title: A pooled analysis of adverse events in 393 adults with Gaucher disease type 1 from four clinical trials of oral eliglustat: Evaluation of frequency, timing, and duration.
abstract: Eliglustat, an oral substrate reduction therapy, is a first-line therapy for adults with Gaucher disease type 1 and a compatible CYP2D6 metabolizer phenotype. Clinicians have requested more information about frequency, timing, and duration of adverse events associated with eliglustat. Adverse event data as of January 31, 2013 for all patients who received at least one dose of eliglustat were pooled from four eliglustat clinical trials (393 patients representing 535 patient-years of exposure). The following 10 adverse events noted in the eliglustat US Prescribing Information (USPI) and EU Summary of Product Characteristics (SmPC) were evaluated with regard to frequency, drug-relatedness, severity, seriousness, duration, and timing of onset: headache, arthralgia, diarrhea, nausea, fatigue, flatulence, abdominal pain, upper abdominal pain, back pain, and extremity pain. Of 393 patients, 334 experienced one or more adverse events. Most patients (92%) continued taking eliglustat; 3% withdrew from a trial due to an adverse event. Among the 10 adverse events evaluated, none was reported as serious and none resulted in discontinuing treatment; most were mild or moderate, reported only once, and not considered eliglustat-related. The majority of adverse events noted in the eliglustat USPI and SmPC were non-serious, occasional, non-severe, and did not lead to drug discontinuation.
authors.affiliation: Sanofi Genzyme, 500 Kendall Street, Cambridge, MA 02142, USA. Electronic address: Judith.Peterschmitt@sanofi.com.
authors.forename: M Judith
authors.initials: MJ
authors.lastname: Peterschmitt
authors.affiliation: Sanofi Genzyme, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.affiliation: Sanofi Genzyme, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ibrahim
authors.affiliation: Prometrika, LLC, 100 CambridgePark Drive, Second Floor, Cambridge, MA 02140, USA.
authors.forename: James
authors.initials: J
authors.lastname: MacDougall
authors.affiliation: Sanofi Genzyme, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Underhill
authors.affiliation: Sanofi Genzyme, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Palni
authors.initials: P
authors.lastname: Patel
authors.affiliation: Sanofi Genzyme, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Sebastiaan J M
authors.initials: SJM
authors.lastname: Gaemers
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005776:Gaucher Disease / Q000188:drug therapy; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use; D011247:Pregnancy; D000293:Adolescent; D000368:Aged
chemical_list: C522917:eliglustat; D004791:Enzyme Inhibitors; D011759:Pyrrolidines
keywords: Acid β-glucosidase deficiency; Adverse events; Eliglustat; Gaucher disease type 1; Safety; Substrate reduction therapy