Six critically ill patients given a carbapenem antibiotic lost 58 percent of their valproate level; five had seizures
Mean valproate trough fell from 51.7 to 21.8 mg per litre when meropenem, imipenem or ertapenem was added; clearance rose 191 percent. Every level during co-treatment was "below the lower boundary of the usual therapeutic range."
Weak or heavily disputed. Treat as a question, not an answer. how we score evidence
Caveat on this rating: A case series of six intensive-care patients; seizures in critically ill people have many causes and the series cannot apportion them. The direction and size of the level drop are consistent across the literature the authors reviewed.
The valproate label says monitor levels with carbapenem antibiotics. This is what the levels did.
Significant findings
Tobin and colleagues (Drug Metabolism and Drug Interactions, 2009) reviewed hospitalised adults on valproic acid (VPA) who received a carbapenem and had serial levels. "Six critically ill VPA-treated patients were identified who concurrently received meropenem (n=4), imipenem (n=1), or ertapenem (n=1). As compared with values obtained while not receiving treatment with the carbapenem, mean plasma VPA trough concentrations decreased by 58% (from 51.7 [95% confidence interval {CI} 28.0-75.4] to 21.8 [95% CI 11.1-32.5] mg/L; p = 0.025). Estimated mean VPA clearance increased by 191%".
"All VPA concentrations measured during concurrent VPA-carbapenem treatment were below the lower boundary of the usual therapeutic range. Five patients (83%) experienced generalized seizures during concurrent VPA-carbapenem treatment, including two with no prior history of seizures or epilepsy." Their conclusion: "Concurrent use of these medications should be avoided."
A separate review by Mancl and Gidal (Annals of Pharmacotherapy, 2009), read for this wave, describes the mechanism as several at once: carbapenems block the gut transporter that absorbs valproate, reduce its recycling from the gut, shift it into red blood cells, and speed its breakdown; in animals a single carbapenem cut absorption of oral valproate by 57 percent.
Worth asking
Six patients is a case series, not a trial, and these were people already ill enough for intensive care. The reason it belongs here is that the interaction is large, fast and mechanistically unusual, and the antibiotic is chosen by a different team from the one that prescribed the valproate. If you take valproate for mood and are admitted with a serious infection, the question for the admitting team is whether the antibiotic is a carbapenem, and if so what the plan for the valproate is.
Source
Valproic acid-carbapenem interaction: report of six cases and a review of the literature — Tobin JK, Golightly LK, Kick SD, Jones MA (2009)
Indexed peer-reviewed journal
Read the source: https://doi.org/10.1515/dmdi.2009.24.2-4.153
DOI: 10.1515/dmdi.2009.24.2-4.153
How this was scored
- Study design
- Case series or case report
- Funding
- Funding not disclosed
- Published in
- Indexed peer-reviewed journal
- Sample size
- 6
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "contested". Weak or heavily disputed. Treat as a question, not an answer. It scores 28 out of 100 on our published rubric. One caveat travels with that badge: A case series of six intensive-care patients; seizures in critically ill people have many causes and the series cannot apportion them. The direction and size of the level drop are consistent across the literature the authors reviewed. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Valproic acid-carbapenem interaction: report of six cases and a review of the literature — Tobin JK, Golightly LK, Kick SD, Jones MA (2009). Published in: Indexed peer-reviewed journal. DOI: 10.1515/dmdi.2009.24.2-4.153. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Case series or case report. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.