A retrospective study of therapeutic drug monitoring of anti-epileptic drugs at a tertiary care hospital in India

Renuka Munshi, Belhekar M N, Taur S R

Renuka Munshi, Belhekar M N, Taur S R

Keywords: anti-epileptic drugs, serum concentration, therapeutic drug monitoring

Abstract

Background: Epilepsy is a chronic disease and the aim of drug therapy is to prevent seizures with minimal adverse effects. To achieve this, the dosage of the anti-epileptic drugs (AEDs) needs to be individualised. The present study throws light on how professionals knowledgeable in clinical epilepsy management, like neurologists and clinical pharmacologists, can use Therapeutic Drug Monitoring (TDM) to design individualised dosage regimens.
Objective: The aim of the present study was to assess the effectiveness of TDM services in enhancing patient care in epileptic patients in India.
Material and Methods: This retrospective observational study was carried out over a period of two years at a tertiary care hospital in India. TDM reports of patients regularly attending the Epilepsy and TDM OPDs at our hospital were analysed. Serum AED levels were interpreted as below, within and above the reference range. All analyses were carried out using EpiInfo version 7 and a p value < 0.05 was considered significant.
Results: A total 1016 patients with 1347 TDM requisitions were analysed. Almost 46% and 9% of all TDM requisitions were below and above the reference range, respectively. However, significantly higher proportion of TDM requisition was below reference range in the 2 or more AEDs group compared to monotherapy group. Only 36% of requisitions for suspected toxicity had serum concentration above reference range.
Discussion: The results of present study suggest the importance of routine TDM of AEDs in patients with seizures. Detection of non-compliance, toxicity and failure of adequate response because of below reference range drug levels highlights the utility of TDM of AEDs in patients with seizures.
Conclusion: TDM of AEDs is a well-established means of optimising epilepsy treatment, but inter-individual variation in clinical outcome should be kept in mind while attempting an adjustment of doses.

