Gastrointestinal disturbances and their management in miglustat-treated patients
Tóm tắt
Miglustat (Zavesca®) is approved for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease (GD1) for whom enzyme replacement therapy is unsuitable, and for the treatment of progressive neurological manifestations in adult and paediatric patients with Niemann-Pick disease type C (NP-C). Gastrointestinal disturbances such as diarrhoea, flatulence and abdominal pain/discomfort have consistently been reported as the most frequent adverse events associated with miglustat during clinical trials and in real-world clinical practice settings. These adverse events are generally mild or moderate in severity, occurring mostly during the initial weeks of therapy. The mechanism underlying these gastrointestinal disturbances is the inhibition by miglustat of intestinal disaccharidase enzymes (mainly sucrase and maltase), leading to sub-optimal hydrolysis of carbohydrates and subsequent osmotic diarrhoea and altered colonic fermentation. Transient decreases in body weight, which are often observed during initial miglustat therapy, are considered likely due to gastrointestinal carbohydrate malabsorption and associated negative caloric balance. While most cases of diarrhoea resolve spontaneously during continued miglustat therapy, diarrhoea also responds well to anti-propulsive medications such as loperamide. Dietary modifications such as reduced consumption of dietary sucrose, maltose and lactose have been shown to improve the gastrointestinal tolerability of miglustat and reduce the magnitude of any changes in body weight, particularly if initiated at or before the start of therapy. Miglustat dose escalation at treatment initiation may also reduce gastrointestinal disturbances. This article discusses these aspects in detail, and provides practical recommendations on how to optimize the gastrointestinal tolerability of miglustat.
Tài liệu tham khảo
Actelion (2009) FDA advisory briefing book for miglustat (OGT 918, Zavesca®) in Niemann-Pick type C disease. Retrieved 11th April, 2011, from http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM196758.pdf.
Actelion (2010) Zavesca® (miglustat capsules) Prescribing Information. Available at: http://www.zavesca.com/pdfs/zavesca_pi.pdf. Accessed 9 June, 2011.
Andersson U, Butters TD, Dwek RA et al (2000) N-butyldeoxygalactonojirimycin: a more selective inhibitor of glycosphingolipid biosynthesis than N-butyldeoxynojirimycin, in vitro and in vivo. Biochem Pharmacol 59:821–829
Champion H, Ramaswami U, Imrie J, et al. (2010) Dietary modifications in patients receiving miglustat. J Inherit Metab Dis [Epub ahead of print]. doi:10.1007/s10545-008-0923-9.
Collins AJ, James PS, Smith MW (1989) Sugar-dependent selective induction of mouse jejunal disaccharidase activities. J Physiol 419:157–167
Cox T, Lachmann R, Hollak C et al. (2000) Novel oral treatment of Gaucher’s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 355:1481–1485
Dechelotte P (2004) Type 1 Gaucher’s disease in the adult. Nutritional management during initiation of treatment with miglustat. Presse Med 33:494–496
Elstein D, Hollak C, Aerts JM et al. (2004) Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease. J Inherit Metab Dis 27:757–766
Elstein D, Dweck A, Attias D et al. (2007) Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement. Blood 110:2296–2301
EMEA (2009) Miglustat (Zavesca®) summary of product characteristics. Retrieved 18 March, 2011, from http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000435/human_med_001171.jsp&murl=menus/medicines/medicines.jsp&mid=WC0b01ac058001d125.
