title: Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe.
abstract: OBJECTIVE
  In Gaucher disease, diminished activity of the lysosomal enzyme, acid β-glucosidase, leads to accumulation of glucosylceramides and related substrates, primarily in the spleen, liver, and bone marrow. Eliglustat is an oral substrate reduction therapy approved in the European Union and the United States as a first-line treatment for adults with type 1 Gaucher disease who have compatible CYP2D6 metabolism phenotypes. A European Advisory Council of experts in Gaucher disease describes the characteristics of eliglustat that are distinct from enzyme augmentation therapy (the standard of care) and miglustat (the other approved substrate reduction therapy) and recommends investigations and monitoring for patients on eliglustat therapy within the context of current recommendations for Gaucher disease management.
  
  
  RESULTS
  Eliglustat is a selective, potent inhibitor of glucosylceramide synthase, the enzyme responsible for biosynthesis of glucosylceramides which accumulate in Gaucher disease. Extensive metabolism of eliglustat by CYP2D6, and, to a lesser extent, CYP3A of the cytochrome P450 pathway, necessitates careful consideration of the patient's CYP2D6 metaboliser status and use of concomitant medications which share metabolism by these pathways. Guidance on specific assessments and monitoring required for eliglustat therapy, including an algorithm to determine eligibility for eliglustat, are provided.
  
  
  CONCLUSIONS
  As a first-line therapy for type 1 Gaucher disease, eliglustat offers eligible patients a daily oral therapy alternative to biweekly infusions of enzyme therapy. Physicians will need to carefully assess individual Gaucher patients to determine their appropriateness for eliglustat therapy. The therapeutic response to eliglustat and use of concomitant medications will require long-term monitoring.
authors: Referral Center for Lysosomal Diseases, University Beaujon Hospital Paris Nord Val de Seine, Assistance-Publique Hôpitaux de Paris, Department of Internal Medicine, 100 Boulevard du Général Leclerc, 92110 Clichy, France. Electronic address: nadia.belmatoug@aphp.fr.
authors: Nadia
authors: N
authors: Belmatoug
authors: Unit of Rare Diseases, Department Pediatrics, Gaslini Institute, Largo Gaslini 3, 16147 Genoa, Italy. Electronic address: majadirocco@ospedale-gaslini.ge.it.
authors: Maja
authors: M
authors: Di Rocco
authors: Department of Haematology, HDES Hospital, Ponta Delgada, Av. D. Manuel I, PDL, Açores, Portugal. Electronic address: maria.cf.barros@azores.gov.pt.
authors: Cristina
authors: C
authors: Fraga
authors: Translational Research Unit, Instituto Investigación Sanitaria Aragon, CIBER Enfermedades Raras (CIBERER), Zaragoza, Spain. Electronic address: giraldocastellano@gmail.com.
authors: Pilar
authors: P
authors: Giraldo
authors: Royal Free London NHS Foundation Trust, University College London, Department of Haematology, Pond St., London NW1 2QG, United Kingdom.
authors: Derralynn
authors: D
authors: Hughes
authors: Department of Orphan Diseases, Hematology Research Center, 4 Novy Zykovsky Lane, 125167 Moscow, Russia. Electronic address: elenalukina02@gmail.com.
authors: Elena
authors: E
authors: Lukina
authors: Bichat University Hospital, Cardiology Unit, 46 Rue Henri Huchard, 75018 Paris, France. Electronic address: ipmb@wanadoo.fr.
authors: Pierre
authors: P
authors: Maison-Blanche
authors: Department of Internal Medicine, Asklepios Klinik St. Georg, Lohmühlenstr. 5, 20099 Hamburg, Germany. Electronic address: m.merkel@asklepios.com.
authors: Martin
authors: M
authors: Merkel
authors: Katholisches Klinikum Oberhausen GmbH, St. Josef Hospital, Department of Medicine, Academic Teaching Hospital, Universität Duisburg-Essen, Mülheimer Str. 83, 46045 Oberhausen, Germany. Electronic address: c.niederau@kk-ob.de.
authors: Claus
authors: C
authors: Niederau
authors: Interdisziplinares Stoffwechsel-Centrum: Diabetes, Endokrinologie und Stoffwechsel, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13352 Berlin, Germany. Electronic address: ursula.ploeckinger@charite.de.
authors: Ursula
authors: U
authors: Plӧckinger
authors: Department of Hematology and Vascular Diseases, Skåne University Hospital, 221 85 Lund, Sweden. Electronic address: johan.richter@med.lu.se.
authors: Johan
authors: J
authors: Richter
authors: Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: thomas.stulnig@meduniwien.ac.at.
authors: Thomas M
authors: TM
authors: Stulnig
authors: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, University of Duesseldorf, Moorenstrasse 5, D-40225, Germany. Electronic address: Stephan.vomdahl@med.uni-duesseldorf.de.
authors: Stephan
authors: S
authors: Vom Dahl
authors: Department of Medicine, University of Cambridge, Box 157, Level 5, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom. Electronic address: tmc12@medschl.cam.ac.uk.
authors: Timothy M
authors: TM
authors: Cox
mesh_terms: D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D056947:Enzyme Replacement Therapy; D005060:Europe; D005776:Gaucher Disease / Q000188:drug therapy*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D010641:Phenotype; D017410:Practice Guidelines as Topic; D011759:Pyrrolidines / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; C522917:eliglustat; D019389:Cytochrome P-450 CYP2D6; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase
keywords: Drug interactions; Drug metabolism; Eliglustat; Enzyme replacement/augmentation therapy; Substrate reduction therapy; Type 1 Gaucher disease