Valproic Acid with Cisplatin Interaction Details
Brand Names Associated with Valproic Acid
- Depakene®
- Depakote®
- Depakote® ER
- Depakote® Sprinkle
- Divalproex sodium
- Valproate sodium
- Valproic Acid
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 08, 2023
Interaction Effect
Decreased valproic acid plasma concentrations and increased risk of seizures
Interaction Summary
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 diazepam. Anticonvulsant levels, including valproic acid, should be closely monitored in patients receiving CISplatin-containing antineoplastic therapy .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Anticonvulsant levels, including valproic acid, should be closely monitored in patients receiving antineoplastic therapy containing CISplatin. Doses of valproic acid may need to be increased.
Mechanism Of Interaction
Unknown
Literature Reports
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 .
Valproic Acid Overview
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Valproic acid is used alone or with other medications to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). It is also used to prevent migraine headaches but not to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. It works by increasing the amount of a certain natural substance in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
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Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.