A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease.
IBD
filgotinib
ozanimod
small molecule drugs
tofacitinib
upadacitinib
Journal
United European gastroenterology journal
ISSN: 2050-6414
Titre abrégé: United European Gastroenterol J
Pays: England
ID NLM: 101606807
Informations de publication
Date de publication:
26 Mar 2024
26 Mar 2024
Historique:
received:
24
10
2023
accepted:
21
01
2024
medline:
27
3
2024
pubmed:
27
3
2024
entrez:
27
3
2024
Statut:
aheadofprint
Résumé
Small molecule drugs are becoming increasingly used in the treatment of inflammatory bowel diseases (IBD). However, unlike monoclonal antibody drugs, which have few interactions with other medications, the pharmacokinetics of small molecule drugs are complex and may be influenced by a myriad of drug-drug interactions (DDI) as well as by patient characteristics and food intake. This review aims to provide a concise practical guide to small molecule drug interactions for the use of IBD physicians. It starts with a brief overview of the main metabolizing enzymes and transporters involved in drug interactions and the Food and Drug Administration's (FDA) approach to determining drug-interaction hazard thresholds. It is then followed by a more detailed review of the pharmacokinetics of four novel small molecules approved in IBD: Tofacitinib, Upadacitinib, Filgotinib, and Ozanimod, including their known interactions and specific warnings. This review will also inform readers on challenges in determining the actual magnitude of interactions and their clinical relevance, including the arbitrary nature of some hazard thresholds, the inference of the impact on metabolizing enzymes and transporters from single-drug assays which may not reflect poly-pharmaceutical regimens, and other challenges in this field which the IBD physician needs to be cognizant of. In practice, before administering a small molecule drug, it is advisable to evaluate any potential interactions with other medications the patient is receiving. An increased awareness by health care professionals and patients, may reduce the possible risks associated with DDI of small molecule IBD drugs.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.
Références
Taleban S, Colombel JF, Mohler MJ, Fain MJ. Inflammatory bowel disease and the elderly: a review. J Crohn's Colitis. 2015;9(6):507–515. https://doi.org/10.1093/ecco‐jcc/jjv059
Stallmach A, Hagel S, Gharbi A, Settmacher U, Hartmann M, Schmidt C, et al. Medical and surgical therapy of inflammatory bowel disease in the elderly—prospects and complications. J Crohn's Colitis. 2011;5(3):177–188. https://doi.org/10.1016/j.crohns.2011.02.001
Cross RK, Wilson KT, Binion DG. Polypharmacy and Crohn's disease. Aliment Pharmacol Therapeut. 2005;21(10):1211–1216. https://doi.org/10.1111/j.1365‐2036.2005.02429.x
Wang J, Nakamura TI, Tuskey AG, Behm BW. Polypharmacy is a risk factor for disease flare in adult patients with ulcerative colitis: a retrospective cohort study. Intestinal Res. 2019;17(4):496–503. https://doi.org/10.5217/ir.2019.00050
Sekhri S, Yarur AJ. Integrating new and emerging therapies into inflammatory bowel disease clinical practice. Curr Opin Gastroenterol. 2022;38(4):328–336. https://doi.org/10.1097/mog.0000000000000851
Gibaldi M, Boyes RN, Feldman S. Influence of first‐pass effect on availability of drugs on oral administration. J Pharmaceut Sci. 1971;60(9):1338–1340. https://doi.org/10.1002/jps.2600600909
Guengerich FP. CYTOCHROME P‐450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol. 1999;39:1–17. https://doi.org/10.1146/annurev.pharmtox.39.1.1
Eiselt R, Domanski T, Zibat A, Mueller R, Presecan‐Siedel E, Hustert E, et al. Identification and functional characterization of eight CYP3A4 protein variants. Pharmacogenetics. 2001;11(5):447–458. https://doi.org/10.1097/00008571‐200107000‐00008
Wolbold R, Klein K, Burk O, Nüssler AK, Neuhaus P, Eichelbaum M, et al. Sex is a major determinant of CYP3A4 expression in human liver. Hepatology. 2003;38(4):978–988. https://doi.org/10.1002/hep.1840380424
Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Pharmacokinet. 1997;33(2):103–121. https://doi.org/10.2165/00003088‐199733020‐00003
Aquilante CL, Niemi M, Gong L, Altman RB, Klein TE. PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 8. Pharmacogenet Genomics. 2013;23(12):721–728. https://doi.org/10.1097/fpc.0b013e3283653b27
Totah R, Rettie A. Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clin Pharmacol & Ther. 2005;77(5):341–352. https://doi.org/10.1016/j.clpt.2004.12.267
Speed WC, Kang SP, Tuck DP, Harris LN, Kidd KK. Global variation in CYP2C8–CYP2C9 functional haplotypes. Pharmacogenomics J. 2009;9(4):283–290. https://doi.org/10.1038/tpj.2009.10
Cabaleiro T, Román M, Ochoa D, Talegón M, Prieto‐Pérez R, Wojnicz A, et al. Evaluation of the relationship between sex, polymorphisms in CYP2C8 and CYP2C9, and pharmacokinetics of angiotensin receptor blockers. Drug Metabol Dispos. 2013;41(1):224–229. https://doi.org/10.1124/dmd.112.046292
Tzveova R, Naydenova G, Yaneva T, Dimitrov G, Vandeva S, Matrozova Y, et al. Gender‐specific effect of CYP2C8*3 on the risk of essential hypertension in Bulgarian patients. Biochem Genet. 2015;53(11‐12):319–333. https://doi.org/10.1007/s10528‐015‐9696‐7
Di L. The impact of carboxylesterases in drug metabolism and pharmacokinetics. Curr Drug Metabol. 2019;20(2):91–102. https://doi.org/10.2174/1389200219666180821094502
A Finch, Pillans P. P‐glycoprotein and its role in drug‐drug interactions. 2014:137–139.
