A Life Saving Drug-Drug Interaction

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Rachel Rafeq
Emergency medicine pharmacist and toxicology enthusiast. Trained in medication safety and I apply that to everything. I love photography and world schooling my kids.

The Pre-brief

Valproic acid is a broad-spectrum antiepileptic medication used to treat bipolar disorder, focal (partial) onset, and generalized onset seizures. While standard therapy in overdose involves the use of activated charcoal and levocarnitine, the interaction between carbapenem antibiotics and valproic acid has been effective in quickly reducing serum VPA levels. 

Have you used a carbapenem to manage VPA toxicity? Let us know in the comments below!

The Debrief

  • A well-described drug-drug interaction exists between carbapenem antibiotics and valproic acid and therefore the combination should be avoided outside of a toxicological circumstance
  • Meropenem and ertapenem have been documented to reduce serum VPA levels up to 90% and therefore may be a unique method to treat valproic acid overdose  
  • The benefits of a short course of antibiotics may outweigh the risks related to antimicrobial stewardship
  • Carbapenems should not replace standard therapy but may be an excellent adjunct 
  • No specific Meropenem or Ertapenem dosing strategy has been recommended 

References

  1. Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online, Hudson, Ohio: UpToDate, Inc.; 2013; April 15, 2013
  2. Doyon S. Antiepileptics. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill; Accessed January 26, 2021. https://accessemergencymedicine.mhmedical.com/content.aspx?bookid=2569&sectionid=210272255
  3. Khobrani MA, Dudley SW, Huckleberry YC, et al. Intentional use of carbapenem antibiotics for valproic acid toxicity: A case report. J Clin Pharm Ther. 2018;43(5):723-725. doi:10.1111/jcpt.12705
  4. Divalproex sodium [package insert]. North Chicago, IL; Abbot Laboratories; January 2020
  5. Dreucean D, Beres K, McNierney-Moore A, Gravino D. Use of meropenem to treat valproic acid overdose. Am J Emerg Med. 2019;37(11):2120.e5-2120.e7. doi:10.1016/j.ajem.2019.158426
  6. Thomas C, Priano J, Smith TL. Meropenem as an antidote for intentional valproic acid overdose. Am J Emerg Med. 2020;38(3):690.e1-690.e2. doi:10.1016/j.ajem.2019.09.011
  7. Miller AD, Ball AM, Bookstaver PB, Dornblaser EK, Bennett CL. Epileptogenic potential of carbapenem agents: mechanism of action, seizure rates, and clinical considerations. Pharmacotherapy. 2011;31(4):408-423. doi:10.1592/phco.31.4.408

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