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Skryabin V.Yu.

Moscow Research and Practical Centre of Addictions

Zastrozhin M.S.

Moscow Research Practical Narcology Center;
Russian Medical Academy for Continuous Professional Education;
University of California, San Francisco

Bryun E.A.

Moscow Research Practical Narcology Center;
Russian Medical Academy for Continuous Professional Education

Sychev D.A.

Russian Medical Academy of Continuous Professional Education

Pharmacogenetics of carbamazepine adverse drug reactions

Authors:

Skryabin V.Yu., Zastrozhin M.S., Bryun E.A., Sychev D.A.

More about the authors

Journal: Russian Journal of Pain. 2022;20(4): 70‑74

DOI: 10.17116/pain20222004170

Views: 6666

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To cite this article:

Skryabin VYu, Zastrozhin MS, Bryun EA, Sychev DA. Pharmacogenetics of carbamazepine adverse drug reactions. Russian Journal of Pain. 2022;20(4):70‑74. (In Russ.)
https://doi.org/10.17116/pain20222004170

Подписка 2025 (Russian Journal of Pain)
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Carbamazepine is widely used for epilepsy, trigeminal neuralgia and psychiatric disorders. However, therapy is often ineffective, and some patients experience adverse drug reactions (ADRs). This review systematized and presented up-to-date information on the studies devoted to pharmacogenetics of carbamazepine-associated ADRs. The authors analyze individual variants of genes encoding enzymes and transport proteins (mainly for dose-dependent ADRs) and HLA-system genes for idiosyncratic ADRs. Knowledge of pharmacogenetics of carbamazepine will allow development of approaches to personalized selection of effective and safe dose of therapy based on individual clinical and biological parameters.

Keywords:

neuropathic pain
trigeminal neuralgia
treatment
pharmacogenetics
adverse drug reactions
carbamazepine

Authors:

Skryabin V.Yu.

Moscow Research and Practical Centre of Addictions

Zastrozhin M.S.

Moscow Research Practical Narcology Center;
Russian Medical Academy for Continuous Professional Education;
University of California, San Francisco

Bryun E.A.

Moscow Research Practical Narcology Center;
Russian Medical Academy for Continuous Professional Education

Sychev D.A.

Russian Medical Academy of Continuous Professional Education

Received:

25.05.2022

Accepted:

23.09.2022

List of references:

