In this episode, I’ll discuss whether meropenem could theoretically work as an antidote for medications metabolized by UGT.
One of my favorite antidote stories is octreotide as an antidote for sulfonylureas. Because of octreotide’s mechanism of action inhibiting insulin release from the pancreas, it was successfully applied as an antidote to sulfonylurea toxicity to stop excessive sulfonylurea-induced pancreatic insulin release.
Applying similar logic, I wonder if meropenem could work as an antidote for toxicity from medications such as valproic acid?
Meropenem is known to interact with valproic acid, lowering valproic levels substantially. One of the theories for this interaction is the activation of UGT by meropenem. UGT is responsible for glucuronidation of valproic acid, and increased activity of UGT would lead to lower valproic acid levels. Anecdotally, I have witnessed this interaction in patients in the ICU several times, and it is virtually impossible to maintain a therapeutic valproic acid level, even with increased doses, when this interaction is present.
If this mechanism is correct, administration of meropenem in the setting of valproic acid toxicity would be expected to increase the glucuronidation of valproic acid and thereby lower plasma levels. Whether this would work or have any significant effects on patient outcomes is theoretical, and I cannot find any literature or case reports of this intentional combination.
If you have any thoughts on this combination or have used carbapenems to intentionally lower a patient’s valproic acid level, I would appreciate you leaving a note in the comment section below, or sending an email to joe@pharmacyjoe.com.
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https://onlinelibrary.wiley.com/doi/10.1111/jcpt.12705
https://pubmed.ncbi.nlm.nih.gov/31980292/
https://journal.chestnet.org/article/S0012-3692(20)32940-8/fulltext
Here in my country ( Chile) meropenem was used succesfully for treating VPA toxicity, as reported by a colleague
https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.medicina-intensiva.cl/congreso2019/pdf_tr/48.pdf&ved=2ahUKEwio8LXxwYnuAhUmIbkGHcsXCVQQFjAAegQIARAB&usg=AOvVaw2Ply2qFUvg83KYuC1I22cq ( Article in Spanish)
Fantastic, thank you for linking the report!
I’ve never done it, but in theory would buy into it.
there’s a couple case reports:
https://pubmed.ncbi.nlm.nih.gov/31980292/
https://pubmed.ncbi.nlm.nih.gov/29733112/
https://pubmed.ncbi.nlm.nih.gov/31500925/
Thank you for linking those reports!