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Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe

Belmatoug, Nadia; Di Rocco, Maja; Fraga, Cristina; Giraldo, Pilar; Hughes, Derralynn; Lukina, Elena; Maison-Blanche, Pierre; Merkel, Martin; Niederau, Claus and Plöckinger, Ursula, et al. (2017) In European Journal of Internal Medicine 37. p.25-32
Abstract

Purpose: 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... (More)

Purpose: 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.

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keywords
Drug interactions, Drug metabolism, Eliglustat, Enzyme replacement/augmentation therapy, Substrate reduction therapy, Type 1 Gaucher disease
in
European Journal of Internal Medicine
volume
37
pages
25 - 32
publisher
Elsevier
external identifiers
  • scopus:84994285410
  • wos:000393967300030
ISSN
0953-6205
DOI
10.1016/j.ejim.2016.07.011
language
English
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yes
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9ae8ea8a-b30a-4b0c-889b-75442e326b9f
date added to LUP
2016-12-02 13:09:57
date last changed
2018-05-06 04:28:30
@article{9ae8ea8a-b30a-4b0c-889b-75442e326b9f,
  abstract     = {<p>Purpose: 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.</p>},
  author       = {Belmatoug, Nadia and Di Rocco, Maja and Fraga, Cristina and Giraldo, Pilar and Hughes, Derralynn and Lukina, Elena and Maison-Blanche, Pierre and Merkel, Martin and Niederau, Claus and Plöckinger, Ursula and Richter, Johan and Stulnig, Thomas M. and vom Dahl, Stephan and Cox, Timothy M.},
  issn         = {0953-6205},
  keyword      = {Drug interactions,Drug metabolism,Eliglustat,Enzyme replacement/augmentation therapy,Substrate reduction therapy,Type 1 Gaucher disease},
  language     = {eng},
  pages        = {25--32},
  publisher    = {Elsevier},
  series       = {European Journal of Internal Medicine},
  title        = {Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe},
  url          = {http://dx.doi.org/10.1016/j.ejim.2016.07.011},
  volume       = {37},
  year         = {2017},
}