  1. Davison SN. Clinical Pharmacology Considerations in Pain Management in Patients with Advanced Kidney Failure. Clin J Am Soc Nephrol. 2019;14(6):917-931.  https://doi.org/10.2215/CJN.05180418
  2. Davydov OS. Antiepileptic drugs: over than epilepsy (anticonvulsants drugs use in different pain syndromes). S.S. Korsakov Journal of Neurology and Psychiatry. 2013;113(4-2):58-65. (In Russ.).
  3. Dib-Hajj SD, Waxman SG. Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics. Annu Rev Neurosci. 2019;42:87-106.  https://doi.org/10.1146/annurev-neuro-070918-050144
  4. Maarbjerg S, Di Stefano G, Bendtsen L, Cruccu G. Trigeminal neuralgia — diagnosis and treatment. Cephalalgia. 2017;37(7):648-657.  https://doi.org/10.1177/0333102416687280
  5. Savust’yanenko AV. Carbamazepine use for neuropathic pain treatment: review of studies. Mezhdunarodnyj nevrologicheskij zhurnal. 2011;2(40):107-115. (In Russ.).
  6. Yip VLM, Pertinez H, Meng X, Maggs JL, Carr DF, Park BK, Marson AG, Pirmohamed M. Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine. Br J Clin Pharmacol. 2021;87(6):2572-2588. https://doi.org/10.1111/bcp.14667
  7. Iannaccone T, Sellitto C, Manzo V, Colucci F, Giudice V, Stefanelli B, Iuliano A, Corrivetti G, Filippelli A. Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters. Pharmaceuticals (Basel). 2021;14(3):204.  https://doi.org/10.3390/ph14030204
  8. Nechaev MO, Sychev DA, Zastrozhin MS, Grishina EA, Sorokin AS, Romanov AS, Aguzarov AD, Savchenko LM, Bryun EA. Pharmacogenetic aspects of efficacy and safety profile of carbamazepine (review). Narkologiya. 2019;18(4):68-82. (In Russ.).
  9. Karlov VA, Vlasov PN, Kozhokaru AB, Orlova AS. The efficacy and tolerability of extended release carbamazepine in adult patients with new-onset epilepsy using epileptiform activity index. S.S. Korsakov Journal of Neurology and Psychiatry. 2021;121(3):31-38. (In Russ.).
  10. Araya EI, Claudino RF, Piovesan EJ, Chichorro JG. Trigeminal Neuralgia: Basic and Clinical Aspects. Curr Neuropharmacol. 2020;18(2):109-119.  https://doi.org/10.2174/1570159X17666191010094350
  11. Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, Cramp C, Cockerell OC, Cooper PN, Doughty J, Eaton B, Gamble C, Goulding PJ, Howell SJ, Hughes A, Jackson M, Jacoby A, Kellett M, Lawson GR, Leach JP, Nicolaides P, Roberts R, Shackley P, Shen J, Smith DF, Smith PE, Smith CT, Vanoli A, Williamson PR; SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: An unblinded randomised controlled trial. Lancet. 2007;369(9566):1000-1015. https://doi.org/10.1016/S0140-6736(07)60460-7
  12. Jaramillo NM, Galindo IF, Vázquez AO, Cook HJ, LLerena A, López ML. Pharmacogenetic potential biomarkers for carbamazepine adverse drug reactions and clinical response. Drug Metabol Drug Interact. 2014;29(2):67-79.  https://doi.org/10.1515/dmdi-2013-0046
  13. Fricke-Galindo I, LLerena A, Jung-Cook H, López-López M. Carbamazepine adverse drug reactions. Expert Rev Clin Pharmacol. 2018;11(7):705-718.  https://doi.org/10.1080/17512433.2018.1486707
  14. Daly AK. Pharmacogenomics of adverse drug reactions. Genome Med. 2013;5(1):5.  https://doi.org/10.1186/gm409
  15. Khor AH-P, Lim K-S, Tan C-T, Wong S-M, Ng C-C. HLA-B*15:02 association with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in an Indian population: A pooled-data analysis and meta-analysis. Epilepsia. 2014;55(11):120-124.  https://doi.org/10.1111/epi.12802
  16. Błaszczyk B, Lasoń W, Czuczwar SJ. Antiepileptic drugs and adverse skin reactions: An update. Pharmacol Rep. 2015;67(3):426-434.  https://doi.org/10.1016/j.pharep.2014.11.009
  17. Chung W-H, Hung S-I, Hong H-S, Hsih M-S, Yang L-C, Ho H-C, Wu J-Y, Chen Y-T. Medical genetics: A marker for Stevens-Johnson syndrome. Nature. 2004;428(6982):486.  https://doi.org/10.1038/428486a
