated that breast-feeding complications were reduced in women treated with alglucerase or imiglucerase postpartum. No adverse effects on the nursing infants were reported secondary to enzyme replacement therapy. Consider reducing the duration of breast-feeding to avoid excessive bone loss in the mother.[49246] Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

        Revision Date: 03/28/2024, 01:48:00 AM

        References

        49246 - Zimran A, Morris E, Mengel E et al. The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause). Blood Cells Mol Dis 2009;43:264-88.57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.

        Interactions

        Level 1 (Severe)

        • Adagrasib
        • Aprepitant, Fosaprepitant
        • Berotralstat
        • Cisapride
        • Delavirdine
        • Dextromethorphan; Quinidine
        • Dronedarone
        • Fedratinib
        • Fluconazole
        • grapefruit juice
        • Itraconazole
        • Ketoconazole
        • Levoketoconazole
        • Pimozide
        • Posaconazole
        • Quinidine
        • Quinine
        • Saquinavir
        • Thioridazine
        • Tipranavir

        Level 2 (Major)

        • Abiraterone
        • Acetaminophen; Aspirin; Diphenhydramine
        • Acetaminophen; Chlorpheniramine
        • Acetaminophen; Chlorpheniramine; Dextromethorphan
        • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
        • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
        • Acetaminophen; Chlorpheniramine; Phenylephrine
        • Acetaminophen; Diphenhydramine
        • Amiodarone
        • Amisulpride
        • Amlodipine
        • Amlodipine; Atorvastatin
        • Amlodipine; Benazepril
        • Amlodipine; Celecoxib
        • Amlodipine; Olmesartan
        • Amlodipine; Valsartan
        • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
        • Amoxicillin; Clarithromycin; Omeprazole
        • Anagrelide
        • Arsenic Trioxide
        • Artemether; Lumefantrine
        • Asciminib
        • Asenapine
        • Atazanavir
        • Atazanavir; Cobicistat
        • Avacopan
        • Azithromycin
        • Bedaquiline
        • Belumosudil
        • Betrixaban
        • Bicalutamide
        • Bictegravir; Emtricitabine; Tenofovir Alafenamide
        • Buprenorphine
        • Buprenorphine; Naloxone
        • Bupropion
        • Bupropion; Naltrexone
        • Capivasertib
        • Carbamazepine
        • Ceritinib
        • Chloramphenicol
        • Chloroquine
        • Chlorpheniramine
        • Chlorpheniramine; Codeine
        • Chlorpheniramine; Dextromethorphan
        • Chlorpheniramine; Dextromethorphan; Phenylephrine
        • Chlorpheniramine; Dextromethorphan; Pseudoephedrine
        • Chlorpheniramine; Hydrocodone
        • Chlorpheniramine; Ibuprofen; Pseudoephedrine
        • Chlorpheniramine; Phenylephrine
        • Chlorpheniramine; Pseudoephedrine
        • Chlorpromazine
        • Cimetidine
        • Cinacalcet
        • Ciprofloxacin
        • Citalopram
        • Clarithromycin
        • Clozapine
        • Cobicistat
        • Cocaine
        • Codeine; Phenylephrine; Promethazine
        • Codeine; Promethazine
        • Colchicine
        • Conivaptan
        • Crizotinib
        • Cyclosporine
        • Dabigatran
        • Dacomitinib
        • Dalfopristin; Quinupristin
        • Danazol
        • Daridorexant
        • Darifenacin
        • Darunavir
        • Darunavir; Cobicistat
        • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
        • Desflurane
        • Dextromethorphan; Bupropion
        • Dextromethorphan; Diphenhydramine; Phenylephrine
        • Digoxin
        • Diltiazem
        • Diphenhydramine
        • Diphenhydramine; Ibuprofen
        • Diphenhydramine; Naproxen
        • Diphenhydramine; Phenylephrine
        • Disopyramide
        • Docetaxel
        • Dofetilide
        • Doxorubicin
        • Doxorubicin Liposomal
        • Droperidol
        • Duloxetine
        • Duvelisib
        • Elbasvir; Grazoprevir
        • Elexacaftor; tezacaftor; ivacaftor
        • Eluxadoline
        • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
        • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
        • Emtricitabine; Rilpivirine; Tenofovir alafenamide
        • Emtricitabine; Tenofovir alafenamide
        • Encorafenib
        • Entrectinib
        • Enzalutamide
        • Eribulin
        • Erythromycin
        • Everolimus
        • Fexinidazole
        • Fingolimod
        • Flecainide
        • Fluoxetine
        • Fluvoxamine
        • Fosamprenavir
        • Foscarnet
        • Fosphenytoin
        • Fostamatinib
        • Gemtuzumab Ozogamicin
        • Givosiran
        • Glasdegib
        • Halogenated Anesthetics
        • Haloperidol
        • Histrelin
        • Hydroxychloroquine
        • Ibutilide
        • Idelalisib
        • Iloperidone
        • Imatinib
        • Indinavir
        • Inotuzumab Ozogamicin
        • Isavuconazonium
        • Isoflurane
        • Isoniazid, INH
        • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
        • Isoniazid, INH; Rifampin
        • Istradefylline
        • Ivacaftor
        • Ivosidenib
        • Lansoprazole; Amoxicillin; Clarithromycin
        • Lapatinib
        • Larotrectinib
        • Lefamulin
        • Lenacapavir
        • Lenvatinib
        • Letermovir
        • Leuprolide
        • Leuprolide; Norethindrone
        • Levamlodipine
        • Lithium
        • Lofexidine
        • Lonafarnib
        • Lopinavir; Ritonavir
        • Lumacaftor; Ivacaftor
        • Lumacaftor; Ivacaftor
        • Macimorelin
        • Maprotiline
        • Maribavir
        • Mefloquine
        • Methadone
        • Methamphetamine
        • Mexiletine
        • Midostaurin
        • Mifepristone
        • Mirabegron
        • Mirtazapine
        • Mitotane
        • Mobocertinib
        • Moxifloxacin
        • Naldemedine
        • Nanoparticle Albumin-Bound Sirolimus
        • Nefazodone
        • Nelfinavir
        • Nicardipine
        • Nilotinib
        • Niraparib; Abiraterone
        • Nirmatrelvir; Ritonavir
        • Nirogacestat
        • Olanzapine
        • Olanzapine; Fluoxetine
        • Olanzapine; Samidorphan
        • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
        • Ondansetron
        • Osilodrostat
        • Osimertinib
        • Oxaliplatin
        • Ozanimod
        • Pacritinib
        • Palbociclib
        • Paliperidone
        • Panobinostat
        • Paroxetine
        • Pazopanib
        • Pentamidine
        • Perindopril; Amlodipine
        • Phenobarbital
        • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
        • Phenytoin
        • Pimavanserin
        • Pirtobrutinib
        • Pitolisant
        • Ponesimod
        • Pralsetinib
        • Primidone
        • Probenecid; Colchicine
        • Procainamide
        • Promethazine
        • Promethazine; Dextromethorphan
        • Promethazine; Phenylephrine
        • Propafenone
        • Quetiapine
        • Quizartinib
        • Ranitidine
        • Ranolazine
        • Relugolix
        • Relugolix; Estradiol; Norethindrone acetate
        • Repotrectinib
        • Ribociclib
        • Ribociclib; Letrozole
        • Rifampin
        • Rifapentine
        • Rimegepant
        • Ritlecitinib
        • Ritonavir
        • Rolapitant
        • Rucaparib
        • Selpercatinib
        • Sevoflurane
        • Siponimod
        • Solifenacin
        • Sorafenib
        • Sotalol
        • Spironolactone
        • Spironolactone; Hydrochlorothiazide, HCTZ
        • St. John's Wort, Hypericum perforatum
        • Streptogramins
        • Tamoxifen
        • Telmisartan; Amlodipine
        • Tenofovir Alafenamide
        • Tenofovir Alafenamide
        • Terbinafine
        • Tetrabenazine
        • Tezacaftor; Ivacaftor
        • Ticagrelor
        • Tolterodine
        • Topotecan
        • Toremifene
        • Trandolapril; Verapamil
        • Trazodone
        • Triptorelin
        • Trofinetide
        • Tucatinib
        • Ubrogepant
        • Valproic Acid, Divalproex Sodium
        • Vandetanib
        • Vemurafenib
        • Venetoclax
        • Venlafaxine
        • Verapamil
        • Viloxazine
        • Vincristine
        • Vincristine Liposomal
        • Vonoprazan
        • Vonoprazan; Amoxicillin
        • Vonoprazan; Amoxicillin; Clarithromycin
        • Voriconazole
        • Vorinostat
        • Voxelotor
        • Zafirlukast
        • Ziprasidone

        Level 3 (Moderate)

        • Acetaminophen; Caffeine; Dihydrocodeine
        • Acetaminophen; Codeine
        • Acetaminophen; Dextromethorphan
        • Acetaminophen; Dextromethorphan; Doxylamine
        • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
        • Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine
        • Acetaminophen; Dextromethorphan; Phenylephrine
        • Acetaminophen; Dextromethorphan; Pseudoephedrine
        • Acetaminophen; Hydrocodone
        • Afatinib
        • Albuterol; Budesonide
        • Alfuzosin
        • Amitriptyline
        • Apixaban
        • Apomorphine
        • Aripiprazole
        • Aspirin, ASA; Carisoprodol; Codeine
        • Atomoxetine
        • Atorvastatin
        • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
        • Bismuth Subsalicylate; Metronidazole; Tetracycline
        • Brimonidine; Timolol
        • Brompheniramine; Dextromethorphan; Phenylephrine
        • Brompheniramine; Pseudoephedrine; Dextromethorphan
        • Budesonide
        • Budesonide; Formoterol
        • Budesonide; Glycopyrrolate; Formoterol
        • Butalbital; Acetaminophen; Caffeine; Codeine
        • Butalbital; Aspirin; Caffeine; Codeine
        • Cabotegravir; Rilpivirine
        • Carvedilol
        • Celecoxib
        • Celecoxib; Tramadol
        • Chlordiazepoxide; Amitriptyline
        • Clobazam
        • Clofazimine
        • Clomipramine
        • Codeine
        • Codeine; Guaifenesin
        • Codeine; Guaifenesin; Pseudoephedrine
        • Dasatinib
        • Degarelix
        • Desipramine
        • Desvenlafaxine
        • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
        • Dextromethorphan
        • Dextromethorphan; Guaifenesin
        • Dextromethorphan; Guaifenesin; Phenylephrine
        • Dextromethorphan; Guaifenesin; Pseudoephedrine
        • Dolasetron
        • Dolutegravir; Rilpivirine
        • Donepezil
        • Donepezil; Memantine
        • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
        • Dorzolamide; Timolol
        • Doxepin
        • Dutasteride; Tamsulosin
        • Edoxaban
        • Efavirenz
        • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
        • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
        • Eletriptan
        • Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate
        • Emtricitabine; Tenofovir Disoproxil Fumarate
        • Enasidenib
        • Escitalopram
        • Fostemsavir
        • Gefitinib
        • Gemifloxacin
        • Gilteritinib
        • Glecaprevir; Pibrentasvir
        • Glyburide
        • Glyburide; Metformin
        • Goserelin
        • Homatropine; Hydrocodone
        • Hydrocodone
        • Hydrocodone; Ibuprofen
        • Hydroxyzine
        • Imipramine
        • Lamivudine; Tenofovir Disoproxil Fumarate
        • Levofloxacin
        • Loperamide
        • Loperamide; Simethicone
        • Lorcaserin
        • Maraviroc
        • Metoprolol
        • Metoprolol; Hydrochlorothiazide, HCTZ
        • Metronidazole
        • Nebivolol
        • Nebivolol; Valsartan
        • Nortriptyline
        • Ofloxacin
        • Oliceridine
        • Pasireotide
        • Peginterferon Alfa-2b
        • Perphenazine; Amitriptyline
        • Primaquine
        • Propranolol
        • Protriptyline
        • Rifaximin
        • Rilpivirine
        • Risperidone
        • Rivaroxaban
        • Romidepsin
        • Sertraline
        • Sirolimus
        • Sodium Stibogluconate
        • Sofosbuvir; Velpatasvir
        • Sofosbuvir; Velpatasvir; Voxilaprevir
        • Stiripentol
        • Sunitinib
        • Tacrolimus
        • Talazoparib
        • Tamsulosin
        • Telavancin
        • Temsirolimus
        • Tenofovir Disoproxil Fumarate
        • Thiothixene
        • Timolol
        • Tramadol
        • Tramadol; Acetaminophen
        • Triclabendazole
        • Tricyclic antidepressants
        • Trimipramine
        • Vardenafil
        • Voclosporin

        Level 4 (Minor)

