Doripenem Injection and Valproic Acid: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Doripenem 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 for breakthrough seizures
Interaction Deep Dive
The concomitant use of doripenem and valproic acid may result in decreased valproic acid concentrations and a loss of seizure control2. In a study in 23 healthy volunteers, the concomitant administration of valproic acid and doripenem resulted in a reduction in the serum valproic acid level to below the therapeutic range of 50 to 100 mcg/mL, occurring 12 hours following coadministration 1. In 2 case reports, the concomitant use resulted in markedly decreased valproic acid trough concentrations, which rebounded following doripenem discontinuation 3. Frequently monitor valproic acid concentrations after starting doripenem. If valproic acid concentrations cannot be maintained within the therapeutic range or a seizure occurs, alternative antibiotic or supplemental anticonvulsant therapy should be considered 21. Based on case reports of this interaction, it is important to note that increasing valproic acid or sodium valproate dose may not result in increased valproic acid serum levels 1.
Why it happens (mechanism)
Unknown
Literature reports
2 reports — tap to read
a) A case report described markedly reduced valproic acid concentrations in 2 patients following the concomitant use of doripenem and valproic acid. The first case involved a 54-year-old woman, receiving divalproex sodium 750 mg once daily, who was prescribed doripenem 500 mg IV every 8 hours on day 3 of a hospital stay for exacerbation of COPD. Prior to doripenem initiation, the valproic acid concentration was measured at 42 mcg/mL. Despite bolus valproic acid doses on days 5, 6, and 7, the valproic acid trough concentrations remained between 11 and 16 mcg/mL. On day 6, doripenem was discontinued and on day 8 the valproic acid concentration increased to 47 mcg/mL and subsequently increased to 83 mcg/mL 1 week after discharge. The second case involved a 54-year-old female admitted to the hospital following a motor vehicle accident. She was receiving valproate sodium 1250 mg IV every 8 hours, with a valproic acid trough concentration of 62 mcg/mL, and was started on doripenem 500 mg IV every 8 hours for aspiration pneumonia. Approximately 36 hours following doripenem initiation, the valproic acid trough dropped to 19 mcg/mL and over the next several days, ranged between 12 and 19 mcg/mL. Despite the low valproic acid trough concentrations, this patient never experienced seizures, but expired on day 36 due to multiple traumas. In both cases, the interaction was rated as probable on the Drug Interaction Probability Scale 3.
b) In a study in 23 healthy volunteers, the concomitant administration of valproic acid and doripenem resulted in a reduction in the serum valproic acid level to below the therapeutic range of 50 to 100 mcg/mL, occurring 12 hours following coadministration. Patients received doripenem 500 mg every 8 hours for 4 doses while concomitantly receiving valproic acid 500 mg every 12 hours for 7 days. The mean Cmax of valproic acid decreased by 44.5% and the mean Cmin by 77.7% when the 2 drugs were coadministered compared with administration of valproic acid alone; the mean AUC of valproic acid also decreased by 63%. Notably, Cmax of the glucuronide metabolite of valproic acid increased by 62.6% and 50%, respectively 1.
Common questions
Can I take Doripenem Injection and Valproic Acid together?
Reduced valproic acid exposure and increased risk for breakthrough seizures Always confirm with your pharmacist or prescriber before making any change.
How serious is the Doripenem Injection and Valproic Acid interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Doripenem Injection or Valproic Acid 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 (3)
- Product Information: DORIBAX(R) intravenous infusion powder for solution, doripenem intravenous infusion powder for solution. Ortho-McNeil-Janssen Pharmaceuticals, Inc (Per FDA), Raritan, NJ, 2012.
- Product Information: Depakote oral delayed-release tablets, divalproex sodium oral delayed-release tablets. AbbVie Inc (per manufacturer), North Chicago, IL, 2023. DailyMed
- Hellwig TR, Onisk ML, & Chapman BA: Potential interaction between valproic acid and doripenem. Curr Drug Saf 2011; 6(1):54-58. PubMed
Keep reading about Doripenem Injection
Keep reading about Valproic Acid
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist