Valproic Acid and Ertapenem Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ertapenem Injection
Valproic Acid
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced valproic acid exposure and increased risk of seizures and status epilepticus
Interaction Deep Dive
The concomitant use of ertapenem (carbapenem) and valproic acid (VPA) or divalproex sodium is generally not recommended as this may cause decreased VPA plasma concentrations and increase the risk for breakthrough seizures. Increasing the VPA or divalproex sodium dose may not be adequate to achieve desired levels. Consider using an alternative antibiotic (other than a carbapenem) which does not affect VPA serum levels. If concomitant administration is unavoidable, consider supplemental anticonvulsant therapy12. Consider alternative antibacterial or anticonvulsant therapy if serum valproic acid concentrations drop significantly or seizure control deteriorates 3. And, consider therapeutic drug monitoring of VPA and free VPA serum concentrations, especially when initiating or discontinuing carbapenems 4.
Why it happens (mechanism)
Unknown
Literature reports
3 reports — tap to read
a) In a 10-year retrospective study, concomitant use of valproic acid and a carbapenem (imipenem/cilastatin n=46; meropenem n=68, or ertapenem n=48) resulted in a subtherapeutic VPA serum level (50 mcg/mL) in 92% of patients. The VPA serum concentration significantly decreased by 69.1% with ertapenem and by 65.2% with meropenem, while a nonsignificant decrease of 11.9% occurred with imipenem/cilastatin. A decrease in VPA serum levels during concomitant therapy was associated with a significant increased risk of seizures (OR, 0.96 [95% CI, 0.95 to 0.98]) and a nonsignificant increase in status epilepticus (OR, 0.98 [95% CI, 0.96 to 1]) 4.
b) A 41-year-old man maintained on divalproex sodium for seizure prophylaxis experienced recurrent tonic-clonic seizures on day 7 of concomitant ertapenem 1000 mg every 24 hours. Medical history was significant for hypertension controlled with metoprolol, seizure disorder secondary to traumatic brain injury, and chronic cranial osteomyelitis. Approximately 3 months prior to starting ertapenem, the patient's serum VPA concentration was therapeutic at 130 mcg/mL while taking divalproex sodium 2000 mg/day. He was admitted following 3 seizure episodes, the last of which was a witnessed tonic-clonic seizure lasting longer than 1 minute. The serum VPA concentration was 70 mcg/mL. The dose of divalproex sodium was increased to 2750 mg/day and the patient was discharged. He returned 4 days later with recurrent seizures and a serum VPA concentration of 10.7 mcg/mL. Valproic acid 1000 mg IV was administered along with 1 oral dose of divalproex sodium 100 mg, ertapenem was discontinued, and ampicillin-sulbactam 3 grams IV every 6 hours was begun. The following day the patient's serum VPA concentration increased to 55 mcg/mL. Oral divalproex sodium was increased to 4500 mg/day, and 2 days later his level was 88.1 mcg/mL. Five days after ertapenem was discontinued his serum VPA concentration reached 146 mcg/mL, necessitating a decrease in divalproex sodium dose. He subsequently remained seizure-free 56.
c) An 80-year-old woman, chronically treated with valproic acid solution 1100 mg/day for complex partial seizures secondary to severe cerebrovascular disease, experienced significantly reduced serum valproic acid concentrations beginning 4 days after the initiation of ertapenem 1000 mg every 24 hours. Approximately, 1.5 months prior to ertapenem exposure, her total serum valproic acid concentration was 72 mcg/mL. Admitted to the hospital for aspiration pneumonia, the patient was treated with ertapenem. Four days later serum valproic acid concentration was reported to be 36.4 mcg/mL, and her valproic acid dose was increased to 1600 mg/day. Two days later serum valproic acid measured 18.42 mcg/mL and the drug dose increased to 2000 mg/day. A level of 1.04 mcg/mL was measured 4 days after this dose increase. Ertapenem was discontinued. With intravenous administration of valproic acid (800 mg loading dose followed by 400 mg every 6 hours), the patient's serum concentration gradually returned to therapeutic range over the next 11 days. She was subsequently maintained on oral valproic acid 1400 mg/day 7.
Common questions
Can I take Valproic Acid and Ertapenem Injection together?
Reduced valproic acid exposure and increased risk of seizures and status epilepticus Always confirm with your pharmacist or prescriber before making any change.
How serious is the Valproic Acid and Ertapenem Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Valproic Acid or Ertapenem Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (7)
- Product Information: INVANZ(R) intravenous injection, intramuscular injection, ertapenem intravenous injection, intramuscular injection. Merck Sharp & Dohme Corp. (per manufacturer), Whitehouse Station, NJ, 2013. DailyMed
- Product Information: Depakote oral delayed-release tablets, divalproex sodium oral delayed-release tablets. AbbVie Inc (per manufacturer), North Chicago, IL, 2023. DailyMed
- Product Information: STAVZOR® oral delayed release capsules, valproic acid oral delayed release capsules. Bionpharma Inc, Princeton, NJ, 2026. DailyMed
- Chen I-L, Lee C-H, Hsiao S-C, et al: Interactions between carbapenems and valproic acid among the patients in the intensive care units. J Crit Care 2021; 62:151-156. PubMed
- Lunde JL, Nelson RE, & Storandt HF: Acute seizures in a patient receiving divalproex sodium after starting ertapenem therapy. Pharmacotherapy 2007; 27(8):1202-1205. DOI
- Pers Comm, 2008
- CabanesMariscal MA, Sanchez LopezP, Alvarez HerranzP, et al: Pharmacokinetic interaction between valproic acid and ertapenem. Farm.Hosp 2006; 30(5):313-315. PubMed
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