        • Cobimetinib
        • Deutetrabenazine
        • Dexmedetomidine
        • Etrasimod
        • Fluphenazine
        • Granisetron
        • Morphine
        • Morphine; Naltrexone
        • Perphenazine
        • Prochlorperazine
        • Trifluoperazine
        Abiraterone: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of abiraterone and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both abiraterone and a strong or moderate CYP3A inhibitor is contraindicated. Abiraterone is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration with CYP2D6 inhibitors, such as abiraterone, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Physiology-based pharmacokinetic (PBPK) models suggest that another moderate CYP2D6 inhibitor may increase the Cmax and AUC of eliglustat 3.8- and 4.5-fold, respectively, in EMs and 1.6-fold (both Cmax and AUC) in IMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a moderate 2D6 inhibitor and a moderate 3A4 inhibitor may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs. [44156] [57803] Acetaminophen; Aspirin; Diphenhydramine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled diphenhydramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however coadministration of eliglustat with both diphenhydramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of diphenhydramine warrants modification of eliglustat therapy. Diphenhydramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as diphenhydramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single diphenhydramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., diphenhydramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34522] [34523] [57803] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with eliglustat may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Eliglustat is a moderate inhibitor of CYP2D6. [30282] [57803] Acetaminophen; Chlorpheniramine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] Acetaminophen; Chlorpheniramine; Dextromethorphan: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Acetaminophen; Dextromethorphan: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Acetaminophen; Diphenhydramine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled diphenhydramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however coadministration of eliglustat with both diphenhydramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of diphenhydramine warrants modification of eliglustat therapy. Diphenhydramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as diphenhydramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single diphenhydramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., diphenhydramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34522] [34523] [57803] Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with eliglustat may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of eliglustat could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If eliglustat is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Eliglustat is a moderate inhibitor of CYP2D6. [30379] [39926] [56303] [57803] Adagrasib: (Contraindicated) Coadministration of adagrasib and eliglustat is contraindicated. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). Concomitant use also results in additive risk for QT/QTc interval prolongation and torsade de pointes. Eliglustat is a CYP3A and CYP2D6 substrate and adagrasib is a strong CYP3A and moderate CYP2D6 inhibitor. Both medications have been associated with QT interval prolongation. [57803] [68325] Afatinib: (Moderate) If the concomitant use of eliglustat and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of eliglustat. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and eliglustat is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib. [55331] [57803] Albuterol; Budesonide: (Moderate) Coadministration of oral budesonide and eliglustat may result in increased plasma concentrations of budesonide. Monitor patients closely for corticosteroid-related adverse effects; if appropriate, consider reducing the budesonide dosage and titrating to clinical effect. Budesonide is a substrate of the intestinal drug efflux pump, P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor. [34354] [57803] Alfuzosin: (Moderate) Use caution when administering alfuzosin with eliglustat due to the potential for QT prolongation. Alfuzosin may prlong the QT interval in a dose-dependent manner. Additionally, eliglustat is predicted to cause PR, QRS, and/or QT prlongation at significantly elevated plasma concentrations. [28261] [57803] Amiodarone: (Major) Coadministration of amiodarone and eliglustat is not recommended. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Amiodarone is an inhibitor of CYP2D6 and a weak inhibitor of CYP3A and is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Amiodarone-mediated inhibition of CYP2D6 and CYP3A in a patient receiving eliglustat may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [28224] [28432] [28457] [56579] [57803] Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with eliglustat. Amisulpride causes dose- and concentration- dependent QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [65068] Amitriptyline: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Amlodipine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Amlodipine; Atorvastatin: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] (Moderate) Coadministration of atorvastatin and eliglustat may result in increased plasma concentrations of atorvastatin. Monitor patients closely for atorvastatin-related adverse effects including myalgia, myopathy, myasthenia, and/or rhabdomyolysis; if appropriate, consider reducing the atorvastatin dosage and titrating to clinical effect. Atorvastatin is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [34486] [41275] [41277] [57803] Amlodipine; Benazepril: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Amlodipine; Celecoxib: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of celecoxib and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Celecoxib is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as celecoxib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28317] [57803] Amlodipine; Olmesartan: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Amlodipine; Valsartan: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Amoxicillin; Clarithromycin; Omeprazole: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of clarithromycin and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both clarithromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and clarithromycin can independently prolong the QT interval, and coadministration increases this risk. Clarithromycin is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors such as clarithromycin increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [25238] [28225] [57803] Anagrelide: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include anagrelide. [30163] [57803] Apixaban: (Moderate) Coadministration of apixaban and eliglustat may increase exposure to apixaban and increase the risk of bleeding; monitor patients closely. Apixaban is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [52739] [57803] Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with eliglustat since concurrent use may increase the risk of QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. [28661] [57803] Aprepitant, Fosaprepitant: (Contraindicated) Use of aprepitant, fosaprepitant with eliglustat is either not recommended or requires dosage adjustment depending on the patient's CYP2D6 metabolizer status and the dosage and/or frequency of aprepitant (or fosaprepitant); alternative agents may be preferred in patients receiving eliglustat. Aprepitant is a weak-to-moderate dose-dependent inhibitor of CYP3A. When administered as a 3-day oral regimen (125 mg/80 mg/80 mg), aprepitant is a moderate CYP3A4 inhibitor and inducer; as a single 125 mg or 40 mg dose of oral aprepitant, or as a 150 mg IV dose of fosaprepitant, the CYP3A4 inhibition is weak. CYP3A4 inhibition continues for at least 4 days after oral administration of a multi-day aprepitant regimen, and for 2 days after a single dose of fosaprepitant given intravenously. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 intermediate and poor metabolizers (IMs and PMs) because a larger portion of the eliglustat dose is metabolized via CYP3A. The coadministration of eliglustat with both a multi-day oral aprepitant regimen and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. In PMs, use of either aprepitant or fosaprepitant together at any dosage with eliglustat (with or without a CYP2D6 inhibitor) is not recommended. In IMs, a single dose of aprepitant 40 mg or fosaprepitant 150 mg (weak CYP3A inhibition) may be given without eliglustat dosage adjustment; however, multi-day regimens of oral aprepitant (moderate CYP3A inhibition) are not recommended. In extensive metabolizers (EMs), a single dose of aprepitant 40 mg or fosaprepitant 150 mg may be given without eliglustat dosage adjustment; however, multi-day aprepitant regimens require interim eliglustat dosage adjustment to 84 mg PO once daily. Repeated dosing at any aprepitant dose may have increased CYP3A inhibitory effects, and hence, an increased risk for clinically significant adverse events. [30676] [40027] [57803] Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of eliglustat. Patients receiving both a CYP3A inhibitor plus eliglustat may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may increase aripiprazole exposure and risk for side effects and may increase the risk of QT/QTc prolongation and TdP in some patients. Aripiprazole is a CYP2D6 and CYP3A substrate; eliglustat is a moderate CYP2D6 inhibitor; both medications have been associated with QT interval prolongation. [42845] [53394] [57803] [60196] Arsenic Trioxide: (Major) Avoid coadministration of eliglustat and arsenic trioxide. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should be expected with the administration of arsenic trioxide. [28226] [57803] [59438] Artemether; Lumefantrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of artemether; lumefantrine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both artemether; lumefantrine and a strong or moderate CYP3A inhibitor is contraindicated. Artemether; lumefantrine is a strong CYP2D6 inhibitor associated with QT prolongation. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of eliglustat and artemether; lumefantrine may result in additive effects on the QT interval, and potentially, increased plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [35401] [57803] Asciminib: (Major) Coadministration of eliglustat and asciminib is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Asciminib is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67087] Asenapine: (Major) Avoid coadministration of asenapine and eliglustat. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Asenapine increases the QT interval and should be not administered with other drugs that increase the QT interval. [36343] [57803] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Atazanavir: (Major) Coadministration of atazanavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). Use of these agents together is also contraindicated in any patient also receiving a moderate or strong CYP2D6 inhibitor, such as ritonavir. In extensive CYP2D6 metabolizers (EMs), coadministration of eliglustat and atazanavir requires dosage adjustment of eliglustat to 84 mg PO once daily. Atazanavir is a strong CYP3A inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Use of these drugs together may result in increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is greatest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [28142] [57803] Atazanavir; Cobicistat: (Major) Coadministration of atazanavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). Use of these agents together is also contraindicated in any patient also receiving a moderate or strong CYP2D6 inhibitor, such as ritonavir. In extensive CYP2D6 metabolizers (EMs), coadministration of eliglustat and atazanavir requires dosage adjustment of eliglustat to 84 mg PO once daily. Atazanavir is a strong CYP3A inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Use of these drugs together may result in increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is greatest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [28142] [57803] (Major) Coadministration of eliglustat and cobicistat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with cobicistat and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as cobicistat, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. The product labeling for cobicistat states that coadministration of other drugs for which altered plasma concentrations are associated with serious and/or life-threatening effects is contraindicated; however, the interaction between ketoconazole (another potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. [28142] [32432] [34557] [57803] [57923] [58000] Atomoxetine: (Moderate) Concomitant use of atomoxetine and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28405] [57803] [59321] Atorvastatin: (Moderate) Coadministration of atorvastatin and eliglustat may result in increased plasma concentrations of atorvastatin. Monitor patients closely for atorvastatin-related adverse effects including myalgia, myopathy, myasthenia, and/or rhabdomyolysis; if appropriate, consider reducing the atorvastatin dosage and titrating to clinical effect. Atorvastatin is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [34486] [41275] [41277] [57803] Avacopan: (Major) Coadministration of eliglustat and avacopan is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Avacopan is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67036] Azithromycin: (Major) Avoid coadministration of azithromycin with eliglustat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28855] [43974] [57803] [65157] [65170] Bedaquiline: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include bedaquiline. [52746] [57803] Belumosudil: (Major) Coadministration of eliglustat and belumosudil is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Belumosudil is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [66808] Berotralstat: (Contraindicated) Coadministration of berotralstat and eliglustat is contraindicated in extensive or intermediate CYP2D6 metabolizers (EMs or IMs). Avoid coadministration in poor CYP2D6 metabolizers (PMs). In PMs also receiving a strong CYP3A inhibitor, coadministration is contraindicated. Eliglustat is a CYP3A and CYP2D6 substrate; berotralstat is a moderate inhibitor of CYP3A and moderate inhibitor of CYP2D6. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [57803] [66159] Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving eliglustat. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving eliglustat. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; eliglustat inhibits P-gp. [57803] [62037] Bicalutamide: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of bicalutamide and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of bicalutamide and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Bicalutamide is a weak CYP3A4 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP3A4 inhibitors, such as bicalutamide, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [31102] [57803] Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [57803] [57923] [60269] [60614] [60688] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [36894] [57803] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [36894] [57803] Brimonidine; Timolol: (Moderate) Coadministration of timolol and eliglustat may result in increased plasma concentrations of timolol. Consider reducing the dosage of oral timolol and titrating to clinical effect. Timolol is a CYP2D6 substrate; eliglustat is a CYP2D6 inhibitor. [28540] [57803] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Budesonide: (Moderate) Coadministration of oral budesonide and eliglustat may result in increased plasma concentrations of budesonide. Monitor patients closely for corticosteroid-related adverse effects; if appropriate, consider reducing the budesonide dosage and titrating to clinical effect. Budesonide is a substrate of the intestinal drug efflux pump, P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor. [34354] [57803] Budesonide; Formoterol: (Moderate) Coadministration of oral budesonide and eliglustat may result in increased plasma concentrations of budesonide. Monitor patients closely for corticosteroid-related adverse effects; if appropriate, consider reducing the budesonide dosage and titrating to clinical effect. Budesonide is a substrate of the intestinal drug efflux pump, P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor. [34354] [57803] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Coadministration of oral budesonide and eliglustat may result in increased plasma concentrations of budesonide. Monitor patients closely for corticosteroid-related adverse effects; if appropriate, consider reducing the budesonide dosage and titrating to clinical effect. Budesonide is a substrate of the intestinal drug efflux pump, P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor. [34354] [57803] Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with eliglustat. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If these drugs are used together, consider the potential for additive effects on the QT interval. [41235] [57803] [59321] [60270] Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with eliglustat. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If these drugs are used together, consider the potential for additive effects on the QT interval. [41235] [57803] [59321] [60270] Bupropion: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving bupropion. Eliglustat is contraindicated in EMs and IMs who are receiving bupropion plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving bupropion plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving bupropion plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. A strong CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 8.4-fold and 2.3-fold in extensive and intermediate metabolizers, respectively. Strong CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs). [41086] [57803] Bupropion; Naltrexone: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving bupropion. Eliglustat is contraindicated in EMs and IMs who are receiving bupropion plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving bupropion plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving bupropion plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. A strong CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 8.4-fold and 2.3-fold in extensive and intermediate metabolizers, respectively. Strong CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs). [41086] [57803] Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with eliglustat as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [44376] [57803] Capivasertib: (Major) Avoid concomitant use of eliglustat and capivasertib due to the risk for increased eliglustat exposure which may increase the risk for eliglustat-related adverse effects. If coadministration is necessary, management recommendations vary based on the patient's CYP2D6 metabolizer status, concomitant medications, and hepatic function. In patients who are extensive CYP2D6 metabolizers (EMs): reduce the dose of eliglustat to 84 mg once daily; concomitant use is contraindicated in patients with mild hepatic impairment (Child-Pugh Class A) and in those who are also receiving a moderate or strong CYP3A inhibitor. In patients who are intermediate CYP2D6 metabolizers (IMs): reduce the dose of eliglustat to 84 mg once daily; concomitant use is contraindicated if the patient is also receiving a moderate or strong CYP3A inhibitor. In patients who are CYP2D6 poor metabolizers (PMs): avoid concomitant use. Eliglustat is a CYP2D6 and CYP3A substrate and capivasertib is a moderate CYP2D6 and weak CYP3A inhibitor. A moderate CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 4.5-fold and 1.6-fold in EMs and IMs, respectively. [57803] [69896] Carbamazepine: (Major) Coadministration of eliglustat and carbamazepine significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. Carbamazepine is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. [57803] Carvedilol: (Moderate) Coadministration of carvedilol and eliglustat may result in increased plasma concentrations of carvedilol. Monitor patients closely for carvedilol-related adverse effects including dizziness and vasodilation, and consider reducing the carvedilol dosage and titrating to clinical effect. Carvedilol is a CYP2D6 and P-gp substrate; eliglustat is a CYP2D6 and P-gp inhibitor. [28537] [34487] [57803] Celecoxib: (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of celecoxib and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Celecoxib is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as celecoxib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28317] [57803] Celecoxib; Tramadol: (Moderate) Coadministration of tramadol and eliglustat may result in a reduction in the metabolic conversion and clearance of tramadol, increasing the risk for serious adverse events including seizures and serotonin syndrome. In addition, coadministration of tramadol and eliglustat may result in decreased analgesia. If coadministration is necessary, monitor patients closely for tramadol-related adverse effects and diminished analgesic efficacy. The analgesic activity of tramadol is due to both the parent drug and the pharmacologically active metabolite M1. Because the metabolism of tramadol to M1 is dependent on CYP2D6 and eliglustat is an inhibitor of CYP2D6, therapeutic response may be affected. [28314] [57803] (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of celecoxib and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Celecoxib is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as celecoxib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28317] [57803] Ceritinib: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of ceritinib and eliglustat is contraindicated. The coadministration of eliglustat with both ceritinib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. In other patients, avoid coadministration of ceritinib and eliglustat if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Additionally, reduce the dose of eliglustat to 84 mg PO once daily in extensive CYP2D6 metabolizers (EMs). