Special features of the use of Zonisamide in the practise of an epileptologist: focus on safety
https://doi.org/10.56618/2071-2693_2024_16_2_101
EDN: LFWOFB
Abstract
INTRODUCTION. Currently, 23 AEDs with different mechanisms of action and different efficacy and safety/tolerability profiles are authorised in Russia. Clinical guidelines do not provide clear parameters for the choice of a particular drug in focal epilepsy – the decision on the AED regimen is at the discretion of the specialist. In such a situation, a comprehensive approach to AED selection is important, taking into account not only efficacy but also tolerability, especially in pharmacoresistant patients.
AIN. To evaluate the efficacy, tolerability and peculiarities of Zonisamide use in daily clinical practice in patients of different age groups.
MATERIALS AND METHODS. The study design was a review of the pharmacokinetic parameters of Zonisamide according to the literature and our own analysis of patient data in the structure of a retrospective observational cohort study. The study included patients with epilepsy receiving drug therapy with Zonisamide in 2 age groups: 1 gr. – adults up to 37 patients, 2 gr. – paediatrics (6 years – 17 years 11 months) – 13 patients. The age criterion in the paediatric group was chosen taking into account the authorised minimum age of administration of Zonisamide: 6 years and older.
RESULTS. The mean age in the cohort was 29.8±12.5 years. The male:female ratio was 1:1.2. The duration of disease in the cohort was 16.2±10.8 years (in group 1 = 19.7±10.1, in group 2 = 6.1±4.4). Zonisamide was used as monotherapy in 12 % and as polytherapy in 88 %. The average dosage in adults was – 301.6 mg/d. and in children – 182.7 mg/d. In the cohort, the combination of Zonisamide with levetiracitam dominated in polytherapy, followed by valproic acid and lacosamide in descending order.
A positive response to the therapy was observed in 36 (71 %) patients. Lack of efficacy or insufficient efficacy (less than 50 % reduction in seizure frequency) was observed in 14 (29 %) patients, but 40 % of them reported positive dynamics in the reduction of seizure severity and/or duration.
Adverse drug reactions were reported in 15 people. The average distribution of adverse drug reactions per person was 1.3.
Discontinuation of the drug due to intolerance occurred in 2(4 %) cases.
CONCLUSION. Zonisamide is used in a wide range of epilepsies: from idiopathic focal epilepsies to pharmacoresistant epilepsies in neurosurgical patients. Side effects of Zonisamide occur in less than one third of patients and are of mild to moderate severity.
Supporting agencies: The work was performed under the framework of the State assignment of the Ministry of Health of the Russian Federation (No. 056-00119-22-00 Topic ‘’Risk stratification, selection of optimal surgical treatment strategy and prediction of outcomes in patients with drug-resistant structural epilepsy’’). EGISU No 122011900530-8 (2022–2024) with the financial support of ‘’Firm EUROSERVICE’’.
About the Authors
N. E. Ivanova
Polenov Neurosurgery Institute – the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Natalia E. Ivanova – Dr. of Sci. (Med.), Full Professor, Distinguished Doctor of the Russian Federation, Corresponding Member of the Russian Academy of
Medical and Technical Sciences, Academician of the Academy of Medical and Technical Sciences, Full Member of the Petrovskaya Academy of Sciences and Arts, Member of the Board of the Association of Neurosurgeons of Russia, Member of the Board of the Babchin Association of Neurosurgeons, Member of the Geographical Society of Russia, Doctor of Functional and Ultrasound Diagnostics, Head at the Scientific Department of Russian Neurosurgical Institute, Head at the Scientific Department; Professor at the Department of Neurology and Psychiatry of the Institute of Medical Education
12 Mayakovskogo street, St. Petersburg, 191025
K. A. Samochernykh
Polenov Neurosurgery Institute – the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Konstantin A. Samochernykh – Dr. of Sci. (Med.), Professor of the Russian Academy of Sciences, Neurosurgeon of the Highest Category at the Department of Neurosurgery for Children No. 7, Director
12 Mayakovskogo street, St. Petersburg, 191025
N. O. Denigina
Polenov Neurosurgery Institute – the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Nina O. Denigina – Cand. of Sci. (Pedagogics), Associate Professor, Research Assistant at the Epilepsy Disorder Research Laboratory
12 Mayakovskogo street, St. Petersburg, 191025
D. Yu. Shalygin
Polenov Neurosurgery Institute – the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Dmitrii Yu. Shalygin – Neurologist, Postgraduate Student at the Department of Neurology with Clinic, Senior Laboratory Assistant at the Department of Neurology with Clinic
12 Mayakovskogo street, St. Petersburg, 191025
G. V. Odintsova
Polenov Neurosurgery Institute – the branch of Almazov National Medical Research Centre
Russian Federation
Russian Federation
Galina V. Odintsova – Cand. of Sci. (Med.), Senior Researcher, Head at the Epilepsy Disorder Research Laboratory
12 Mayakovskogo street, St. Petersburg, 191025
References
1. Romanov A. S., Sharakhova E. F. Marketing research on the national antiepileptic drug market in Russia. Journal of siberian medical sciences. 2022;6(4):48–60. (In Russ.)]. Doi: 10.31549/2542-11742022-6-4-48-60. EDN: PCIFNP.
