Cisplatin Injection and Valproic Acid: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Valproic Acid
Cisplatin Injection
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
Decreased valproic acid plasma concentrations and increased risk of seizures
Interaction Deep Dive
Coadministration of CISplatin and valproic acid may result in decreased valproic acid concentrations and an increased risk of seizures. In a case report, a patient receiving CISplatin-based chemotherapy for testicular cancer experienced an approximate 50% reduction in valproic acid levels 7 weeks after the first chemotherapy administration that resulted in severe generalized tonic-clonic seizures and required medical management with phenytoin and diazepam2. Anticonvulsant levels, including valproic acid, should be closely monitored in patients receiving CISplatin-containing antineoplastic therapy 1.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) A 34-year-old man with epilepsy stabilized with valproic acid and phenytoin experienced severe generalized tonic-clonic seizures, which required treatment with phenytoin 250 mg and diazepam 10 mg, 7 weeks following administration of the first CISplatin-based chemotherapy for testicular cancer. The patient's epilepsy had been controlled with valproic acid (baseline serum level 90 to 100 mcg/mL) and phenytoin when a chemotherapy regimen was initiated, including bleomycin 30 mg/day on day 1, cisplatin 33 mg/day on days 2 to 6, and etoposide 124 mg/day on days 2 to 6 (BEP). At the time of the seizures, the valproic acid level was found to be approximately 50% lower than baseline. Oral phenytoin was resumed 100 mg 3 times daily. Following completion of 4 BEP cycles, each causing seizures associated with decreased valproic acid levels, the patient was switched to a regimen including paclitaxel 240 mg/day on day 1, ifosfamide 1800 mg/day on days 2 to 5, and CISplatin 30 mg/day on days 2 to 5 for his cancer treatment (TIP). The patient continued to experience generalized tonic-clonic seizures; however, when the patient experienced seizure aura, he was treated with premedication consisting of IV phenytoin 125 mg and diazepam 5 mg. The patient was discharged from the hospital with resolution of testicular cancer approximately 10 months after his first round of BEP therapy and was maintained on valproic acid and phenytoin throughout all rounds of chemotherapy 2.
Common questions
Can I take Cisplatin Injection and Valproic Acid together?
Decreased valproic acid plasma concentrations and increased risk of seizures Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cisplatin 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 "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Cisplatin 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 (2)
- Product Information: PLATINOL(R)-AQ intravenous concentrate for injection, cisplatin intravenous concentrate for injection. Weylchem US Inc. (per FDA), Elgin, SC, 2011. DailyMed
- Ikeda H, Murakami T, Takano M, et al: Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient. Br J Clin Pharmacol 2005; 59(5):593-597. PubMed
Keep reading about Valproic Acid
Keep reading about Cisplatin Injection
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