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of eliglustat with CYP3A inhibitors such as ceritinib increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [57094] [57803] Chloramphenicol: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of chloramphenicol and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both chloramphenicol and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Chloramphenicol is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as chloramphenicol, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [29624] [57803] Chlordiazepoxide; Amitriptyline: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Chloroquine: (Major) Avoid coadministration of chloroquine with eliglustat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28229] [28230] [28231] [29758] [57803] [65157] [65170] Chlorpheniramine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] Chlorpheniramine; Codeine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Chlorpheniramine; Dextromethorphan: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Chlorpheniramine; Hydrocodone: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] (Moderate) Concomitant use of hydrocodone with eliglustat may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of eliglustat could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If eliglustat is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Eliglustat is a moderate inhibitor of CYP2D6. [30379] [39926] [56303] [57803] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] Chlorpheniramine; Phenylephrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] Chlorpheniramine; Pseudoephedrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled chlorpheniramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however, coadministration of eliglustat with both chlorpheniramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of chlorpheniramine warrants modification of eliglustat therapy. Chlorpheniramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is also a substrate and inhibitor of CYP2D6 as well as a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as chlorpheniramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single chlorpheniramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., chlorpheniramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34390] [57803] [57935] Chlorpromazine: (Major) Coadministration of chlorpromazine and eliglustat may result in increased concentrations of the phenothiazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of chlorpromazine and titrating to clinical effect. Chlorpromazine is a CYP2D6 substrate associated with an established risk of QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28415] [43065] [57803] Cimetidine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of cimetidine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Cimetidine is a weak CYP3A (and CYP2D6) inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 and CYP3A inihibitors, such as cimetidine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [34364] [50762] [57803] Cinacalcet: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving cinacalcet. Eliglustat is contraindicated in EMs and IMs who are receiving cinacalcet plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving cinacalcet plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving cinacalcet plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor. A moderate CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 4.5-fold and 1.6-fold in extensive and intermediate metabolizers, respectively. Moderate CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs). [52414] [57803] Ciprofloxacin: (Major) Coadministration of eliglustat and ciprofloxacin is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with ciprofloxacin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with moderate CYP3A inhibitors, such as ciprofloxacin, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Both eliglustat and ciprofloxacin can independently prolong the QT interval, and coadministration increases this risk. [43411] [56579] [57803] Cisapride: (Contraindicated) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Because of the potential for torsades de pointes (TdP), use of cisapride with eliglustat is contraindicated. [47221] [57803] Citalopram: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include citalopram. [28269] [57803] Clarithromycin: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of clarithromycin and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both clarithromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and clarithromycin can independently prolong the QT interval, and coadministration increases this risk. Clarithromycin is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors such as clarithromycin increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [25238] [28225] [57803] Clobazam: (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of clobazam and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Clobazam is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as clobazam, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [46370] [57803] Clofazimine: (Moderate) Concomitant use of clofazimine and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [57803] [63936] Clomipramine: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Clozapine: (Major) Coadministration of clozapine and eliglustat may result in increased plasma concentrations of clozapine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of clozapine and titrating to clinical effect. In addition, if eliglustat is discontinued while the patient is taking clozapine, monitor for a lack of antipsychotic efficacy, and increase the clozapine dose as clinically necessary. Clozapine is a CYP2D6 substrate associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28262] [57803] Cobicistat: (Major) Coadministration of eliglustat and cobicistat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with cobicistat and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as cobicistat, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. The product labeling for cobicistat states that coadministration of other drugs for which altered plasma concentrations are associated with serious and/or life-threatening effects is contraindicated; however, the interaction between ketoconazole (another potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. [28142] [32432] [34557] [57803] [57923] [58000] Cobimetinib: (Minor) If concurrent use of cobimetinib and eliglustat is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and eliglustat is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions. [57803] [60281] Cocaine: (Major) Coadministration of cocaine and eliglustat may result in increased plasma concentrations of eliglustat and an increased risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Cocaine is a strong inhibitor of CYP2D6 and a weak inhibitor of CYP3A4; eliglustat is a CYP2D6 and CYP3A substrate. FDA-approved labeling states the coadministration of a strong CYP2D6 inhibitor, such as cocaine, and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily in extensive or intermediate CYP2D6 metabolizers (EMs or IMs). In poor metabolizers (PMs), coadministration of weak a CYP3A inhibitor, such as cocaine, and eliglustat is not recommended. In addition, coadministration of eliglustat with both a strong or moderate CYP2D6 inhibitor (e.g., cocaine) and a strong or moderate CYP3A inhibitor is contraindicated in all patients. Although this interaction may be more likely to occur with the illicit systemic use of cocaine, cocaine is well absorbed topically from mucous membranes and, thus, may also pose risk when used as a topical anesthetic. [27100] [57076] [57803] Codeine: (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Codeine; Phenylephrine; Promethazine: (Major) Coadministration of promethazine and eliglustat may result in increased concentrations of the phenothiazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of promethazine and titrating to clinical effect. Promethazine is a CYP2D6 substrate associated with a possible risk of QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28225] [55578] [57803] (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Codeine; Promethazine: (Major) Coadministration of promethazine and eliglustat may result in increased concentrations of the phenothiazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of promethazine and titrating to clinical effect. Promethazine is a CYP2D6 substrate associated with a possible risk of QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28225] [55578] [57803] (Moderate) Concomitant use of codeine with eliglustat may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of eliglustat could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If eliglustat is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat is a moderate inhibitor of CYP2D6. [33654] [34883] [57803] Colchicine: (Major) Avoid concomitant use of colchicine and eliglustat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and eliglustat is a P-gp inhibitor. [36114] [57803] [58111] [63965] [69117] Conivaptan: (Major) Avoid coadministration of eliglustat with conivaptan in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate. Conivaptan is a moderate inhibitor of CYP3A. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [31764] [57803] Crizotinib: (Major) Avoid coadministration of crizotinib with eliglustat in all patients due to the risk of QT prolongation. If concomitant use is unavoidable in extensive CYP2D6 metabolizers (EMs), reduce the dose of eliglustat to 84 mg PO once daily; monitor ECGs for QT prolongation and monitor electrolytes. In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of crizotinib and eliglustat is not recommended. The coadministration of eliglustat with both crizotinib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and crizotinib can independently prolong the QT interval, and coadministration increases this risk. Crizotinib is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as crizotinib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [45458] [57803] Cyclosporine: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of cyclosporine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of cyclosporine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Monitor therapeutic cyclosporine concentrations closely and adjust the dosage as necessary. The coadministration of eliglustat with both cyclosporine and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Cyclosporine is a moderate CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and a P-gp inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as cyclosporine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. In addition, coadministration of eliglustat with P-gp substrates (e.g., cyclosporine) may result in increased concentrations of the concomitant drug. Although specific recommendations are not available, when eliglustat is given in combination with digoxin, another narrow therapeutic index P-gp substrate, an empiric digoxin dosage reduction of 30% followed by careful monitoring is recommended. [28404] [57803] Dabigatran: (Major) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with eliglustat, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like eliglustat in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with eliglustat, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. [42121] [57803] Dacomitinib: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of dacomitinib and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both dacomitinib and a strong or moderate CYP3A inhibitor is contraindicated. Dacomitinib is a strong inhibitor of CYP2D6; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as dacomitinib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [63584] Dalfopristin; Quinupristin: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of dalfopristin; quinupristin and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Dalfopristin; quinupristin is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [28491] [57803] Danazol: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of danazol and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of the agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both danazol and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Danazol is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [34717] [57803] Daridorexant: (Major) Coadministration of eliglustat and daridorexant is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; daridorexant is a weak CYP3A inhibitor. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67248] Darifenacin: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of darifenacin and eliglustat is not recommended. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both darifenacin and a moderate or strong CYP3A inhibitor is contraindicated in all patients. Darifenacin is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as darifenacin, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [30711] [57803] Darunavir: (Major) Coadministration of darunavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). Use of these agents together is also contraindicated in any patient also receiving a moderate or strong CYP2D6 inhibitor, such as ritonavir. In extensive CYP2D6 metabolizers (EMs), coadministration of eliglustat and darunavir requires dosage adjustment of eliglustat to 84 mg PO once daily. Darunavir is a strong CYP3A inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Use of these drugs together may result in increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is greatest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [32432] [34557] [47165] [57803] Darunavir; Cobicistat: (Major) Coadministration of darunavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). Use of these agents together is also contraindicated in any patient also receiving a moderate or strong CYP2D6 inhibitor, such as ritonavir. In extensive CYP2D6 metabolizers (EMs), coadministration of eliglustat and darunavir requires dosage adjustment of eliglustat to 84 mg PO once daily. Darunavir is a strong CYP3A inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Use of these drugs together may result in increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is greatest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [32432] [34557] [47165] [57803] (Major) Coadministration of eliglustat and cobicistat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with cobicistat and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as cobicistat, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. The product labeling for cobicistat states that coadministration of other drugs for which altered plasma concentrations are associated with serious and/or life-threatening effects is contraindicated; however, the interaction between ketoconazole (another potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. [28142] [32432] [34557] [57803] [57923] [58000] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of darunavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). Use of these agents together is also contraindicated in any patient also receiving a moderate or strong CYP2D6 inhibitor, such as ritonavir. In extensive CYP2D6 metabolizers (EMs), coadministration of eliglustat and darunavir requires dosage adjustment of eliglustat to 84 mg PO once daily. Darunavir is a strong CYP3A inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Use of these drugs together may result in increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is greatest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [32432] [34557] [47165] [57803] (Major) Coadministration of eliglustat and cobicistat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with cobicistat and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as cobicistat, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. The product labeling for cobicistat states that coadministration of other drugs for which altered plasma concentrations are associated with serious and/or life-threatening effects is contraindicated; however, the interaction between ketoconazole (another potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. [28142] [32432] [34557] [57803] [57923] [58000] (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [57803] [57923] [60269] [60614] [60688] Dasatinib: (Moderate) Use dasatinib with caution in combination with eliglustat as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [32387] [57803] Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving eliglustat as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [46869] [57803] Delavirdine: (Contraindicated) Coadministration of delavirdine and eliglustat is contraindicated. Delavirdine is a strong CYP3A inhibitor and in vitro studies have shown that it also reduces CYP2D6 activity; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A and CYP2D6 inhibitors is expected to increase plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28476] [57803] Desflurane: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include halogenated anesthetics. [57803] Desipramine: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Desvenlafaxine: (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of desvenlafaxine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Desvenlafaxine is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as desvenlafaxine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [34940] [57803] Deutetrabenazine: (Minor) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and eliglustat. