Valproic Acid with Imipenem 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
Reduced valproic acid exposure and increased risk of seizures and status epilepticus
Interaction Summary
Significant reductions in serum valproic acid (VPA) levels have been reported in patients receiving carbapenem antibiotics (imipenem/cilastatin, meropenem, or ertapenem) concomitantly with valproic acid which resulted in a significant increase in the risk of seizures and a nonsignificant increase in the risk of status epilepticus in a 10-year retrospective study. Concomitant use of valproic acid and a carbapenem resulted in a subtherapeutic VPA serum level (50 mcg/mL) in 92% of patients. The VPA serum concentration decreased by 11.9% with imipenem (nonsignificant). Concomitant use of carbapenems, including imipenem, and valproic acid or divalproex sodium is generally not recommended. Increasing the valproic acid or divalproex sodium dose may not be adequate to achieve desired levels. Alternative antibiotic therapy should be considered in a patient whose seizures are well-controlled on valproic acid. If concomitant administration is required, supplemental anticonvulsant therapy should be considered and consider therapeutic drug monitoring of VPA and free VPA serum concentrations, especially when initiating or discontinuing carbapenems .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Coadministration of imipenem and valproic acid or divalproex sodium is generally not recommended as this has resulted in reduced serum valproic acid levels and an increased risk of seizures in case reports. Increasing the valproic acid dose may not be adequate to achieve desired levels. Alternative antibiotic therapy should be considered in a patient whose seizures are well-controlled on valproic acid. If concomitant administration is required, consider supplemental anticonvulsant therapy and consider therapeutic drug monitoring of VPA and free VPA serum concentrations, especially when initiating or discontinuing carbapenems .
Mechanism Of Interaction
Unknown
Literature Reports
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 valproic acid (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]) .
Valproic Acid Overview
-
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.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.
Where Does Our Information Come From?
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.