References

1. Das K, Banerjee M, Mondal GP, Devi LG, Singh OP, Mukherjee BB. Evaluation of Socio-economic Factors Causing Discontinuation of Epilepsy Treatment Resulting in Seizure Recurrence: A study in An Urban Epilepsy Clinic in India. Seizure.2007;16:601–7.
2. Sridharan R, Murthy BN. Prevalence and Pattern of Epilepsy in India. Epilepsia. 1999;40:631–6.
3. Bialer M. The Pharmacokinetics and Interactions of New Antiepileptic Drugs: An overview. Ther Drug Monit. 2005;27:722–6.
4. Perucca E. Clinical Pharmacokinetics of New Generation Antiepileptic Drugs at the Extremes of Age. ClinPharmacokinet. 2006;45:351–64.
5. Browne TR, Holmes GL. Management. In: Browne TR, Holmes GL, editors. Handbook of epilepsy. 4th ed. Philadelphia: Lippincott Williams and Wilkins. 2008. p. 151– 75.
6. Baker GA, Jacoby A, Buck D, Stalgis C, Monnet D. Quality of Life of People with Epilepsy: A European Study. Epilepsia. 1997;38:353–62.
7. Definition of TDM. International Association of Therapeutic Drug Monitoring and Clinical Toxicology [cited 31st August 2013]. Available from: http://www.iatdmct.org/index.php/ publisher/articleview/frmArticleID/138.
8. Patsalos PN, Berry DJ, Bourgeois BFD, Cloyd JC, Glauser TA, Johannessen SI, et al. Antiepileptic drugs- Best Practice Guidelines for Therapeutic Drug Monitoring: A Position Paper by the Sub Commission on Therapeutic Drug Monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49:1239-76.
9. Schuetz EG. Induction of Cytochromes P450. Curr Drug Metab. 2001;2:139-47.
10. Neels HM, Sierens AC, Naelaerts K, Scharpe SL, Hatfield GM, Lambert WE. Therapeutic Drug Monitoring of Old and Newer Anti-epileptic Drugs. ClinChem Lab Med. 2004;42:1228-55.
11. Bates DW, Soldin SJ, Rainey PM, Micelli JN. Strategies for Physician Education in Therapeutic Drug Monitoring. ClinChem. 1998;44:401-7.
12. Johannessen SI, Landmark CJ. Value of Therapeutic Drug Monitoring in Epilepsy. Expert Rev Neurother. 2008;8:929- 39.
13. John JT. IAP Policy on Age of Children for Pediatric Care. Indian Pediatrics. 1999;36:461-3
14. Yukawa E. Optimisation of Antiepileptic Therapy. The Importance of Serum Drug Concentration Monitoring. ClinPharmacokinet. 1996;31:120-30.
15. Garg SK, Gupta MC, Handu SS, Bhargava VK. Therapeutic Drug Monitoring of Antiepileptic Drugs- A Preliminary Experience. Indian J Pharmacol. 2000;32:28-30.
16. Dahiya K, Bansal P, Ghalaut VS, Dhankhar R, Ghalaut PS. Therapeutic Drug Monitoring for Antiepileptic Drugs Using HPLC: An Experience at a Tertiary Care Hospital in India. Neurol Asia. 2010;15:233-7.
17. Krishnan A, Sahariah SA, Kapoor SK. Cost of Epilepsy in Patients Attending a Secondary Level Hospital in India. Epilepsia. 2004;45:289-91.
18. Irshaid YM, Hamdi AA, Homrany MAI. Evaluation of Therapeutic Drug Monitoring of Antiepileptic Drugs. Int J ClinPharmacolTher. 2003;41:126-31.
19. KrasowskiMD. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications. Pharmaceuticals. (Basel) 2010;3:1909-35.
20. Richens A. Clinical Pharmacokinetics of Phenytoin. ClinPharmacokinet. 1979;4:153-69.
21. Patsalos PN, Perucca E. Clinically Important Drug Interactions in Epilepsy: General Features and Interaction between Antiepileptic Drugs. Lancet Neurol. 2003;2:347-56.
22. Johannessen SI, Landmark CJ. Antiepileptic Drug Interactions - Principles and Clinical Implications. CurrNeuropharmacol. 2010;8:254–67.
23. Woo E, Chan YM, Yu YL, Chan YW, Huang CY. If a Well-Stabilized Epileptic Patient Has a Sub therapeutic Antiepileptic Drug Level, Should the Dose be increased? A Randomized Prospective Study. Epilepsia. 1988;29:129-39.
24. Cloyd J, Birnbaum A, Musib L, Leppik I. Clinical Pharmacology of Phenytoin in the Elderly. Epilepsia. 2001;42:11-2.
25. Kudriakova TB, Sirota LA, Rozova GI, Gorkov VA. Auto Induction and Steady-State Pharmacokinetics of Carbamazepine and its Major Metabolites. Br J ClinPharmacol. 1992;33:611-5.
26. Adrian MB. Drug Interactions that Matter. Pharm J. 1999;262:325-7.
27. Tartara A, Galimberti CA, Manni R, Parietti L, Zucca C, Baasch H, et al. Differential Effects of ValproicAcid and Enzyme- Inducing Anticonvulsants on NimodipinePharmacokinetics in Epileptic Patients. Br J ClinPharmacol. 1991;32:335–40.
28. Perucca E, Richens A. Antiepileptic drugs: Clinical Aspects. In: Richens A, Marks V, editors. Therapeutic drug monitoring. Edinburgh: Churchill Livingstone. 1981. p. 320-48.
29. Bring P, Ensom MH. Does OxcarbazepineWarrantTherapeutic Drug Monitoring? A Critical Review. ClinPharmacokinet. 2008;47:767-78.
30. Mathew BS, Fleming DH, Thomas M, Prabha R, Saravanakumar K. An Initial Experience with Therapeutic Drug Monitoring of Levetiracetam as Reported from a Pediatric Clinical Setting in India. Neurol India. 2012; 60:146- 9.
31. Chong E, Dupuis LL. Therapeutic Drug Monitoring of Lamotrigine. Ann Pharmacother. 2002; 36:917-20.
32. Hussein A, Abdulgalil A, Omer F, Eltoum H, Hamad A, El-Adil O, et al. Correlation between Serum Level of Antiepileptic Drugs and their Side Effects. Oman Med J. 2010; 25:17-21.
33. Luders H, Acharya J, Baumgartner C, Benbadis S, Bleasel A, Burgess R, et al. Semiological Seizure Classification. Epilepsia. 1998; 39:1006-13.
34. Engel J Jr. Classifications of the International League against Epilepsy: Time for Reappraisal. Epilepsia. 1998; 39:1014-7.