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [61845] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Dexmedetomidine: (Minor) QT/QTc prolongation can occur with concomitant use of dexmedetomidine and eliglustat although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP. [57803] [67509] Dextromethorphan: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Dextromethorphan; Bupropion: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving bupropion. Eliglustat is contraindicated in EMs and IMs who are receiving bupropion plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving bupropion plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving bupropion plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. A strong CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 8.4-fold and 2.3-fold in extensive and intermediate metabolizers, respectively. Strong CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs). [41086] [57803] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled diphenhydramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however coadministration of eliglustat with both diphenhydramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of diphenhydramine warrants modification of eliglustat therapy. Diphenhydramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as diphenhydramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single diphenhydramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., diphenhydramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34522] [34523] [57803] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Dextromethorphan; Guaifenesin: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Dextromethorphan; Quinidine: (Contraindicated) Coadministration of quinidine (including dextromethorphan; quinidine) and eliglustat is contraindicated. Quinidine is a P-glycoprotein (P-gp) substrate and strong CYP2D6 inhibitor associated with a well-established risk of QT prolongation and torsades de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6. Eliglustat is a CYP2D6 substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinidine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [29376] [34452] [42280] [47357] [57803] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Digoxin: (Major) Coadministration of digoxin and eliglustat may result in increased digoxin concentrations, which may result in digoxin toxicity. Measure serum digoxin concentrations before initiating eliglustat, reduce the digoxin dose by 30%, and continue to monitor as clinically indicated. Eliglustat is a P-glycoprotein (P-gp) inhibitor, and digoxin is a P-gp substrate. During clinical trials, Cmax and AUC of digoxin increased by 1.7- and 1.5-fold, respectively, after multiple doses of eliglustat 127 mg PO twice daily in extensive and intermediate metabolizers or 84 mg PO twice daily in poor metabolizers. Of note, the only FDA-approved dose of eliglustat is 84 mg. [57803] Diltiazem: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of diltiazem and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both diltiazem and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Diltiazem is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as diltiazem, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [28277] [57803] Diphenhydramine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled diphenhydramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however coadministration of eliglustat with both diphenhydramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of diphenhydramine warrants modification of eliglustat therapy. Diphenhydramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as diphenhydramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single diphenhydramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., diphenhydramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34522] [34523] [57803] Diphenhydramine; Ibuprofen: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled diphenhydramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however coadministration of eliglustat with both diphenhydramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of diphenhydramine warrants modification of eliglustat therapy. Diphenhydramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as diphenhydramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single diphenhydramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., diphenhydramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34522] [34523] [57803] Diphenhydramine; Naproxen: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled diphenhydramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however coadministration of eliglustat with both diphenhydramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of diphenhydramine warrants modification of eliglustat therapy. Diphenhydramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as diphenhydramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single diphenhydramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., diphenhydramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34522] [34523] [57803] Diphenhydramine; Phenylephrine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of scheduled diphenhydramine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily during the course of antihistamine treatment; however coadministration of eliglustat with both diphenhydramine and a strong or moderate CYP3A inhibitor is contraindicated. It is unclear whether a single dose of diphenhydramine warrants modification of eliglustat therapy. Diphenhydramine is a substrate and moderate inhibitor of CYP2D6; eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as diphenhydramine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); the effects of a single diphenhydramine dose are unknown. In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., diphenhydramine) may result in increased concentrations of the concomitant drug; monitor patients closely for anticholinergic adverse events. [34522] [34523] [57803] Disopyramide: (Major) Coadministration of disopyramide and eliglustat is not recommended. If coadministration is necessary, use extreme caution and close monitoring. Disopyramide is associated with QT prolongation and torsades de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [28228] [57803] Docetaxel: (Major) Coadministration of docetaxel and eliglustat may result in increased plasma concentrations of docetaxel. If coadministration is necessary, use caution and monitor closely. Docetaxel is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [57803] [57949] Dofetilide: (Major) Coadministration of dofetilide and eliglustat is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28221] [28432] [28457] [57803] Dolasetron: (Moderate) Administer dolasetron with caution in combination with eliglustat as concurrent use may increase the risk of QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. [28308] [57803] Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with eliglustat as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [44376] [57803] Donepezil: (Moderate) Use donepezil with caution in combination with eliglustat. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [59321] [59322] Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with eliglustat. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [59321] [59322] Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] Dorzolamide; Timolol: (Moderate) Coadministration of timolol and eliglustat may result in increased plasma concentrations of timolol. Consider reducing the dosage of oral timolol and titrating to clinical effect. Timolol is a CYP2D6 substrate; eliglustat is a CYP2D6 inhibitor. [28540] [57803] Doxepin: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Doxorubicin Liposomal: (Major) Avoid coadministration of eliglustat with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Eliglustat is a CYP2D6 and P-glycoprotein (P-gp) inhibitor, and doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYP3A4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions. [34506] [57803] [61628] Doxorubicin: (Major) Avoid coadministration of eliglustat with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Eliglustat is a CYP2D6 and P-glycoprotein (P-gp) inhibitor, and doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYP3A4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions. [34506] [57803] [61628] Dronedarone: (Contraindicated) Coadministration of dronedarone and eliglustat is contraindicated. Dronedarone is a moderate CYP2D6 and CYP3A inhibitor associated with a dose-related increase in the QTc interval; its use is contraindicated with other drugs that prolong the QT interval. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of dronedarone and eliglustat may result in additive effects on the QT interval and signficantly increased plasma concentrations eliglustat, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [36101] [57803] Droperidol: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include droperidol. [28737] [57803] Duloxetine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of duloxetine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both duloxetine and a strong or moderate CYP3A inhibitor is contraindicated. Duloxetine is a CYP2D6 substrate and moderate inhibitor; eliglustat is a CYP2D6 and CYP3A substrate and a CYP2D6 inhibitor. Coadministration with CYP2D6 inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). In addition, coadministration of eliglustat with CYP2D6 substrates (e.g., duloxetine) may result in increased concentrations of the concomitant drug; monitor patients closely for adverse events, and consider reducing the dosage of duloxetine and titrating to clinical effect. [29934] [57803] Dutasteride; Tamsulosin: (Moderate) Coadministration of tamsulosin and eliglustat may result in increased concentrations of tamsulosin. Use tamsulosin with caution in patients receiving eliglustat, particularly if the tamsulosin dose is greater than 0.4 mg, and monitor closely for tamsulosin-related adverse effects including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 and CYP3A4 substrate; eliglustat is a CYP2D6 inhibitor. [29677] [57803] Duvelisib: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of duvelisib with eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of duvelisib and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both duvelisib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate; duvelisib is a moderate CYP3A inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as duvelisib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [57803] [63571] Edoxaban: (Moderate) Coadministration of edoxaban and eliglustat may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and eliglustat is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of eliglustat; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism. [57803] [58685] Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with eliglustat as concurrent use may increase the risk of QT prolongation; eliglustat exposure may also decrease. Efavirenz is a moderate CYP3A4 inducer; QTc prolongation has been observed with the use of efavirenz. Eliglustat is a CYP3A4 inducer that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28442] [57803] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] (Moderate) Consider alternatives to efavirenz when coadministering with eliglustat as concurrent use may increase the risk of QT prolongation; eliglustat exposure may also decrease. Efavirenz is a moderate CYP3A4 inducer; QTc prolongation has been observed with the use of efavirenz. Eliglustat is a CYP3A4 inducer that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28442] [57803] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] (Moderate) Consider alternatives to efavirenz when coadministering with eliglustat as concurrent use may increase the risk of QT prolongation; eliglustat exposure may also decrease. Efavirenz is a moderate CYP3A4 inducer; QTc prolongation has been observed with the use of efavirenz. Eliglustat is a CYP3A4 inducer that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28442] [57803] Elbasvir; Grazoprevir: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of grazoprevir and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Administering eliglustat with grazoprevir may result in elevated eliglustat plasma concentrations and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Eliglustat is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. [57803] [60523] Eletriptan: (Moderate) Coadministration of eletriptan and eliglustat may result in increased plasma concentrations of eletriptan. Monitor patients closely for eletriptan-related adverse effects. Eletriptan is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [57803] [57975] Elexacaftor; tezacaftor; ivacaftor: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ivacaftor and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Ivacaftor and its primary metabolite M1 are considered weak CYP3A inhibitors; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [48524] [57803] Eluxadoline: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of eluxadoline and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of eluxadoline and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Eluxadoline is a weak CYP3A4 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP3A4 inhibitors, such as eluxadoline, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [59741] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of eliglustat and cobicistat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with cobicistat and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as cobicistat, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. The product labeling for cobicistat states that coadministration of other drugs for which altered plasma concentrations are associated with serious and/or life-threatening effects is contraindicated; however, the interaction between ketoconazole (another potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. [28142] [32432] [34557] [57803] [57923] [58000] (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [57803] [57923] [60269] [60614] [60688] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of eliglustat and cobicistat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with cobicistat and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as cobicistat, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. The product labeling for cobicistat states that coadministration of other drugs for which altered plasma concentrations are associated with serious and/or life-threatening effects is contraindicated; however, the interaction between ketoconazole (another potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. [28142] [32432] [34557] [57803] [57923] [58000] (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [57803] [57923] [60269] [60614] [60688] (Moderate) Caution is advised when administering rilpivirine with eliglustat as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [44376] [57803] Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering rilpivirine with eliglustat as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [44376] [57803] (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [57803] [57923] [60269] [60614] [60688] Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] Enasidenib: (Moderate) Monitor for an increase in the frequency and severity of eliglustat-related adverse effects if concomitant use with enasidenib is necessary. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and enasidenib is a weak CYP2D6 inhibitor. [57803] [62181] Encorafenib: (Major) Avoid concurrent use of encorafenib with eliglustat due to the risk for decreased eliglustat exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Eliglustat is a CYP3A substrate, encorafenib is a strong CYP3A inducer, and both medications have been associated with QT/QTc prolongation. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in extensive metabolizers and intermediate metabolizers after coadministration of eliglustat 127 mg PO twice daily with another strong CYP3A inducer. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with another strong CYP3A inducer in poor metabolizers. [57803] [63317] Entrectinib: (Major) Avoid coadministration of entrectinib with eliglustat due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [64567] Enzalutamide: (Major) Coadministration of eliglustat and enzalutamide significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. Enzalutamide is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. [51727] [57803] Eribulin: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include eribulin. [42449] [57803] Erythromycin: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of erythromycin (including erythromycin; sulfisoxazole) and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of erythromycin and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both erythromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and erythromycin can independently prolong the QT interval, and coadministration increases this risk. Erythromycin is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as erythromycin, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [50528] [57803] Escitalopram: (Moderate) Concomitant use of escitalopram and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28270] [57803] Etrasimod: (Minor) QT/QTc prolongation can occur with concomitant use of etrasimod and eliglustat although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval. [57803] [69114] Everolimus: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of everolimus and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Everolimus is a weak CYP3A (and CYP2D6) inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [49598] [49823] [57803] Fedratinib: (Contraindicated) Coadministration of fedratinib and eliglustat is contraindicated in extensive or intermediate CYP2D6 metabolizers (EMs or IMs). Avoid coadministration in poor CYP2D6 metabolizers (PMs). In PMs also receiving a strong CYP3A4 inhibitor, coadministration is contraindicated. Eliglustat is a CYP3A and CYP2D6 substrate. Fedratinib is a moderate inhibitor of CYP3A4 and CYP2D6. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [57803] [64568] Fexinidazole: (Major) Concomitant use of fexinidazole and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, in extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; fexinidazole is a weak CYP3A inhibitor. [57803] [66812] Fingolimod: (Major) Coadministration of fingolimod and eliglustat is not recommended. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. If fingolimod must be coadministered with QT prolonging drugs with a known risk of torsade de pointes (TdP), overnight monitoring with continuous ECG in a medical facility is advised after the first fingolimod dose. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Overnight monitoring is also recommended if fingolimod therapy is interrupted 1 day or more during the first 2 weeks of fingolimod treatment, more than 7 days during the third and fourth week of treatment, and more than 14 days after the first month of treatment. [41823] [57803] Flecainide: (Major) Coadministration of flecainide and eliglustat may result in increased plasma concentrations of flecainide and an increased risk of QT prolongation. If concomitant use is necessary, monitor therapeutic flecainide concentrations as indicated; the dosage of flecainide may need to be reduced. Flecainide is a CYP2D6 substrate associated with a risk for QT prolongation and/or torsade de pointes (TdP). Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [51070] [57803] Fluconazole: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of fluconazole and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of fluconazole and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both fluconazole and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and fluconazole can independently prolong the QT interval, and coadministration increases this risk. Fluconazole is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as fluconazole, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Although fluconazole's product labeling states that coadministration of other drugs that prolong the QT interval and are metabolized by CYP3A4 is contraindicated, the specific interaction between fluconazole and eliglustat was studied during clinical trials and supports eliglustat dosage reduction in EMs instead of contraindication. Physiology-based pharmacokinetic (PBPK) models suggest that fluconazole may increase the Cmax and AUC of eliglustat 2.8- and 3.2-fold, respectively, in EMs and 2.5- and 2.9-fold, respectively, in IMs. PBPK suggests fluconazole may increase the Cmax and AUC of eliglustat 2.4- and 3-fold, respectively, when administered with eliglustat 84 mg PO once daily in PMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a moderate 2D6 inhibitor and fluconazole (moderate 3A4 inhibitor) may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs. [28227] [57803] Fluoxetine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of fluoxetine and eliglustat is not recommended. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), concurrent use of these agents requires dosage reduction of eliglustat to 84 mg PO once daily; monitor patients closely and consider reducing the dosage of fluoxetine and titrating to clinical effect. Coadministration of eliglustat with both fluoxetine and a strong or moderate CYP3A inhibitor is contraindicated in all patients. Fluoxetine is a substrate and strong inhibitor of CYP2D6 and a weak inhibitor of CYP3A that is independently associated with QT prolongation and torsade de pointes (TdP). Eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of fluoxetine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with even weak CYP3A inhibitors, such as fluoxetine, in this population may significantly increase eliglustat exposure and, hence, concurrent use is not recommended. [32127] [53347] [57803] Fluphenazine: (Minor) Coadministration of fluphenazine and eliglustat may result in increased concentrations of the phenothiazine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Consider reducing the dosage of phenothiazine and titrating to clinical effect. Fluphenazine is a CYP2D6 substrate associated with a possible risk for QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28415] [57803] Fluvoxamine: (Major) Fluvoxamine is a moderate CYP3A4 inhibitor and the manufacturer of eliglustat recommends against use with moderate CYP3A4 inhibitors due to the potential for increased eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 poor and intermediate metabolizers because a larger portion of the eliglustat dose is metabolized via CYP3A. In addition, QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of fluvoxamine which may further increase the risk of QT prolongation with eliglustat. Because eliglustat is a CYP2D6 inhibitor, coadministration with CYP2D6 substrates such as fluvoxamine may result in increased concentrations of the concomitant drug. If combination therapy cannot be avoided, monitor patients closely for adverse events, and use the lowest effective dosages of each drug. [50507] [57803] Fosamprenavir: (Major) Avoid coadministration of eliglustat with fosamprenavir in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate; fosamprenavir is a moderate inhibitor of CYP3A. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [29012] [57803] Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as eliglustat. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. [28377] [57803] Fosphenytoin: (Major) Coadministration of phenytoin or fosphenytoin and eliglustat may result in increased phenytoin concentrations and decreased eliglustat concentrations. Concomitant use is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. If concomitant use is necessary, monitor therapeutic phenytoin concentrations as indicated; the dosage of phenytoin may need to be reduced. Monitor patients closely for therapeutic effect of eliglustat. Eliglustat is a P-glycoprotein (P-gp) inhibitor and CYP3A substrate; phenytoin is a P-gp substrate and strong CYP3A inducer. [57803] Fostamatinib: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of fostamatinib and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Fostamatinib is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [57803] [63084] Fostemsavir: (Moderate) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation. [57803] [65666] Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with eliglustat is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and eliglustat is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism. [45935] [57803] Gemifloxacin: (Moderate) Gemifloxacin should be used cautiously with eliglustat as concurrent use may increase the risk of QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28424] [57803] Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and eliglustat together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [62292] Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and eliglustat is necessary. Gilteritinib has been associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [63787] Givosiran: (Major) Avoid concomitant use of givosiran and eliglustat due to the risk of increased eliglustat-related adverse effects (e.g., QT prolongation and cardiac arrhythmias). In poor CYP2D6 metabolizers (PMs), coadministration of givosiran and eliglustat is not recommended. If use is necessary, decrease the eliglustat dose. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both givosiran and a moderate or strong CYP3A inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and sensitive CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway. [57803] [64762] Glasdegib: (Major) Avoid coadministration of glasdegib with eliglustat due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [63777] Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and eliglustat as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor. [57803] [62201] (Moderate) Caution is advised with the coadministration of pibrentasvir and eliglustat as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); eliglustat is an inhibitor of P-gp. [57803] [62201] Glyburide: (Moderate) Coadministration of glyburide and eliglustat may result in increased plasma concentrations of glyburide. Monitor patients closely for glyburide-related adverse effects; if hypoglycemia occurs, consider reducing the glyburide dosage and titrating to clinical effect. Glyburide is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [34471] [57803] Glyburide; Metformin: (Moderate) Coadministration of glyburide and eliglustat may result in increased plasma concentrations of glyburide. Monitor patients closely for glyburide-related adverse effects; if hypoglycemia occurs, consider reducing the glyburide dosage and titrating to clinical effect. Glyburide is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [34471] [57803] Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28592] [57803] Granisetron: (Minor) Use granisetron with caution in combination with elglustat due to the risk of QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Granisetron has been associated with QT prolongation. [31723] [57803] Grapefruit juice: (Contraindicated) Avoid consumption of grapefruit or grapefruit juice with eliglustat. Grapefruit is a strong CYP3A inhibitor and eliglustat is a CYP3A substrate; consumption may increase exposure to eliglustat and increase the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] Halogenated Anesthetics: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include halogenated anesthetics. [57803] Haloperidol: (Major) Use great caution when coadministering haloperidol and eliglustat due to the risk of serious adverse events such as QT prolongation and cardiac arrhythmias. If concurrent use is necessary, consider reducing the dosage of haloperidol and titrating to clinical effect. Although haloperidol's impact on eliglustat is unclear, it may be prudent to reduce the eliglustat dosage to 84 mg PO once daily in extensive or intermediate CYP2D6 metabolizers (EMs or IMs). If eliglustat and haloperidol are taken together, concurrent use of a strong or moderate CYP3A inhibitor should be avoided. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations; it is also a CYP2D6 inhibitor. Haloperidol is primarily metabolized by CYP2D6; however, its inhibitory effects are unclear. Some pharmacokinetic data suggests that haloperidol may inhibit CYP2D6 and CYP3A4, while other data suggests the risk of clinically significant inhibition is low. Regardless, haloperidol has been associated with QT prolongation and torsade de pointes (TdP). Coadministration of haloperidol and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28225] [28307] [43715] [56382] [56383] [57203] [57803] Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [30369] [57803] Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with eliglustat may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of eliglustat could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If eliglustat is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Eliglustat is a moderate inhibitor of CYP2D6. [30379] [39926] [56303] [57803] Hydrocodone: (Moderate) Concomitant use of hydrocodone with eliglustat may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of eliglustat could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If eliglustat is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Eliglustat is a moderate inhibitor of CYP2D6. [30379] [39926] [56303] [57803] Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with eliglustat may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of eliglustat could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If eliglustat is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Eliglustat is a moderate inhibitor of CYP2D6. [30379] [39926] [56303] [57803] Hydroxychloroquine: (Major) Avoid coadministration of eliglustat and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [41806] [57803] [65157] [65170] Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [47129] [57803] Ibutilide: (Major) Coadministration of ibutilide and eliglustat is not recommended. If coadministration is necessary, use extreme caution and close monitoring. Ibutilide administration is associated with QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [41830] [57803] Idelalisib: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of idelalisib and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both idelalisib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Idelalisib is a strong CYP3A inhibitor and P-glycoprotein (P-gp) substrate in vitro; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as idelalisib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. In addition, because idelalisib is a P-gp substrate and eliglustat is a P-gp inhibitor, exposure to idelalisib may be increased; monitor patients closely for idelalisib-related adverse events, such as elevated liver transaminases, neutropenia, thrombocytopenia, and severe diarrhea. [57675] [57803] Iloperidone: (Major) Coadminister iloperidone and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or iloperidone-associated adverse effects. If coadministration is necessary, consider reducing the iloperidone dosage and titrating to clinical effect; although there are no specific dosage adjustment guidelines for coadministration with eliglustat, the iloperidone product label recommends decreasing the antipsychotic dose by one-half when used with a strong CYP2D6 inhibitor (e.g., fluoxetine). Eliglustat is CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Iloperidone is a CYP2D6 substrate independently associated with a risk of QT prolongation. Coadministration of iloperidone and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of iloperidone, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [36146] [57803] Imatinib: (Major) Coadministration of imatinib, STI-571 and eliglustat is contraindicated in extensive and intermediate CYP2D6 metabolizers (EMs or IMs) and not recommended in CYP26 poor metabolizers (PMs). Imatinib is an inhibitor of both CYP2D6 and CYP3A4. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of imatinib and eliglustat may result in significantly increased plasma concentrations of eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28240] [57803] Imipramine: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Indinavir: (Major) Coadministration of indinavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both indinavir and a moderate or strong CYP2D6 inhibitor, such as ritonavir, is contraindicated in all patients. Indinavir is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Although indinavir's product labeling states that coadministration of certain CYP3A substrates that have the potential for serious adverse events with elevated concentrations are contraindicated, the interaction between ketoconazole (a potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. In addition, because indinavir is a P-gp substrate and eliglustat is a P-gp inhibitor, exposure to indinavir may be increased; monitor patients closely for indinavir-related adverse events, including gastrointestinal and renal symptoms. [28731] [34557] [57803] Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with eliglustat due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [62245] Isavuconazonium: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of isavuconazonium with eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of isavuconazonium and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both isavuconazonium and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as isavuconazole, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [57803] [59042] Isoflurane: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include halogenated anesthetics. [57803] Isoniazid, INH: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of isoniazid and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Isoniazid ia a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [57803] [63701] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of eliglustat and rifampin significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6 (EMs, IMs, PMs). Rifampin is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with rifampin 600 mg PO once daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs. [57803] (Major) In poor CYP2D6 metabolizers (PMs), coadministration of isoniazid and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Isoniazid ia a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [57803] [63701] Isoniazid, INH; Rifampin: (Major) Coadministration of eliglustat and rifampin significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6 (EMs, IMs, PMs). Rifampin is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with rifampin 600 mg PO once daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs. [57803] (Major) In poor CYP2D6 metabolizers (PMs), coadministration of isoniazid and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Isoniazid ia a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [57803] [63701] Istradefylline: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of istradefylline 40 mg daily and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate. [57803] [64590] Itraconazole: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), eliglustat is contraindicated for use during and for 2 weeks after itraconazole therapy; recommendations for extensive CYP2D6 metabolizers (EMs) is less clear. In addition, use of eliglustat with a moderate or strong CYP2D6 inhibitor is contraindicated for use during and for 2 weeks after itraconazole therapy in all patients (i.e., IMs, PMs, and EMs). Both eliglustat and itraconazole can independently prolong the QT interval. Itraconazole is a strong CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Both drugs have the potential to increase each other's blood concentrations, and therefore, further increase the risk of QT prolongation. Itraconazole's product labeling contraindicates coadministration of a number of other drugs that prolong the QT interval and are metabolized by CYP3A4. The product labeling of ketoconazole (another systemic azole and strong CYP3A inhibitor) carries the same contraindication, but pharmacokinetic data examining the interaction between ketoconazole and eliglustat support a dose reduction of eliglustat to 84 mg PO once daily in EMs rather than contraindication. However, extrapolation of this data to itraconazole must be undertaken with extreme caution because itraconazole is a P-gp substrate (ketoconazole is not), and eliglustat is a P-gp inhibitor. The additional risk that increased itraconazole exposure could pose is not known. [27983] [40233] [57803] Ivacaftor: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ivacaftor and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Ivacaftor and its primary metabolite M1 are considered weak CYP3A inhibitors; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [48524] [57803] Ivosidenib: (Major) Avoid coadministration of ivosidenib with eliglustat due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [63368] Ketoconazole: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of ketoconazole and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both ketoconazole and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and ketoconazole can independently prolong the QT interval, and coadministration increases this risk. Ketoconazole is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Although ketoconazole's product labeling states that coadministration of other drugs that prolong the QT interval and are metabolized by CYP3A4 is contraindicated, the specific interaction between ketoconazole and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. During clinical trials in EMs (n = 31), Cmax and AUC increased 4-fold and 4.4-fold, respectively, after co-administration of eliglustat 84 mg PO twice daily with ketoconazole 400 mg once daily. Physiology-based pharmacokinetic (PBPK) models suggest that ketoconazole may increase the Cmax and AUC of eliglustat 4.4- and 5.4-fold, respectively, in IMs. PBPK suggests ketoconazole may increase the Cmax and AUC of eliglustat 4.3- and 6.2-fold, respectively, when administered with eliglustat 84 mg PO once daily in PMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a strong 2D6 inhibitor and ketoconazole (strong 3A4 inhibitor) may increase the Cmax and AUC of eliglustat 16.7- and 24.2-fold, respectively, in EMs and 7.5- and 9.8-fold, respectively, in IMs. [27982] [57803] Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] Lansoprazole; Amoxicillin; Clarithromycin: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of clarithromycin and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both clarithromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and clarithromycin can independently prolong the QT interval, and coadministration increases this risk. Clarithromycin is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors such as clarithromycin increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [25238] [28225] [57803] Lapatinib: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of lapatinib and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. These agents should be used concomitantly with caution in any patient. Monitor for QT prolongation and torsade de pointes (TdP). Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Lapatinib is a weak CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may significantly increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [33192] [57803] Larotrectinib: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of larotrectinib and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Larotrectinib ia a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [63780] Lefamulin: (Major) Avoid coadministration of lefamulin with eliglustat as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets and eliglustat which may increase the risk of adverse effects. If coadministration cannot be avoided, monitor ECG during treatment. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Lefamulin is a moderate CYP3A4 inhibitor and CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Eliglustat is CYP3A4 and CYP2D6 substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [64576] Lenacapavir: (Major) Avoid coadministration of eliglustat with lenacapavir in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate; lenacapavir is a moderate inhibitor of CYP3A. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [57803] [68383] Lenvatinib: (Major) Avoid coadministration of lenvatinib with eliglustat due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [58782] Letermovir: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of letermovir and eliglustat is not recommended; this combination is contraindicated in this population if the patient is also receiving cyclosporine. In extensive CYP2D6 metabolizers (EMs), coadministration of letermovir and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both letermovir and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Letermovir is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. The magnitude of this interaction may be further amplified in patients receiving concurrent treatment with cyclosporine, as the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. [57803] [62611] Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [43800] [57803] Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [43800] [57803] Levamlodipine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Levofloxacin: (Moderate) Concomitant use of levofloxacin and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28421] [57803] Levoketoconazole: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of ketoconazole and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both ketoconazole and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and ketoconazole can independently prolong the QT interval, and coadministration increases this risk. Ketoconazole is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Although ketoconazole's product labeling states that coadministration of other drugs that prolong the QT interval and are metabolized by CYP3A4 is contraindicated, the specific interaction between ketoconazole and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. During clinical trials in EMs (n = 31), Cmax and AUC increased 4-fold and 4.4-fold, respectively, after co-administration of eliglustat 84 mg PO twice daily with ketoconazole 400 mg once daily. Physiology-based pharmacokinetic (PBPK) models suggest that ketoconazole may increase the Cmax and AUC of eliglustat 4.4- and 5.4-fold, respectively, in IMs. PBPK suggests ketoconazole may increase the Cmax and AUC of eliglustat 4.3- and 6.2-fold, respectively, when administered with eliglustat 84 mg PO once daily in PMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a strong 2D6 inhibitor and ketoconazole (strong 3A4 inhibitor) may increase the Cmax and AUC of eliglustat 16.7- and 24.2-fold, respectively, in EMs and 7.5- and 9.8-fold, respectively, in IMs. [27982] [57803] Lithium: (Major) Lithium should be used cautiously and with close monitoring with eliglustat. Lithium has been associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [59809] [59810] [59811] Lofexidine: (Major) Monitor the ECG for QT prolongation during concurrent use of lofexidine and eliglustat. Lofexidine may prolong the QT interval, and torsade de pointes (TdP) has been reported during postmarketing use. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [63161] Lonafarnib: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of lonafarnib and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both lonafarnib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate and lonafarnib is a strong CYP3A inhibitor. Coadministration of eliglustat with CYP3A inhibitors such as lonafarnib increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [57803] [66129] Loperamide: (Moderate) Concomitant use of loperamide and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and eliglustat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold. [33607] [57803] Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and eliglustat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold. [33607] [57803] Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with eliglustat due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28341] [57803] [65157] [65170] (Major) Coadministration of eliglustat and ritonavir is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with ritonavir and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as ritonavir, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [28341] [47165] [57803] Lorcaserin: (Moderate) Monitor for an increase in the frequency and severity of eliglustat-related adverse effects if concomitant use with lorcaserin is necessary. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and lorcaserin is a weak CYP2D6 inhibitor. [51065] [57803] Lumacaftor; Ivacaftor: (Major) Coadministration of eliglustat and lumacaftor; ivacaftor significantly decreases eliglustat exposure; coadministration is not recommended in patients of any metabolizer status. Lumacaftor is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with another strong CYP3A inducer, rifampin 600 mg PO once daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs. Eliglustat is also a substrate of the drug transporter P-glycoprotein (P-gp), and in vitro data suggests lumacaftor; ivacaftor may induce and/or inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear. [57803] [59891] (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ivacaftor and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Ivacaftor and its primary metabolite M1 are considered weak CYP3A inhibitors; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [48524] [57803] Lumacaftor; Ivacaftor: (Major) Coadministration of eliglustat and lumacaftor; ivacaftor significantly decreases eliglustat exposure; coadministration is not recommended in patients of any metabolizer status. Lumacaftor is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with another strong CYP3A inducer, rifampin 600 mg PO once daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs. Eliglustat is also a substrate of the drug transporter P-glycoprotein (P-gp), and in vitro data suggests lumacaftor; ivacaftor may induce and/or inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear. [57803] [59891] Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as eliglustat. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [62723] Maprotiline: (Major) Coadminister maprotiline and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and maprotiline are used together, consider reducing the dosage of maprotiline and titrating to clinical effect. Eliglustat is a CYP2D6 inhibitor, and maprotiline is a CYP2D6 substrate. [28225] [28759] [57803] Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and eliglustat as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); eliglustat is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible. [33473] [57803] Maribavir: (Major) Coadministration of eliglustat and maribavir is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Maribavir is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67137] Mefloquine: (Major) Coadminister mefloquine and eliglustat cautiously with close monitoring; there may be an increased risk of QT prolongation and/or mefloquine-associated adverse effects. Although mefloquine alone has not been reported to cause QT prolongation, there is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Due to the lack of clinical data and the potential for torsade de pointes (TdP), mefloquine should be used with caution in patients receiving other drugs that prolong the QT interval, such as eliglustat. In addition, coadministration of mefloquine, a P-glycoprotein (P-gp) substrate, and eliglustat, a P-gp inhibitor, may result in increased concentrations of mefloquine, further increasing the risk of adverse effects (e.g., QT prolongation and cardiac arrhythmias). [28301] [34450] [57803] Methadone: (Major) Coadministration of methadone and eliglustat may result in increased opioid plasma concentrations and an increased risk for QT prolongation. If coadministration is necessary, use great caution and monitor patients closely at frequent intervals. Consider reducing the dosage of methadone until stable drug effects are achieved, and titrating to clinical effect. Eliglustat is a CYP2D6 and P-glycoprotein (P-gp) inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Although methadone is primarily metabolized by other CYP450 isoenzymes (i.e., CYP3A4, CYP2B6, CYP2C19), it is metabolized to a lesser extent by CYP2D6 and is considered a P-gp substrate. In addition, methadone is independently associated with a risk for QT prolongation and torsade de pointes (TdP). Coadministration of methadone and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of methadone, further increasing the risk of serious adverse events (e.g., respiratory depression, sedation, QT prolongation, cardiac arrhythmias). [32532] [33136] [57803] Methamphetamine: (Major) Coadministration of methamphetamine and eliglustat may result in increased plasma concentrations of methamphetamine. If coadministration is necessary, monitor patients closely methamphetamine toxicity (e.g., restlessness, tremor, tachypnea, confusion, panic states, rhabdomyolysis). Methamphetamine is a CYP2D6 substrate; eliglustat is a CYP2D6 inhibitor. [33363] [57067] [57803] Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; eliglustat is a moderate CYP2D6 inhibitor. During clinical trials, the Cmax and AUC of metoprolol increased by 1.7- and 2.3-fold, respectively, in extensive metabolizers and 1.2- and 1.6-fold, respectively, in intermediate metabolizers after multiple doses of eliglustat 127 mg PO twice daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. [32916] [57803] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; eliglustat is a moderate CYP2D6 inhibitor. During clinical trials, the Cmax and AUC of metoprolol increased by 1.7- and 2.3-fold, respectively, in extensive metabolizers and 1.2- and 1.6-fold, respectively, in intermediate metabolizers after multiple doses of eliglustat 127 mg PO twice daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. [32916] [57803] Metronidazole: (Moderate) Concomitant use of metronidazole and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [36894] [57803] Mexiletine: (Major) Coadministration of mexiletine and eliglustat may result in increased concentrations of mexiletine, which has a narrow therapeutic index; use these drugs together with extreme caution. If coadministration is necessary, titrate the mexiletine dose slowly to the desired clinical effect and monitor patients closely for mexiletine-related adverse effects such as cardiac arrhythmias. Mexiletine is a CYP2D6 substrate, and eliglustat is a CYP2D6 inhibitor. [28280] [57803] Midostaurin: (Major) The concomitant use of midostaurin and eliglustat may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [61906] Mifepristone: (Major) Concomitant use of eliglustat and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [48697] [57803] Mirabegron: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of mirabegron and eliglustat is not recommended. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both mirabegron and a moderate or strong CYP3A inhibitor is contraindicated in all patients. Mirabegron is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as mirabegron, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [51111] [57803] Mirtazapine: (Major) Concomitant use of eliglustat and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [40942] [57803] Mitotane: (Major) The concomitant use of mitotane with eliglustat is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6 (EMs, IMs, PMs). Mitotane is a strong CYP3A4 inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with another strong CYP3A inducer, rifampin (600 mg PO daily). Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs. [41934] [57803] Mobocertinib: (Major) Concomitant use of mobocertinib and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [57803] [66990] Morphine: (Minor) Coadministration of morphine and eliglustat may result in increased plasma concentrations of morphine. Monitor patients closely for morphine-related adverse effects including respiratory depression, and consider reducing the morphine dosage and titrating to clinical effect. Morphine is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [34448] [57803] Morphine; Naltrexone: (Minor) Coadministration of morphine and eliglustat may result in increased plasma concentrations of morphine. Monitor patients closely for morphine-related adverse effects including respiratory depression, and consider reducing the morphine dosage and titrating to clinical effect. Morphine is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [34448] [57803] Moxifloxacin: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include moxifloxacin. [28423] [57803] Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with eliglustat. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a P-gp substrate; eliglustat is a moderate P-gp inhibitor. [57803] [61831] Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and eliglustat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and eliglustat is a P-gp inhibitor. [57803] [67136] Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with eliglustat. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as eliglustat, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. Consider reducing the dosage of nebivolol and titrating to clinical effect. [57803] [60860] [60986] [60987] Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with eliglustat. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as eliglustat, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. Consider reducing the dosage of nebivolol and titrating to clinical effect. [57803] [60860] [60986] [60987] Nefazodone: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of nefazodone and eliglustat is contraindicated. In extensive CYP2D6 metabolizer (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both nefazodone and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Nefazodone is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as nefazodone, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [28683] [54634] [57803] Nelfinavir: (Major) Coadministration of nelfinavir and eliglustat is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both nelfinavir and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Nelfinavir is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Although nelfinavir's product labeling states that coadministration of other drugs that are highly dependent on CYP3A for metabolic clearance and have the potential for serious adverse events with elevated concentrations are contraindicated, the interaction between ketoconazole (a potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. In addition, because nelfinavir is a P-glycoprotein (P-gp) substrate and eliglustat is a P-gp inhibitor, exposure to nelfinavir may be increased; monitor patients closely for nelfinavir-related adverse events. [28839] [34558] [34559] [57803] Nicardipine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of nicardipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of nicardipine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Nicardipine is a CYP3A4 and CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP3A4 and CYP2D6 inhibitors, such as nicardipine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [53823] [57803] Nilotinib: (Major) Avoid the concomitant use of nilotinib and eliglustat; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [58766] Niraparib; Abiraterone: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of abiraterone and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both abiraterone and a strong or moderate CYP3A inhibitor is contraindicated. Abiraterone is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration with CYP2D6 inhibitors, such as abiraterone, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Physiology-based pharmacokinetic (PBPK) models suggest that another moderate CYP2D6 inhibitor may increase the Cmax and AUC of eliglustat 3.8- and 4.5-fold, respectively, in EMs and 1.6-fold (both Cmax and AUC) in IMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a moderate 2D6 inhibitor and a moderate 3A4 inhibitor may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs. [44156] [57803] Nirmatrelvir; Ritonavir: (Major) Coadministration of eliglustat and ritonavir is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with ritonavir and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as ritonavir, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [28341] [47165] [57803] Nirogacestat: (Major) Avoid coadministration of eliglustat with nirogacestat in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate; nirogacestat is a moderate inhibitor of CYP3A. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [57803] [69917] Nortriptyline: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Ofloxacin: (Moderate) Concomitant use of ofloxacin and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [30738] [57803] Olanzapine: (Major) Coadminister olanzapine and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or olanzapine-associated adverse effects. If coadministration is necessary, olanzapine dosage reduction may be considered but is not routinely recommended. Eliglustat is CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Olanzapine is a minor substrate of CYP2D6 in vivo. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Coadministration of olanzapine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of olanzapine, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28785] [32732] [32734] [32745] [32746] [57803] Olanzapine; Fluoxetine: (Major) Coadminister olanzapine and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or olanzapine-associated adverse effects. If coadministration is necessary, olanzapine dosage reduction may be considered but is not routinely recommended. Eliglustat is CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Olanzapine is a minor substrate of CYP2D6 in vivo. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Coadministration of olanzapine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of olanzapine, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28785] [32732] [32734] [32745] [32746] [57803] (Major) In poor CYP2D6 metabolizers (PMs), coadministration of fluoxetine and eliglustat is not recommended. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), concurrent use of these agents requires dosage reduction of eliglustat to 84 mg PO once daily; monitor patients closely and consider reducing the dosage of fluoxetine and titrating to clinical effect. Coadministration of eliglustat with both fluoxetine and a strong or moderate CYP3A inhibitor is contraindicated in all patients. Fluoxetine is a substrate and strong inhibitor of CYP2D6 and a weak inhibitor of CYP3A that is independently associated with QT prolongation and torsade de pointes (TdP). Eliglustat is a substrate and inhibitor of CYP2D6 and a CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of fluoxetine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with even weak CYP3A inhibitors, such as fluoxetine, in this population may significantly increase eliglustat exposure and, hence, concurrent use is not recommended. [32127] [53347] [57803] Olanzapine; Samidorphan: (Major) Coadminister olanzapine and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or olanzapine-associated adverse effects. If coadministration is necessary, olanzapine dosage reduction may be considered but is not routinely recommended. Eliglustat is CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Olanzapine is a minor substrate of CYP2D6 in vivo. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Coadministration of olanzapine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of olanzapine, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28785] [32732] [32734] [32745] [32746] [57803] Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and eliglustat is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and eliglustat may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If eliglustat is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and eliglustat is a moderate CYP2D6 inhibitor. [57803] [65809] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Ondansetron: (Major) Coadminister ondansetron and eliglustat cautiously with close monitoring; there may be an increased risk of QT prolongation and/or ondansetron-associated adverse effects. Ondansetron dosage reduction may be considered, depending on the clinical situation. Eliglustat is a CYP2D6 and P-glycoprotein (P-gp) inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Although ondansetron is primarily metabolized by other CYP450 isoenzymes (i.e., CYP3A4 and CYP1A2), it is metabolized to a lesser extent by CYP2D6 and is considered a P-gp substrate. In addition, ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). [31266] [34653] [49444] [57803] Osilodrostat: (Major) Coadministration of eliglustat and osilodrostat is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Osilodrostat is a weak CYP3A4 and CYP2D6 inhibitor; eliglustat is a CYP3A4 and CYP2D6 substrate. Because CYP3A4 plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A4 inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [65098] Osimertinib: (Major) Avoid coadministration of eliglustat with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [60297] Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of eliglustat with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. [41958] [57803] Ozanimod: (Major) In general, do not initiate ozanimod in patients taking eliglustat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [65169] Pacritinib: (Major) Concomitant use of eliglustat and pacritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase eliglustat exposure and the risk for other eliglustat-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Coadministration of eliglustat and pacritinib is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Pacritinib is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67427] Palbociclib: (Major) Coadministration of palbociclib, a weak CYP3A4 inhibitor, and eliglustat, a CYP2D6 and CYP3A4 substrate, is not recommended in patients who are CYP2D6 poor metabolizers. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Monitor for an increase in eliglustat-related adverse reactions during concurrent use of palbociclib in CYP2D6 intermediate and extensive metabolizers. Increased exposure to eliglustat could result in prolongation of the PR, QTc, and/or QRS cardiac interval, which could result in cardiac arrhythmias. [57803] [58768] [64721] Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. [40936] [57803] Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include eliglustat. [57803] [58821] Paroxetine: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving paroxetine. Eliglustat is contraindicated in EMs and IMs who are receiving paroxetine plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving paroxetine plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving paroxetine plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Also, monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with eliglustat is necessary. Concomitant use may increase paroxetine exposure. Eliglustat is a substrate and moderate inhibitor of CYP2D6 and paroxetine is a substrate and strong inhibitor of CYP2D6. A strong CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 8.4-fold and 2.3-fold in extensive and intermediate metabolizers, respectively. Strong CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs). [28260] [57803] Pasireotide: (Moderate) Use caution when using pasireotide in combination with eliglustat as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [52611] [57803] Pazopanib: (Major) Coadministration of pazopanib and eliglustat is not recommended. Eliglustat is a CYP2D6 and CYP3A4 substrate predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations; it is also a P-glycoprotein (P-gp) inhibitor. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6 in vivo and a P-gp substrate in vitro; it can also independently prolong the QT interval. Coadministration of eliglustat and pazopanib may result in additive effects on the QT interval and, potentially, increased plasma concentrations of both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [37098] [57803] Peginterferon Alfa-2b: (Moderate) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of peginterferon alfa-2b and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both peginterferon alfa-2b and a strong or moderate CYP3A inhibitor is contraindicated. Peginterferon alfa-2b is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration with CYP2D6 inhibitors, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Physiology-based pharmacokinetic (PBPK) models suggest that peginterferon alfa-2b may increase the Cmax and AUC of eliglustat 3.8- and 4.5-fold, respectively, in EMs and 1.6-fold (both Cmax and AUC) in IMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a moderate 2D6 inhibitor and a moderate 3A4 inhibitor may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs. [29627] [43887] [57803] Pentamidine: (Major) Coadministration of systemic pentamidine and eliglustat may result in increased concentrations of pentamidine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Systemic pentamidine has been associated with QT prolongation. In addition, data from healthy volunteers has shown that pentamidine metabolism is mediated in part by CYP2D6. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [23620] [23778] [28419] [28879] [34463] [57803] Perindopril; Amlodipine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Perphenazine: (Minor) Coadministration of perphenazine and eliglustat may result in increased concentrations of the phenothiazine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Consider reducing the dosage of phenothiazine and titrating to clinical effect. Perphenazine is a CYP2D6 substrate associated with a possible risk for QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28415] [57803] Perphenazine; Amitriptyline: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] (Minor) Coadministration of perphenazine and eliglustat may result in increased concentrations of the phenothiazine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Consider reducing the dosage of phenothiazine and titrating to clinical effect. Perphenazine is a CYP2D6 substrate associated with a possible risk for QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28415] [57803] Phenobarbital: (Major) Coadministration of eliglustat and phenobarbital significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. Phenobarbital is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. [57803] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of eliglustat and phenobarbital significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. Phenobarbital is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. [57803] Phenytoin: (Major) Coadministration of phenytoin or fosphenytoin and eliglustat may result in increased phenytoin concentrations and decreased eliglustat concentrations. Concomitant use is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. If concomitant use is necessary, monitor therapeutic phenytoin concentrations as indicated; the dosage of phenytoin may need to be reduced. Monitor patients closely for therapeutic effect of eliglustat. Eliglustat is a P-glycoprotein (P-gp) inhibitor and CYP3A substrate; phenytoin is a P-gp substrate and strong CYP3A inducer. [57803] Pimavanserin: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Because pimavanserin may also cause QT prolongation, coadministration should generally be avoided. [57803] [60748] Pimozide: (Contraindicated) Coadministration of pimozide and eliglustat is contraindicated. Pimozide is a CYP2D6 substrate associated with a well-established risk of QT prolongation and torsade de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and drugs that are strong CYP2D6 inhibitors. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of pimozide and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations pimozide, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28225] [43463] [57803] Pirtobrutinib: (Major) Coadministration of eliglustat and pirtobrutinib is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; pirtobrutinib is a weak CYP3A inhibitor. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [68520] Pitolisant: (Major) Avoid coadministration of pitolisant with eliglustat as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [64562] Ponesimod: (Major) In general, do not initiate ponesimod in patients taking eliglustat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [66527] Posaconazole: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of posaconazole and eliglustat is contraindicated; recommendations for extensive CYP2D6 metabolizers (EMs) is less clear. Both eliglustat and posaconazole can independently prolong the QT interval. Posaconazole is a strong CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Both drugs have the potential to increase each other's blood concentrations, and therefore, further increase the risk of QT prolongation. Posaconazole's product labeling contraindicates coadministration of a number of other drugs that prolong the QT interval and are metabolized by CYP3A4. The product labeling of ketoconazole (another systemic azole and strong CYP3A inhibitor) carries the same contraindication, but pharmacokinetic data examining the interaction between ketoconazole and eliglustat support a dose reduction of eliglustat to 84 mg PO once daily in EMs rather than contraindication. However, extrapolation of this data to posaconazole must be undertaken with extreme caution because posaconazole is a P-gp substrate (ketoconazole is not), and eliglustat is a P-gp inhibitor. The additional risk that increased posaconazole exposure could pose is not known. The coadministration of eliglustat with both posaconazole and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. [32723] [57803] Pralsetinib: (Major) Avoid concomitant use of eliglustat with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and eliglustat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%. [57803] [65884] Primaquine: (Moderate) Exercise caution when administering primaquine in combination with eliglustat as concurrent use may increase the risk of QT prolongation. Primaquine is associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [41984] [57803] Primidone: (Major) Coadministration of eliglustat and primidone significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. Primidone is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. [57046] [57048] [57803] Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and eliglustat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and eliglustat is a P-gp inhibitor. [36114] [57803] [58111] [63965] [69117] Procainamide: (Major) Coadministration of procainamide and eliglustat is not recommended. If coadministration is necessary, use extreme caution and close monitoring. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [28225] [28250] [57803] Prochlorperazine: (Minor) Coadministration of prochlorperazine and eliglustat may result in increased concentrations of the phenothiazine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Consider reducing the dosage of phenothiazine and titrating to clinical effect. Prochlorperazine is a CYP2D6 substrate associated with a possible risk for QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28415] [57803] Promethazine: (Major) Coadministration of promethazine and eliglustat may result in increased concentrations of the phenothiazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of promethazine and titrating to clinical effect. Promethazine is a CYP2D6 substrate associated with a possible risk of QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28225] [55578] [57803] Promethazine; Dextromethorphan: (Major) Coadministration of promethazine and eliglustat may result in increased concentrations of the phenothiazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of promethazine and titrating to clinical effect. Promethazine is a CYP2D6 substrate associated with a possible risk of QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28225] [55578] [57803] (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. [42280] [56579] [57803] [61317] Promethazine; Phenylephrine: (Major) Coadministration of promethazine and eliglustat may result in increased concentrations of the phenothiazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of promethazine and titrating to clinical effect. Promethazine is a CYP2D6 substrate associated with a possible risk of QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28225] [55578] [57803] Propafenone: (Major) Coadministration of propafenone and eliglustat may result in a complex drug interaction that increases the risk of QT prolongation and cardiac arrhythmias; coadministration must be approached with extreme caution and careful patient selection. Coadministration of eliglustat with both propafenone and a CYP3A inhibitor is contraindicated. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration requires dosage reduction of eliglustat to 84 mg PO once daily. In addition, consider reducing the dosage of propafenone and titrate to clinical effect with careful monitoring. Coadministration can increase plasma concentrations of either or both drugs. Propafenone is a CYP2D6 substrate and moderate CYP2D6 inhibitor that can increase the QT interval. Eliglustat is a CYP2D6 inhibitor and a substrate of CYP2D6 and CYP3A that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28287] [57803] Propranolol: (Moderate) Coadministration of propranolol and eliglustat may result in increased plasma concentrations of propranolol. Consider reducing the propranolol dosage and titrating to clinical effect. Propranolol is a CYP2D6 and P-glycoprotein (P-gp) substrate; eliglustat is a CYP2D6 and P-gp inhibitor. [53617] [57803] Protriptyline: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Quetiapine: (Major) Concomitant use of quetiapine and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [33068] [33072] [33074] [57803] Quinidine: (Contraindicated) Coadministration of quinidine (including dextromethorphan; quinidine) and eliglustat is contraindicated. Quinidine is a P-glycoprotein (P-gp) substrate and strong CYP2D6 inhibitor associated with a well-established risk of QT prolongation and torsades de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6. Eliglustat is a CYP2D6 substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinidine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [29376] [34452] [42280] [47357] [57803] Quinine: (Contraindicated) Coadministration of quinine and eliglustat is contraindicated. Quinine is a CYP2D6 and CYP3A4 inhibitor associated with QT prolongation and rare cases of torsade de points (TdP); its use should be avoided with other drugs that prolong the QT interval. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinine and eliglustat may result in additive effects on the QT interval and significantly increased plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [31403] [34335] [57803] Quizartinib: (Major) Concomitant use of quizartinib and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [57803] [69220] Ranitidine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ranitidine and eliglustat is not recommended. Ranitidine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [57803] Ranolazine: (Major) Coadminister ranolazine and eliglustat with caution. Based on in vitro pharmacokinetic data, coadministration is not recommended in CYP2D6 poor metabolizers (PMs) and a dosage reduction of eliglustat to 84 mg PO once daily is required in extensive or intermediate CYP2D6 metabolizers (EMs or IMs). In addition, coadministration of eliglustat with both ranolazine and a strong or moderate CYP3A inhibitor is contraindicated in all patients. Both eliglustat and ranolazine can independently prolong the QT interval, and coadministration increases this risk. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. In vitro data indicate ranolazine is a CYP2D6 and P-glycoprotein (P-gp) substrate, as well as a weak inhibitor of CYP3A and moderate inhibitor of CYP2D6. Eliglustat is a CYP2D6 and CYP3A substrate and CYP2D6 and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of ranolazine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). For coadministration with P-gp substrates and CYP2D6 substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [31938] [57803] Relugolix: (Major) Avoid concomitant use of relugolix and oral eliglustat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer eliglustat at least 6 hours after relugolix and monitor for adverse reactions. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Relugolix is a P-gp substrate and eliglustat is a P-gp inhibitor. [57803] [66183] Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral eliglustat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer eliglustat at least 6 hours after relugolix and monitor for adverse reactions. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Relugolix is a P-gp substrate and eliglustat is a P-gp inhibitor. [57803] [66183] Repotrectinib: (Major) Avoid coadministration of repotrectinib with eliglustat due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a P-gp substrate and eliglustat is a P-gp inhibitor. [57803] [69884] Ribociclib: (Major) Avoid coadministration of eliglustat with ribociclib due to the risk of QT prolongation. Coadministration is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs), and when concomitantly used with a moderate or strong CYP2D6 inhibitor in all patients. Eliglustat is a CYP3A4 and CYP2D6 substrate that causes PR, QRS, and QT prolongation at elevated plasma concentrations; the risk is highest in CYP2D6 IMs and PMs because a larger portion of the dose is metabolized via CYP3A. Ribociclib is a strong CYP3A4 inhibitor that is also associated with concentration-dependent QT prolongation. [57803] [61816] Ribociclib; Letrozole: (Major) Avoid coadministration of eliglustat with ribociclib due to the risk of QT prolongation. Coadministration is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs), and when concomitantly used with a moderate or strong CYP2D6 inhibitor in all patients. Eliglustat is a CYP3A4 and CYP2D6 substrate that causes PR, QRS, and QT prolongation at elevated plasma concentrations; the risk is highest in CYP2D6 IMs and PMs because a larger portion of the dose is metabolized via CYP3A. Ribociclib is a strong CYP3A4 inhibitor that is also associated with concentration-dependent QT prolongation. [57803] [61816] Rifampin: (Major) Coadministration of eliglustat and rifampin significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6 (EMs, IMs, PMs). Rifampin is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in EMs and IMs after coadministration of eliglustat 127 mg PO twice daily with rifampin 600 mg PO once daily. Of note, the only FDA-approved dose of eliglustat is 84 mg. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with rifampin 600 mg PO once daily in PMs. [57803] Rifapentine: (Major) Avoid coadministration of eliglustat and rifapentine as concurrent use may decrease eliglustat exposure and lead to reduced efficacy. Eliglustat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in extensive metabolizers and intermediate metabolizers after coadministration of eliglustat 127 mg PO twice daily with another strong CYP3A inducer. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with another strong CYP3A inducer in poor metabolizers. [57803] [65685] Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with eliglustat is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and eliglustat is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold. [29289] [57803] Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with eliglustat as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [44376] [57803] Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with eliglustat; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and eliglustat is a P-gp inhibitor. [57803] [65052] Risperidone: (Moderate) Use risperidone and eliglustat together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28414] [57803] Ritlecitinib: (Major) Avoid coadministration of eliglustat with ritlecitinib in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate; ritlecitinib is a moderate inhibitor of CYP3A. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [57803] [69127] Ritonavir: (Major) Coadministration of eliglustat and ritonavir is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with ritonavir and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as ritonavir, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [28341] [47165] [57803] Rivaroxaban: (Moderate) Coadministration of rivaroxaban and eliglustat may increase exposure to rivaroxaban and increase the risk of bleeding; monitor patients closely. Rivaroxaban is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [44854] [57803] Rolapitant: (Major) Use caution if eliglustat and rolapitant are used concurrently, and monitor for eliglustat-related adverse effects. Eliglustat is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured. [57803] [60142] Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with eliglustat. Romidepsin has been reported to prolong the QT interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [37292] [57803] Rucaparib: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of rucaparib and eliglustat is not recommended. Rucaparib is a weak CYP3A inhibitor; eliglustat is a CYP3A substrate. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [57803] [61608] Saquinavir: (Contraindicated) Coadministration of saquinavir and eliglustat is contraindicated. Saquinavir is a P-glycoprotein (P-gp) substrate and strong CYP3A inhibitor that, when boosted with ritonavir, prolongs the QT and PR interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and CYP3A substrates for which increased plasma concentrations may result in serious reactions. Eliglustat is a CYP3A substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of saquinavir and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28995] [57803] Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with eliglustat is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [65387] Sertraline: (Moderate) Concomitant use of sertraline and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose. [28343] [57803] [64391] [64392] [64394] [64395] [64396] Sevoflurane: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include halogenated anesthetics. [57803] Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving eliglustat due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [64031] Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of eliglustat. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and eliglustat is a P-gp inhibitor. [28610] [57803] Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [57803] [64608] Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with eliglustat. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); eliglustat is an inhibitor of P-gp. [57803] [60911] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with eliglustat. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); eliglustat is an inhibitor of P-gp. [57803] [60911] Solifenacin: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include solifenacin. [30515] [57803] Sorafenib: (Major) Avoid coadministration of sorafenib with eliglustat due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [31832] [57803] Sotalol: (Major) Concomitant use of sotalol and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28225] [28234] [57803] Spironolactone: (Major) Coadministration of eliglustat and spironolactone is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Spironolactone is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [62209] Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Coadministration of eliglustat and spironolactone is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Spironolactone is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [62209] St. John's Wort, Hypericum perforatum: (Major) Coadministration of eliglustat and St. John's Wort, Hypericum perforatum significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. St. John's Wort is a strong CYP3A inducer, and eliglustat is a CYP3A substrate. [57803] Stiripentol: (Moderate) Consider a dose adjustment of eliglustat when coadministered with stiripentol. Coadministration may alter plasma concentrations of eliglustat resulting in an increased risk of adverse reactions and/or decreased efficacy. Eliglustat is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. [57803] [63456] Streptogramins: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of dalfopristin; quinupristin and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Dalfopristin; quinupristin is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [28491] [57803] Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with eliglustat. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Sunitinib can prolong the QT interval. [31970] [57803] Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with eliglustat. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28611] [55401] [57803] [60497] Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with eliglustat is necessary. Talazoparib is a P-gp substrate and eliglustat is a P-gp inhibitor. [57803] [63651] Tamoxifen: (Major) Concomitant use of tamoxifen and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [57803] [61870] [61871] [61872] [63589] Tamsulosin: (Moderate) Coadministration of tamsulosin and eliglustat may result in increased concentrations of tamsulosin. Use tamsulosin with caution in patients receiving eliglustat, particularly if the tamsulosin dose is greater than 0.4 mg, and monitor closely for tamsulosin-related adverse effects including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 and CYP3A4 substrate; eliglustat is a CYP2D6 inhibitor. [29677] [57803] Telavancin: (Moderate) Due to increased risk of QT interval prolongation and torsade de pointes (TdP), use caution if telavancin is administered with eliglustat. Telavancin has been associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [36615] [57803] Telmisartan; Amlodipine: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of amlodipine and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Amlodipine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [29090] [57803] Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with eliglustat is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and eliglustat is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus. [50586] [57803] Tenofovir Alafenamide: (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [57803] [57923] [60269] [60614] [60688] Tenofovir Alafenamide: (Major) Coadministration of tenofovir alafenamide and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [57803] [57923] [60269] [60614] [60688] Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir, PMPA and eliglustat may result in increased concentrations of tenofovir. Monitor patients closely for tenofovir-related adverse effects including nausea, diarrhea, headache, asthenia, and nephrotoxicity. Tenofovir is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. For coadministration with P-gp substrates, eliglustat's product labeling recommends monitoring therapeutic drug concentrations of the P-gp substrate, if possible, or consideration of a dosage reduction and titrating to clinical effect. [28193] [57803] Terbinafine: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of terbinafine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both terbinafine and a strong or moderate CYP3A inhibitor is contraindicated. Terbinafine is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration with CYP2D6 inhibitors, such as terbinafine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Physiology-based pharmacokinetic (PBPK) models suggest that terbinafine may increase the Cmax and AUC of eliglustat 3.8- and 4.5-fold, respectively, in EMs and 1.6-fold (both Cmax and AUC) in IMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with terbinafine (moderate 2D6 inhibitor) and a moderate 3A4 inhibitor may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs. [57803] Tetrabenazine: (Major) Coadministration of tetrabenazine and eliglustat may result in increased concentrations of the primary metabolites of tetrabenazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of tetrabenazine. Although specific guidance is not available, FDA-approved labeling for tetrabenazine recommends a maximum of 25 mg/dose or 50 mg/day in patients taking a concurrent CYP2D6 inhibitor (e.g., quinidine, fluoxetine, paroxetine). Tetrabenazine is a CYP2D6 substrate associated with a small increase in the corrected QT interval (QTc). Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [34389] [57803] Tezacaftor; Ivacaftor: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ivacaftor and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Ivacaftor and its primary metabolite M1 are considered weak CYP3A inhibitors; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. [48524] [57803] Thioridazine: (Contraindicated) Coadministration of thioridazine and eliglustat is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and is contraindicated for use with other drugs that may prolong the QT interval, such as eliglustat. In addition, coadministration of thioridazine, a CYP2D6 substrate, and eliglustat, a CYP2D6 inhibitor, may result in elevated phenothiazine concentrations, further increasing the risk for serious adverse events (e.g., cardiac arrhythmias). [43069] [57803] Thiothixene: (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of thiothixene and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Thiothixene is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as thiothixene, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [46957] [57803] Ticagrelor: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ticagrelor and eliglustat is not recommended. Ticagrelor is a weak CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Reduce eliglustat dose to 84 mg PO once daily in extensive CYP2D6 metabolizers with hepatic impairment. Eliglustat exposure and the risk of serious adverse events may be increased. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. In addition, coadministration of eliglustat with ticagrelor, a P-gp substrate may result in increased concentrations of ticagrelor; monitor patients closely for adverse events, including signs and symptoms of bleeding. [44951] [57803] Timolol: (Moderate) Coadministration of timolol and eliglustat may result in increased plasma concentrations of timolol. Consider reducing the dosage of oral timolol and titrating to clinical effect. Timolol is a CYP2D6 substrate; eliglustat is a CYP2D6 inhibitor. [28540] [57803] Tipranavir: (Contraindicated) Coadministration of tipranavir and eliglustat is contraindicated. Tipranavir is a strong CYP2D6 and CYP3A inhibitor and P-glycoprotein (P-gp) substrate; its use is contraindicated with other drugs that are highly dependent on CYP3A for metabolic clearance. Eliglustat is a CYP2D6 and CYP3A substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of tipranavir and eliglustat may result in significantly increased plasma concentrations eliglustat, increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). In addition, the inhibition of P-gp transport caused by eliglustat may result in increased plasma concentration of tipranavir. [32130] [57803] Tolterodine: (Major) Coadministration of tolterodine and eliglustat may result in increased tolterodine concentrations and an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely for both cardiac and anticholinergic adverse effects. No empiric dosage adjustment is required for either drug. Tolterodine is CYP2D6 substrate associated with dose-dependent prolongation of the QT interval, especially in CYP2D6 poor metabolizers (PMs). Eliglustat is CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of tolterodine and eliglustat may result in additive effects on the QT interval and increased plasma concentrations of tolterodine, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [31112] [57803] Topotecan: (Major) Avoid coadministration of eliglustat with oral topotecan due to increased topotecan exposure; eliglustat may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and eliglustat is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone. [33536] [33578] [46322] [57803] Toremifene: (Major) Avoid coadministration of eliglustat with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28822] [57803] Tramadol: (Moderate) Coadministration of tramadol and eliglustat may result in a reduction in the metabolic conversion and clearance of tramadol, increasing the risk for serious adverse events including seizures and serotonin syndrome. In addition, coadministration of tramadol and eliglustat may result in decreased analgesia. If coadministration is necessary, monitor patients closely for tramadol-related adverse effects and diminished analgesic efficacy. The analgesic activity of tramadol is due to both the parent drug and the pharmacologically active metabolite M1. Because the metabolism of tramadol to M1 is dependent on CYP2D6 and eliglustat is an inhibitor of CYP2D6, therapeutic response may be affected. [28314] [57803] Tramadol; Acetaminophen: (Moderate) Coadministration of tramadol and eliglustat may result in a reduction in the metabolic conversion and clearance of tramadol, increasing the risk for serious adverse events including seizures and serotonin syndrome. In addition, coadministration of tramadol and eliglustat may result in decreased analgesia. If coadministration is necessary, monitor patients closely for tramadol-related adverse effects and diminished analgesic efficacy. The analgesic activity of tramadol is due to both the parent drug and the pharmacologically active metabolite M1. Because the metabolism of tramadol to M1 is dependent on CYP2D6 and eliglustat is an inhibitor of CYP2D6, therapeutic response may be affected. [28314] [57803] Trandolapril; Verapamil: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PM), coadministration of verapamil (including trandolapril; verapamil) and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both verapamil and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Verapamil is a moderate CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as verapamil, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. In addition, coadministration of eliglustat with P-gp substrates (e.g., verapamil) may result in increased concentrations of the concomitant drug; monitor patients closely for adverse events, and consider reducing the dosage of verapamil and titrating to clinical effect. [29702] [34695] [56565] [57803] Trazodone: (Major) Concomitant use of trazodone and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [38831] [57803] Triclabendazole: (Moderate) Concomitant use of triclabendazole and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [57803] [63962] Tricyclic antidepressants: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Trifluoperazine: (Minor) Coadministration of trifluoperazine and eliglustat may result in increased concentrations of the phenothiazine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Consider reducing the dosage of phenothiazine and titrating to clinical effect. Trifluoperazine is a CYP2D6 substrate associated with a possible risk for QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28415] [57803] Trimipramine: (Moderate) Coadminister tricyclic antidepressants (TCAs) and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and a TCA are used together, consider reducing the dosage of the TCA and titrating to clinical effect. When available, monitoring antidepressant serum concentrations may be beneficial. Eliglustat is a CYP2D6 inhibitor, and tricyclic antidepressants are CYP2D6 substrates. [28225] [28416] [57803] Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [45411] [57803] Trofinetide: (Major) Coadministration of eliglustat and trofinetide is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; trofinetide is a weak CYP3A inhibitor. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [68701] Tucatinib: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of tucatinib and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both tucatinib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Tucatinib is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors such as tucatinib increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [57803] [65295] Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with eliglustat. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; eliglustat is a P-gp inhibitor. [57803] [64874] Valproic Acid, Divalproex Sodium: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of valproic acid and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of valproic acid and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Valproic acid is a weak CYP3A4 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP3A4 inhibitors, such as valproic acid, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [44726] [57803] Vandetanib: (Major) Avoid coadministration of vandetanib with eliglustat due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [43901] [57803] Vardenafil: (Moderate) Concomitant use of vardenafil and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28216] [57803] Vemurafenib: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include vemurafenib. [45335] [57803] Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with eliglustat due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of eliglustat. Venetoclax is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study. [57803] [60706] Venlafaxine: (Major) Concomitant use of venlafaxine and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [33715] [57803] Verapamil: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PM), coadministration of verapamil (including trandolapril; verapamil) and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both verapamil and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Verapamil is a moderate CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as verapamil, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. In addition, coadministration of eliglustat with P-gp substrates (e.g., verapamil) may result in increased concentrations of the concomitant drug; monitor patients closely for adverse events, and consider reducing the dosage of verapamil and titrating to clinical effect. [29702] [34695] [56565] [57803] Viloxazine: (Major) Coadministration of eliglustat and viloxazine is not recommended in poor CYP2D6 metabolizers (PMs). In normal (extensive) CYP2D6 metabolizers with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Viloxazine is a weak CYP3A and weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [66575] Vincristine Liposomal: (Major) Eliglustat inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together. [28498] [34656] [51432] [57803] Vincristine: (Major) Eliglustat inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together. [28498] [34656] [51432] [57803] Voclosporin: (Moderate) Concomitant use of voclosporin and eliglustat may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [57803] [66336] Vonoprazan: (Major) Coadministration of eliglustat and vonoprazan is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; vonoprazan is a weak CYP3A inhibitor. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67585] Vonoprazan; Amoxicillin: (Major) Coadministration of eliglustat and vonoprazan is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; vonoprazan is a weak CYP3A inhibitor. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67585] Vonoprazan; Amoxicillin; Clarithromycin: (Major) Coadministration of eliglustat and vonoprazan is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; vonoprazan is a weak CYP3A inhibitor. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [57803] [67585] (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of clarithromycin and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both clarithromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and clarithromycin can independently prolong the QT interval, and coadministration increases this risk. Clarithromycin is a strong CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors such as clarithromycin increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. [25238] [28225] [57803] Voriconazole: (Major) Avoid coadministration of eliglustat with voriconanzole due to the risk of QT prolongation. Coadministration is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs), and when concomitantly used with a moderate or strong CYP2D6 inhibitor in all patients. Eliglustat is a CYP3A4 and CYP2D6 substrate that causes PR, QRS, and QT prolongation at elevated plasma concentrations; the risk is highest in CYP2D6 IMs and PMs because a larger portion of the dose is metabolized via CYP3A. Voriconazole is a strong CYP3A4 inhibitor that is also associated with QT prolongation. [28158] [57803] Vorinostat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include vorinostat. [32789] [57803] Voxelotor: (Major) Avoid coadministration of eliglustat with voxelotor in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Concurrent use is contraindicated in EMs and IMs also receiving a strong or moderate CYP2D6 inhibitor. Eliglustat is a CYP3A and CYP2D6 substrate. Voxelotor is a moderate inhibitor of CYP3A. Concurrent use may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). [57803] [64778] Zafirlukast: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of zafirlukast and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of zafirlukast and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Zafirlukast is a weak CYP3A4 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP3A4 inhibitors, such as zafirlukast, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). [28222] [57803] Ziprasidone: (Major) Concomitant use of ziprasidone and eliglustat should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [28233] [57803]
        Revision Date: 03/28/2024, 01:48:00 AM

        References

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        Monitoring Parameters

        • LFTs

        US Drug Names

        • CERDELGA
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