A clinical pharmacist's intervention on interaction between meropenem and valproic acid in paediatric inpatient clinic: A case report

Abstract

Background and Aims: Drug-drug interactions cause many complex drug events, especially adverse drug effects. It is known that drug interactions occur when meropenem and valproic acid are used together. It was aimed to back up existing research on the interaction of valproic acid. Methods: After an interaction had been suspected by the ward pharmacists, all of the patient’s drugs were assessed via Up- ToDate® and Micromedex® databases and the interaction management was shared with the physician in charge. Results: The patient’s serum valproic acid through level was in therapeutic range before meropenem administration. After the administration of meropenem, the patient's number of seizures increased and the serum trough level of valproic acid de- creased to 4.3 µg/ml. The valproic acid levels turned back to normal range after switching to a carbapenem antibiotic. Conclusion: Drug interactions are often encountered in paediatric patients and it is of critical importance in terms of seizure control. Because of the drug interaction between valproic acid and meropenem, one should avoid using these medications concomitantly. If that is impossible, daily serum valproic acid levels should be monitored with caution. Clinical pharmacists could increase the clinicians’ awareness about drug-drug interactions.

Keywords

• drug interactions
• hospitalized child
• meropenem
• pharmacists
• valproic acid

References

1. Al-Quteimat, O., & Laila, A. (2020). Valproate Interaction With Car- bapenems: Review and Recommendations. Hospital Pharmacy, 55(3), 181-187. doi:10.1177/0018578719831974
2. Coves-Orts, F. J., Borras-Blasco, J., Navarro-Ruiz, A., Murcia-Lopez, A., & Palacios-Ortega, F. (2005). Acute seizures due to a probable interaction between valproic acid and meropenem. Annals of Pharmacotherapy, 39(3), 533-537. doi:10.1345/aph.1E358
3. González, C., & Villena, R. (2012). Interacción entre merope- nem y ácido valproico: A propósito de dos casos pediátricos. Revista chilena de infectología, 29, 353-355. Retrieved from http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716- 10182012000300018&nrm=iso
4. Miranda Herrero, M. C., Alcaraz Romero, A. J., Escudero Vilaplana, V., Fernandez Lafever, S. N., Fernandez-Llamazares, C. M., Barredo Valderrama, E., . . . de Castro, P. (2015). Pharmacological interaction between valproic acid and carbapenem: what about levels in pe- diatrics? European Journal of Paediatric Neurology, 19(2), 155-161. doi:10.1016/j.ejpn.2014.12.010
5. Nakamura, Y., Nakahira, K., & Mizutani, T. (2008). Decreased valproate level caused by VPA-glucuronidase inhibition by car- bapenem antibiotics. Drug Metabolism Letters, 2(4), 280-285. doi:10.2174/187231208786734049
6. Naranjo, C. A., Busto, U., Sellers, E. M., Sandor, P., Ruiz, I., Roberts, E. A., . . . Greenblatt, D. J. (1981). A method for estimating the prob- ability of adverse drug reactions. Clinical Pharmacology & Thera- peutics, 30(2), 239-245. doi:10.1038/clpt.1981.154
7. Okumura, L. M., Andreolio, C., Di Giorgio, C., Carvalho, P. R. A., & Piva, J. P. (2017). Meropenem-induced low valproate levels in a ce- rebral palsy child. The Brazilian Journal of Infectious Diseases, 21(4),491. doi:10.1016/j.bjid.2017.01.010
8. Park, M. K., Lim, K. S., Kim, T. E., Han, H. K., Yi, S. J., Shin, K. H., . . .Yu, K. S. (2012). Reduced valproic acid serum concentrations due to drug interactions with carbapenem antibiotics: overview of 6 cases. Therapeutic Drug Monitoring, 34(5), 599-603. doi:10.1097/ FTD.0b013e318260f7b3

9. Spriet, I., Goyens, J., Meersseman, W., Wilmer, A., Willems, L., & Van Paesschen, W. (2007). Interaction between valproate and me- ropenem: a retrospective study. Annals of Pharmacotherapy, 41(7), 1130-1136. doi:10.1345/aph.1K079
10. Wu, C. C., Pai, T. Y., Hsiao, F. Y., Shen, L. J., & Wu, F. L. (2016). The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/ Cilastatin, and Meropenem) on Serum Valproic Acid Concentra- tions. Therapeutic Drug Monitoring, 38(5), 587-592. doi:10.1097/ FTD.0000000000000316
11. Yamamura, N., Imura-Miyoshi, K., & Naganuma, H. (2000). Panipe- num, a carbapenem antibiotic, increases the level of hepatic UDP-glucuronic acid in rats. Drug Metabolism and Disposition, 28(12), 1484-1486. Retrieved from https://www.ncbi.nlm.nih.gov/ pubmed/11095587