A randomized controlled trial to evaluate genotyping and therapeutic drug monitoring vs. only therapeutic drug monitoring as a strategy for risk minimization in epileptic patients on carbamazepine therapy

Year 2025, Volume: 3 Issue: 1, 27 - 35, 30.04.2025

Mahesh Belhekar , Vinayak A , Swati More , Sanchita Ambre , Hina Khimsuriya

https://doi.org/10.62425/rtpharma.1614127

Abstract

Objective: Carbamazepine (CBZ) is a widely prescribed antiepileptic drug for the treatment of focal seizures. CBZ gets metabolized by cytochrome enzymes mainly CYP3A5. It is difficult to predict clinically whether a patient is likely to suffer from CBZ toxicity. Hence, we planned to evaluate the use of genotyping and therapeutic drug monitoring (TDM) vs. only TDM in epileptic patients on CBZ as a strategy for risk minimization.

Methods: This double-blind, randomized controlled trial included 60 epileptic patients taking carbamazepine, divided into two equal groups. One group’s carbamazepine dosing was guided by genotyping, while the other group’s doses were based solely on clinical judgment.

Results: A total of 60 patients were enrolled in the study, in two arms, group A (genotyping and TDM both) and Group B (only TDM), each arm comprising 30 patients. Among the CYP3A5 metabolizer group, the frequency of expressors and non-expressors was (57%) and (43%), respectively. During follow-up visits, at one month, three cases of adverse drug reactions (ADRs) were reported. ADR count decreased to two cases during the three-month follow-up and further reduced to only one case of ADR at the 12-month assessment. It was found that there is no statistically significant association between CYP3A5 metabolizer and ADR occurrence.

Conclusion: Adding genotyping to TDM did not significantly reduce the risk of carbamazepine toxicity. However, genotyping may still be useful for patients who exhibit symptoms of toxicity.

Keywords

Carbamazepine , Drug Monitoring , Drug-Related Side Effects and Adverse Reactions , Genetic polymorphism , Risk Evaluation and Mitigation

Ethical Statement

1. I have read or have had read to me the information given in the Informed Consent Document for this study entitled “Evaluation of genotyping and therapeutic drug monitoring vs. only therapeutic drug monitoring as a strategy for risk minimization in epileptic patients on carbamazepine therapy: a randomized controlled trial .” 2. I have received an explanation of the nature, purpose, duration, and foreseeable effects and risks of the trial and what I will be expected to do. My questions have been answered satisfactorily. 3. I understand that my participation in the study is voluntary and that I may refuse to participate or may withdraw from the study at any time, without penalty or loss of benefits to which I am otherwise entitled. 4. I further understand that any information that becomes available during the course of the study that may affect my willingness to take part will be informed to me. 5. I give permission to allow the study personnel to withdraw my blood (5.0 ml) for the determination of genotyping and plasma carbamazepine levels. 6. Institutional ethics committee authorities may wish to examine my medical records to verify the information collected. By signing/giving a thumb impression on this document, I give permission for this review of my records. 7. I understand that my identity will not be revealed in any report or publication. 8. I agree to take part in the above study.

Supporting Institution

Seth GS Medical College & KEM Hospital, Mumbai, India

Project Number

EC/OA-41/2019

Thanks

We would like to thank to our present and past Head of Department and Dean of institute for their help and support for conducting this research work.

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