Fischl MA, Resnick L, Coombs R et al. (1994) The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200–500 CD4 cells/mm3. J Acquir Immune Defic Syndr 7:139–147
Flores CA, Brannon PM, Bustamante SA et al. (1988) Effect of diet on intestinal and pancreatic enzyme activities in the pig. J Pediatr Gastroenterol Nutr 7:914–921
Giraldo P, Latre P, Alfonso P et al. (2006) Short-term effect of miglustat in every day clinical use in treatment-naive or previously treated patients with type 1 Gaucher’s disease. Haematologica 91:703–706
Giraldo P, Alfonso P, Atutxa K et al. (2009) Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project. Haematologica 94:1771–1775
Heitner R, Elstein D, Aerts J et al. (2002) Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease. Blood Cells Mol Dis 28:127–133
Hollak CE, Hughes D, van Schaik IN et al. (2009) Miglustat (Zavesca) in type 1 Gaucher disease: 5-year results of a post-authorisation safety surveillance programme. Pharmacoepidemiol Drug Saf 18:770–777
Lachmann RH, te Vruchte D, Lloyd-Evans E et al. (2004) Treatment with miglustat reverses the lipid-trafficking defect in Niemann-Pick disease type C. Neurobiol Dis 16:654–658
McCormack PL, Goa KL (2003) Miglustat. Drugs 63:2427–2434, discussion 2435–2426
Mehta A (2006) Clinical experience with substrate reduction therapy. Eur J Intern Med 17:S13–S15
Montalto M, Curigliano V, Santoro L et al. (2006) Management and treatment of lactose malabsorption. World J Gastroenterol 12:187–191
Ojetti V, Gigante G, Gabrielli M et al. (2010) The effect of oral supplementation with Lactobacillus reuteri or tilactase in lactose intolerant patients: randomized trial. Eur Rev Med Pharmacol Sci 14:163–170
Pastores GM, Weinreb NJ, Aerts H et al. (2004) Therapeutic goals in the treatment of Gaucher disease. Semin Hematol 41:4–14
Pastores GM, Barnett NL, Kolodny EH (2005) An open-label, noncomparative study of miglustat in type I Gaucher disease: efficacy and tolerability over 24 months of treatment. Clin Ther 27:1215–1227
Patterson MC, Vecchio D, Prady H et al. (2007) Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol 6:765–772
Patterson MC, Vecchio D, Jacklin E et al. (2010) Long-term miglustat therapy in children with Niemann-Pick disease type C. J Child Neurol 25:300–305
Pineda M, Wraith JE, Mengel E et al. (2009) Miglustat in patients with Niemann-Pick disease Type C (NP-C): a multicenter observational retrospective cohort study. Mol Genet Metab 98:243–249
Pineda M, Perez-Poyato MS, O’Callaghan M et al. (2010) Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series. Mol Genet Metab 99:358–366
Platt FM, Neises GR, Dwek RA et al. (1994) N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis. J Biol Chem 269:8362–8365
Pribila BA, Hertzler SR, Martin BR et al. (2000) Improved lactose digestion and intolerance among African-American adolescent girls fed a dairy-rich diet. J Am Diet Assoc 100:524–528
Rosensweig NS, Herman RH (1968) Control of jejunal sucrase and maltase activity by dietary sucrose or fructose in man. A model for the study of enzyme regulation in man. J Clin Invest 47:2253–2262
Schiffmann R, Fitzgibbon EJ, Harris C et al. (2008) Randomized, controlled trial of miglustat in Gaucher’s disease type 3. Ann Neurol 64:514–522
Shapiro BE, Pastores GM, Gianutsos J et al. (2009) Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment. Genet Med 11:425–433
Tierney M, Pottage J, Kessler H et al. (1995) The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases. J Acquir Immune Defic Syndr Hum Retrovirol 10:549–553
van Giersbergen PL, Dingemanse J (2007) Influence of food intake on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. J Clin Pharmacol 47:1277–1282
Welsh JD, Poley JR, Bhatia M et al. (1978) Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology 75:847–855
Wraith JE, Imrie J (2009) New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag 5:877–887
Wraith JE, Baumgartner MR, Bembi B et al. (2009) Recommendations on the diagnosis and management of Niemann-Pick disease type C. Mol Genet Metab 98:152–165
Wraith JE, Vecchio D, Jacklin E et al. (2010) Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long-term data from a clinical trial. Mol Genet Metab 99:351–357
Yang S,Tifft C (2006) Treat type I Gaucher disease with miglustat - experience with two patients. Lysosomal Disease Network WORLD symposium.
Zervas M, Somers KL, Thrall MA et al. (2001) Critical role for glycosphingolipids in Niemann-Pick disease type C. Curr Biol 11:1283–1287