Information about Eliglustat
Eliglustat is an oral inhibitor of glucosylceramide synthase which is used in the therapy of type 1 Gaucher disease. Clinical experience with eliglustat is limited, but it not been linked to serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.
Mechanism of action of Eliglustat
Eliglustat (el" i gloo' stat) is a small molecule inhibitor of glucosylceramide synthase, the first and rate controlling step in the pathway of glycolipid synthesis. By inhibiting the pathway, lower levels of gylcolipid substrates are available, so that less of the substrate is available for lysosomal degradation and less glycosylceramide accumulates. Eliglustat was shown to decrease the intracellular accumulation of glycosylceramide in animal models of Gaucher disease. In several randomized controlled trials, eliglustat was shown to decrease spleen and liver volume and increase hemoglobin and platelet counts in patients with type 1 Gaucher disease. Eliglustat was also able to maintain clinical benefit in patients who had been maintained on long term enzyme replacement therapy with glucocerebrosidase infusions (the lysosomal enzyme that is deficient in type 1 Gaucher disease).
FDA approval information for Eliglustat
Eliglustat was approved as oral therapy of type 1 Gaucher Disease in the United States in 2015. Eliglustat is metabolized by the microsomal enzyme CYP 2D6 and serum levels are markedly affected by different CYP 2D6 isoenyzmes, so that it is recommended only for patients who are extensive, intermediate or poor metabolizers of CYP 2D6 and not for ultra-rapid metabolizers or patients who have an indeterminant or unknown metabolizer status.
Dosage and administration for Eliglustat
Eliglustat is available in tablets of 84 mg and the usual dose is 84 mg twice daily, but major dose adjustments are recommended for patients taking inhibitors of CYP 3A or 2D6.
Side effects of Eliglustat
Side effects can include fatigue, headache, nausea, diarrhea, back pain and muscle aches.
genetic disorder agents
- gaucher disease agents
glucosylceramide synthase inhibitors (substrate restriction therapy)
lysosomal acid lipase deficiency agents
- agalsidase beta, alglucosidase alfa, alpha1-proteinase inhibitor, elosulfase alfa, galsulfase, idursulfase, laronidase, pegademase
Huntington disease agents
Urea Cycle Disorder Agents