Valproic Acid with Doripenem 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 for breakthrough seizures
Interaction Summary
The concomitant use of doripenem and valproic acid may result in decreased valproic acid concentrations and a loss of seizure control. 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 . In 2 case reports, the concomitant use resulted in markedly decreased valproic acid trough concentrations, which rebounded following doripenem discontinuation . 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 . 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 .
Severity
Major
Onset
Rapid
Evidence
Established
How To Manage Interaction
Frequently monitor valproic acid concentrations after starting doripenem as coadministration may result in reduced valproic acid concentrations and possibly a loss of seizure control. If valproic acid concentrations cannot be maintained within the therapeutic range or a seizure occurs, alternative antibiotic or supplemental anticonvulsant therapy should be considered; however, increasing valproic acid or sodium valproate dose may not necessarily result in increased valproic acid serum levels.
Mechanism Of Interaction
Unknown
Literature Reports
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 .
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 .
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.