2. Mula M., Zaccara G., Galimberti C. A. et al. Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drugresistant focal epilepsy. Epilepsia. 2019;60(6):1114–1123. Doi: 10.1111/epi.14685.
3. Nevitt S. J., Sudell M., Cividini S., Marson A. G., Tudur Smith C. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2022;4(4):CD011412. Doi: 10.1002/14651858.CD011412.pub4.
4. Kwan P., Arzimanoglou A., Berg A. T. et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies [published correction appears in Epilepsia. 2010 Sep;51(9):1922]. Epilepsia. 2010;51(6):1069–1077. Doi: 10.1111/j.1528-1167.2009.02397.x.
5. Odincova G. V., Abramov K. B., Ivanova N. E., Samochernyh K. A., Hachatryan V. A., Konradi A. O., Zabrodskaya Yu. M., Dengina N. O. “EPILEPSY 90-80-70”: the intersectoral global action plan on epilepsy and other neurological disorders (2022–2031). Translational Medicine. 2023;10(4):285–292. (In Russ.)]. Doi: 10.18705/2311-44952023-10-4-285-292. EDN: ADUZHV.
6. Reimers A., Ljung H. An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy. Expert Opin Pharmacother. 2019;20(8):909–915. Doi: 10.1080/14656566.2019.1595584.
7. Ayvazyan S. O., Akzhigitov R. G., Alferova V. V. Epilepsy and epileptic status in adults and children: Clinical Recommendations. Moscow: Ministry of Health of the Russian Federation; 2022. (In Russ.)]. EDN: NMDIKC .
8. Gidal B. E., Resnick T., Smith M. C., Wheless J. W. Zonegran (zonisamide): A Comprehensive, Updated Review for the Clinician. Neurol Clin Pract. 2024;14(1):e200210. Doi: 10.1212/CPJ.0000000000200210.
9. Reimers A., Ljung H. An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy. Expert Opin Pharmacother. 2019;20(8):909–915. Doi: 10.1080/14656566.2019.1595584.
10. Janković S. M. Evaluation of zonisamide for the treatment of focal epilepsy: a review of pharmacokinetics, clinical efficacy and adverse effects. Expert Opin Drug Metab Toxicol. 2020;16(3):169–177. Doi: 10.1080/17425255.2020.1736035.
11. Instructions for medical use of the medicinal product Zonegran. Available from: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=e2999c3e-4bbe-4696b4a7-88ba607f6032 [Accessed 22 May 2024].
12. Baulac M., Patten A., Giorgi L. Long-term safety and efficacy of zonisamide versus carbamazepine monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy: results of a phase III, randomized, double-blind study. Epilepsia. 2014;55(10):1534–1543. Doi: 10.1111/epi.12749.
13. Guerrini R., Rosati A.., Bradshaw K, Giorgi L. Adjunctive zonisamide therapy in the long-term treatment of children with partial epilepsy: results of an open-label extension study of a phase III, randomized, double-blind, placebo-controlled trial. Epilepsia. 2014;55(4):568–578. Doi: 10.1111/epi.12548.
14. Mikulić I., Likić R., Janković S. M. Cost-Effectiveness of Zonisamide Versus Levetiracetam in Newly Diagnosed Focal Onset Epilepsy in Serbia. Value Health Reg Issues. 2022;(27):49–57. Doi: 10.1016/j.vhri.2021.05.007.
15. Gidal B. E., Resnick T., Smith M. C., Wheless J. W. Zonisamide: A Comprehensive, Updated Review for the Clinician. Neurol Clin Pract. 2024;14(1):e200210. Doi: 10.1212/CPJ.0000000000200210.
16. Bannikova V. D., Samochernyh N. K., Odincova G. V. Features of combined epilepsy and covid-19. Russian neurosurgical journal named after professor A. L. Polenov. 2022;14(S1):170. (In Russ.)]. EDN: FFWGHX.
17. Shalygin D. Yu., Ivanova N. E., Odincova G. V. Frequency of comorbid pathology in neurosurgical patients with pharmacoresistant epilepsy. Russian neurosurgical journal named after professor A. L. Polenov. 2024;16(special issue):294. (In Russ.)].
Review
For citations:
Ivanova N.E., Samochernykh K.A., Denigina N.O., Shalygin D.Yu., Odintsova G.V. Special features of the use of Zonisamide in the practise of an epileptologist: focus on safety. Russian Neurosurgical Journal named after Professor A. L. Polenov. 2024;16(2):101-111. (In Russ.) https://doi.org/10.56618/2071-2693_2024_16_2_101. EDN: LFWOFB
Views:
77
Email this article 