  18. Leckband SG, Kelsoe JR, Dunnenberger HM, George AL Jr, Tran E, Berger R, Müller DJ, Whirl-Carrillo M, Caudle KE, Pirmohamed M; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther. 2013;94(3):324-328.  https://doi.org/10.1038/clpt.2013.103
  19. Aihara M. Pharmacogenetics of cutaneous adverse drug reactions. J Dermatol. 2011;38(3):246-254.  https://doi.org/10.1111/j.1346-8138.2010.01196.x
  20. McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiūtė D, Carrington M, Sills GJ, Marson T, Jia X, de Bakker PI, Chinthapalli K, Molokhia M, Johnson MR, O’Connor GD, Chaila E, Alhusaini S, Shianna KV, Radtke RA, Heinzen EL, Walley N, Pandolfo M, Pichler W, Park BK, Depondt C, Sisodiya SM, Goldstein DB, Deloukas P, Delanty N, Cavalleri GL, Pirmohamed M. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364(12):1134-1143. https://doi.org/10.1056/NEJMoa1013297
  21. Bloch KM, Sills GJ, Pirmohamed M, Alfirevic A. Pharmacogenetics of antiepileptic drug-induced hypersensitivity. Pharmacogenomics. 2014;15(6):857-868.  https://doi.org/10.2217/pgs.14.65
  22. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, Furuya H, Takahashi Y, Muramatsu M, Kinoshita S, Abe M, Ikeda H, Kashiwagi M, Song Y, Ueta M, Sotozono C, Ikezawa Z, Hasegawa R; JSAR research group. HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Epilepsia. 2010;51(12):2461-2465. https://doi.org/10.1111/j.1528-1167.2010.02766.x
  23. Dong D, Sung C, Finkelstein EA. Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology. 2012;79(12):1259-1267. https://doi.org/10.1212/WNL.0b013e31826aac73
  24. Plumpton CO, Yip VLM, Alfirevic A, Marson AG, Pirmohamed M, Hughes DA. Cost-effectiveness of screening for HLA-A*31:01 prior to initiation of carbamazepine in epilepsy. Epilepsia. 2015;56(4):556-563.  https://doi.org/10.1111/epi.12937
  25. Pirmohamed M, Lin K, Chadwick D, Park BK. TNFα promoter region gene polymorphisms in carbamazepine-hypersensitive patients. Neurology. 2001;56(7):890-896.  https://doi.org/10.1212/wnl.56.7.890
  26. Alfirevic A, Mills T, Harrington P, Pinel T, Sherwood J, Jawaid A, Smith JC, March RE, Barratt BJ, Chadwick DW, Park BK, Pirmohamed M. Serious carbamazepine-induced hypersensitivity reactions associated with the HSP70 gene cluster. Pharmacogenet Genomics. 2006;16(4):287-296.  https://doi.org/10.1097/01.fpc.0000189800.88596.7a
  27. Thorn CF, Leckband SG, Kelsoe J, Leeder JS, Müller DJ, Klein TE, Altman RB. PharmGKB summary: carbamazepine pathway. Pharmacogenet Genomics. 2011;21(12):906-910.  https://doi.org/10.1097/FPC.0b013e328348c6f2
  28. Hayes JD, Flanagan JU, Jowsey IR. Glutathione Transferases. Annu Rev Pharmacol Toxicol. 2005;45:51-88.  https://doi.org/10.1146/annurev.pharmtox.45.120403.095857
  29. Zhao Y, Deng X, Song G, Qin S, Liu Z. The GSTM1 null genotype increased risk of gastric cancer: A meta-analysis based on 46 studies. PLoS One. 2013;8(11):e81403. https://doi.org/10.1371/journal.pone.0081403
  30. Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, Autrup JL, Baranova H, Bathum L, Benhamou S, Boffetta P, Bouchardy C, Breskvar K, Brockmoller J, Cascorbi I, Clapper ML, Coutelle C, Daly A, Dell’Omo M, Dolzan V, Dresler CM, Fryer A, Haugen A, Hein DW, Hildesheim A, Hirvonen A, Hsieh LL, Ingelman-Sundberg M, Kalina I, Kang D, Kihara M, Kiyohara C, Kremers P, Lazarus P, Marchand LL, Lechner MC, van Lieshout EM, London S, Manni JJ, Maugard CM, Morita S, Nazar-Stewart V, Noda K, Oda Y, Parl FF, Pastorelli R, Persson I, Peters WH, Rannug A, Rebbeck T, Risch A, Roelandt L, Romkes M, Ryberg D, Salagovic J, Schoket B, Seidegard J, Shields PG, Sim E, Sinnet D, Strange RC, Stucker I, Sugimura H, To-Figueras J, Vineis P, Yu MC, Taioli E. Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev. 2001;10(12):1239-1248.