DuBuske LM. The role of P‐glycoprotein and organic anion‐transporting polypeptides in drug interactions. Drug Saf. 2005;28(9):789–801. https://doi.org/10.2165/00002018‐200528090‐00004
Tirona RG, Kim RB. Pharmacogenomics of organic anion‐transporting polypeptides (OATP). Adv Drug Deliv Rev. 2002;54(10):1343–1352. https://doi.org/10.1016/s0169‐409x(02)00077‐7
Food & Drug Administration. Drug development and drug interactions | table of substrates, inhibitors and inducers; 2023.
Committee for Medicinal Products for Human U. EMA assessment report: Xeljanz; 2017.
Galapagos Biotech L. Zseleca 100 mg film‐coated tablets 2023.
Committee for Medicinal Products for Human U. EMA assessment report: Rinvoq; 2019.
RxAbbvie. Prescribing information: RINVOQ. 2019.
Committee for Medicinal Products for Human U. Assessment report: Jyseleca; 2020.
Bristol Myers S. Prescribing information: ZEPOSIA; 2020.
Sandborn WJ, Feagan BG, D’Haens G, Wolf DC, Jovanovic I, Hanauer SB, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385(14):1280–1291. https://doi.org/10.1056/nejmoa2033617
Food & Drug Administration. FDA requires warnings about increased risk of serious heart‐related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions; 2021.
Bethesda. LiverTox: clinical and research information on drug‐induced liver injury. National Institute of Diabetes and Digestive and Kidney Diseases 2012.
Burr NE, Gracie DJ, Black CJ, Ford AC. Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta‐analysis. Gut. 2022;71(10):1976–1987. https://doi.org/10.1136/gutjnl‐2021‐326390
Pfizer. Prescribing information: XELJANZ. 2012.
Vong C, Martin SW, Deng C, Xie R, Ito K, Su C, et al. Population pharmacokinetics of tofacitinib in patients with moderate to severe ulcerative colitis. Clin Pharmacol Drug Development. 2021;10(3):229–240. https://doi.org/10.1002/cpdd.899
Mohamed M.‐EF, Jungerwirth S, Asatryan A, Jiang P, Othman AA. Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high‐fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib. Br J Clin Pharmacol. 2017;83(10):2242–2248. https://doi.org/10.1111/bcp.13329
Trueman S, Mohamed MEF, Feng T, Lacerda AP, Marbury T, Othman AA. Characterization of the effect of hepatic impairment on upadacitinib pharmacokinetics. J Clin Pharmacol. 2019;59(9):1188–1194. https://doi.org/10.1002/jcph.1414
Namour F, Anderson K, Nelson C, Tasset C. Filgotinib: a clinical pharmacology review. Clin Pharmacokinet. 2022;61(6):819–832. https://doi.org/10.1007/s40262‐022‐01129‐y
Tran JQ, Hartung JP, Olson AD, Mendzelevski B, Timony GA, Boehm MF, et al. Cardiac safety of ozanimod, a novel sphingosine‐1‐phosphate receptor modulator: results of a thorough QT/QTc study. Clin Pharmacol Drug Development. 2018;7(3):263–276. https://doi.org/10.1002/cpdd.383
McGinley MP, Cohen JA. Sphingosine 1‐phosphate receptor modulators in multiple sclerosis and other conditions. Lancet. 2021;398(10306):1184–1194. https://doi.org/10.1016/s0140‐6736(21)00244‐0
Committee for Medicinal Products for Human U. EMA assessment report: Zeposia. European Medicines Agency; 2021.