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Licensed Unlicensed Requires Authentication Published by De Gruyter May 30, 2019

Regulatory sciences and translational pharmacogenetics: amitriptyline as a case in point

  • Luana Mifsud Buhagiar EMAIL logo , Benjamin Micallef , John Joseph Borg , Helen Vella , Anthony Serracino Inglott and Godfrey LaFerla


Regulatory developments and clinical implementation, or the lack thereof, are primary clinchers, in the enduring endeavors to realize the translational quality of pharmacogenetics. Here, we present the case of amitriptyline, an established drug with pharmacogenetic implications. The integration of pharmacogenetic information in the official product literature and throughout the evaluation of safety concerns is considered. In our opinion, apart from emboldening genomic research in drug development and the valid pursuit towards global harmonization in the field, it is rational to look into the applicability of the data we have today.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Research funded by the ENDEAVOUR Scholarships scheme.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


[1] International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 2004;431:931–45.10.1038/nature03001Search in Google Scholar PubMed

[2] Prasad K, Breckenridge A. Pharmacogenomics: a new clinical or regulatory paradigm? European experiences of pharmacogenomics in drug regulation and regulatory initiatives. Drug Discov Today 2011;16:867–72.10.1016/j.drudis.2011.08.016Search in Google Scholar PubMed

[3] Maliepaard M, Nofziger C, Papaluca M, Zineh I, Uyama Y, Prasad K, et al. Pharmacogenetics in the evaluation of new drugs: a multiregional regulatory perspective. Nat Rev Drug Discov 2013;12:103–15.10.1038/nrd3931Search in Google Scholar PubMed

[4] Ehmann F, Caneva L, Prasad K, Paulmichl M, Maliepaard M, Llerena A, et al. Pharmacogenomic information in drug labels: Eur Med Agency perspective. Pharmacogenomics J 2015;15:201–10.10.1038/tpj.2014.86Search in Google Scholar

[5] Harper AR, Topol EJ. Pharmacogenomics in clinical practice and drug development. Nat Biotechnol 2012;30:1117–24.10.1038/nbt.2424Search in Google Scholar PubMed

[6] Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018;391:1357–66.10.1016/S0140-6736(17)32802-7Search in Google Scholar PubMed

[7] De Grandis G, Halgunset V. Conceptual and terminological confusion around personalised medicine: a coping strategy. BMC Med Ethics 2016;17:43.10.1186/s12910-016-0122-4Search in Google Scholar PubMed PubMed Central

[8] Sadée W, Dai Z. Pharmacogenetics/genomics and personalized medicine. Hum Mol Genet 2005;14:207–14.10.1093/hmg/ddi261Search in Google Scholar PubMed

[9] Dove ES, Özdemir V. All the post-genomic world is a stage: the actors and narrators required for translating pharmacogenomics into public health. Per Med 2013;10:213–6.10.2217/pme.13.10Search in Google Scholar PubMed PubMed Central

[10] Cheung KC, Nijenhuis M, Crommentuijn – van Rhenen M, Holsappel I. Evidence-based pharmacogenetic guidelines in the Netherlands. Presentation at the 2017 FIP Congress; May 2017; Stockholm (Sweden).Search in Google Scholar

[11] Nassan M, Nicholson WT, Elliott MA, Rohrer Vitek CR, Black JL, Frye MA, et al. Pharmacokinetic pharmacogenetic prescribing guidelines for antidepressants: a template for psychiatric precision medicine. Mayo Clin Proc 2016;91:897–907.10.1016/j.mayocp.2016.02.023Search in Google Scholar PubMed

[12] Borg JJ, Tanti A, Kouvelas D, Lungu C, Pirozynski M, Serracino-Inglott A, Aislaitner G. European Union pharmacovigilance capabilities: potential for the new legislation. Ther Adv Drug Saf 2015;6:120–40.10.1177/2042098615591802Search in Google Scholar PubMed PubMed Central

[13] European Medicines Agency. Guideline on key aspects for the use of pharmacogenomics in the pharmacovigilance of medicinalproducts. EMA/CHMP/281371/2013.EMA; 2015.Search in Google Scholar

[14] Swen JJ, Nijenhuis M, van Rhenen M, de Boer-Veger NJ, Buunk AM, Houwink EJ. Pharmacogenetic information in clinical guidelines: the European perspective. Clin Pharmacol Ther 2018;103:795–801.10.1002/cpt.1049Search in Google Scholar PubMed

[15] Bank PC, Caudle KE, Swen JJ, Gammal RS, Whirl-Carrillo M, Klein TE, et al. Comparison of the guidelines of the clinical pharmacogenetics implementation consortium and the dutch pharmacogenetics working group. Clin Pharmacol Ther 2018;103:599–618.10.1002/cpt.762Search in Google Scholar PubMed PubMed Central

[16] Reis-Pardal J, Rodrigues A, Rodrigues E, Fernandez-Llimos F. Comparing cytochrome P450 pharmacogenetic information available on United States drug labels and European Union Summaries of Product Characteristics. Pharmacogenomics J 2017;17:488–93.10.1038/tpj.2016.40Search in Google Scholar PubMed

[17] Shimazawa R, Ikeda M. Differences in pharmacogenomic biomarker information in package inserts from the United States, the United Kingdom and Japan. J Clin Pharm Ther 2013;38:468–75.10.1111/jcpt.12089Search in Google Scholar PubMed

[18] U.S. National Library of Medicine. FDA Label: amitriptyline hydrochrolide. DailyMed; NIH NLM.Search in Google Scholar

[19] Hicks JK, Swen JJ, Thorn CF, Sangkuhl K, Kharasch ED, Ellingrod VL, et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclicantidepressants. Clin Pharmacol Ther 2013;93:402–8.10.1038/clpt.2013.2Search in Google Scholar PubMed PubMed Central

[20] European Medicines Agency. Assessment report Referral under Article 30 of Directive 2001/83/EC. Committee for Medicinal Products for Human Use (CHMP); EMA/255467/2017. EMA; 2017.Search in Google Scholar

[21] European Commission. Commission Implementing Decision of 8.5.2017 concerning, in the framework of Article 30 of Directive 2001/83/EC of the European Parliament and of the Council, the marketing authorisations for “Saroten and associated names,” medicinal products for human use which contain the active substance “amitriptyline;” Brussels.Search in Google Scholar

[22] European Medicines Agency. List of nationally authorised medicinal products active substance: amitriptyline Procedure no.: PSUSA/00000168/201501.EMA/792231/2015.EMA; 2015.Search in Google Scholar

Received: 2019-02-03
Accepted: 2019-02-11
Published Online: 2019-05-30

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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