  31. Kalapos MP. Carbamazepine-provoked hepatotoxicity and possible aetiopathological role of glutathione in the events. Retrospective review of old data and call for new investigation. Adverse Drug React Toxicol Rev. 2002;21(3):123-141.  https://doi.org/10.1007/BF03256188
  32. Ueda K, Ishitsu T, Seo T, Ueda N, Murata T, Hori M, Nakagawa K. Glutathione S-transferase M1 null genotype as a risk factor for carbamazepine-induced mild hepatotoxicity. Pharmacogenomics. 2007;8(5):435-442.  https://doi.org/10.2217/14622416.8.5.435
  33. He X-J, Jian L-Y, He X-L, Tang M, Wu Y, Xu Y-Y, Sun X-J, Zhao L-M. Association of ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms with the risk of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Chinese Han patients with epilepsy. Epilepsia. 2014;55(8):1301-1306. https://doi.org/10.1111/epi.12655
  34. Hung C-C, Chang W-L, Ho J-L, Tai J-J, Hsieh T-J, Huang H-C, Hsieh Y-W, Liou H-H. Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization. Pharmacogenomics. 2012;13(2):159-169.  https://doi.org/10.2217/pgs.11.141
  35. Puranik YG, Birnbaum AK, Marino SE, Ahmed G, Cloyd JC, Remmel RP, Leppik IE, Lamba JK. Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy. Pharmacogenomics. 2013;14(1):35-45.  https://doi.org/10.2217/pgs.12.180
  36. Dallas S, Miller DS, Bendayan R. Multidrug resistance-associated proteins: expression and function in the central nervous system. Pharmacol Rev. 2006;58(2):140-161.  https://doi.org/10.1124/pr.58.2.3
  37. Ma C-L, Wu X-Y, Zheng J, Wu Z-Y, Hong Z, Zhong M-K. Association of SCN1A, SCN2A and ABCC2 gene polymorphisms with the response to antiepileptic drugs in Chinese Han patients with epilepsy. Pharmacogenomics. 2014;15(10):1323-1336. https://doi.org/10.2217/pgs.14.89
  38. Kim W-J, Lee JH, Yi J, Cho Y-J, Heo K, Lee SH, Kim SW, Kim M-K, Kim KH, Lee BI, Lee MG. A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy. Pharmacogenet Genomics. 2010;20(4):249-256.  https://doi.org/10.1097/FPC.0b013e328338073a
  39. Chbili C, Fathallah N, Laouani A, Nouira M, Hassine A, Amor SB, Ammou SB, Salem CB, Saguem S. Effects of EPHX1 and CYP3A4*22 genetic polymorphisms on carbamazepine metabolism and drug response among Tunisian epileptic patients. J Neurogenet. 2016;30(1):16-21.  https://doi.org/10.3109/01677063.2016.1155571
  40. Saiz-Rodríguez M, Almenara S, Navares-Gómez M, Ochoa D, Román M, Zubiaur P, Koller D, Santos M, Mejía G, Borobia AM, Rodríguez-Antona C, Abad-Santos F. Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates. Biomedicines. 2020;8(4):94.  https://doi.org/10.3390/biomedicines8040094
  41. Park P-W, Seo YH, Ahn JY, Kim K-A, Park J-Y. Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients. J Clin Pharm Ther. 2009;34(5):569-574.  https://doi.org/10.1111/j.1365-2710.2009.01057.x
  42. Ganesapandian M, Ramasamy K, Adithan S, Narayan SK. Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on dose-adjusted plasma levels of carbamazepine in epileptic patients in South Indian population. Indian J Pharmacol. 2019;51(6):384-388.  https://doi.org/10.4103/ijp.IJP_122_19
  43. Al-Gahtany M, Karunakaran G, Munisamy M. Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity. BMC Genomics. 2014;15:2.  https://doi.org/10.1186/1471-2164-15-S2-P2
  44. Milovanovic DD, Radosavljevic I, Radovanovic M, Milovanovic JR, Obradovic S, Jankovic S, Milovanovic D, Djordjevic N. CYP3A5 polymorphism in Serbian paediatric epileptic patients on carbamazepine treatment. Ser J Exp Clin Res. 2015;16:93-99. 
  45. Pham TH, Huynh HTM, Vo HT, Tran HM. Effect of CYP3A5 genotypes on serum carbamazepine concentrations at steady-state in Vietnamese epileptic patients. Res J Pharm Technol. 2020;13:2802.

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