Valproic Acid with Betamipron 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 efficacy of valproic acid
Interaction Summary
Concomitant use of valproic acid with carbapenem antibiotics such as panipenem/betamipron may result in clinically significant reduction in serum valproic acid concentration and may result in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop significantly or seizure control deteriorates. Three case reports describe a decrease in valproic acid serum concentrations when panipenem/betamipron therapy was instituted, resulting in the recurrence of seizures in two patients. Although the exact mechanism of this interaction is not known, panipenem/betamipron should be avoided in patients treated with valproic acid .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of valproic acid with carbapenem antibiotics such as panipenem/betamipron may result in clinically significant reduction in serum valproic acid concentration and may result in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop significantly or seizure control deteriorates.
Mechanism Of Interaction
Unknown
Literature Reports
A) A 4-year-old female with spastic quadriplegia, epilepsy, and mental retardation was receiving valproic acid 25 mg/kg/day and phenobarbital 5 mg/kg/day with serum levels of 55.1 mg/dL and 28.4 mg/dL, respectively. She was admitted to the hospital for pneumonia, and her valproic acid dose was increased to 30 mg/kg/day while the phenobarbital was decreased to 4.5 mg/kg/day. Panipenem/betamipron therapy was initiated at 60 mg/kg/day in three divided doses daily, and the serum valproic acid level decreased to 22.9 mg/mL by day 6. Although no seizures developed as a result of this decrease, panipenem/betamipron was discontinued, and the valproic acid serum concentration increased to 72.6 mg/dL .
B) A 3-year-old girl with quadriplegia, epilepsy, and mental retardation was receiving valproic acid 35 mg/kg/day, carbamazepine 11 mg/kg/day, and phenytoin 10 mg/kg/day for two months before a hospital admission for aspiration pneumonia. Valproic acid serum concentration was 88.7 mg/mL prior to the start of panipenem/betamipron 60 mg/kg/day and amikacin 5 mg/kg/day. Three days later, generalized tonic-clonic seizures began to occur once or twice daily. The valproic acid level had decreased to 30.9 mg/mL and further dropped to 26.8 mg/mL two days later. Despite an increase in the valproic acid dose to 42 mg/kg/day, the serum concentration continued to decrease to 15.3 mg/mL on day 8 of treatment with panipenem/betamipron. The valproic acid level started to increase within 24 hours of discontinuing panipenem/betamipron. The phenytoin serum level was undetectable on day 3 of panipenem/betamipron therapy, but the carbamazepine level was not significantly altered .
C) Panipenem/betamipron 30 mg/kg/day resulted in intense, generalized seizures and frequent myoclonic seizures in a 22-year-old male who had previously been stabilized on valproic acid 32 mg/kg/day, clonazepam 0.9 mg/kg/day, and phenytoin 5 mg/kg/day. Prior to panipenem/betamipron therapy, his valproic acid serum level ranged from 78.7 mg/mL to 108.9 mg/mL. However, by day 5 of panipenem/betamipron treatment, the valproic acid level was 26.7 mg/mL. Although the valproic acid dose was increased to 34 mg/kg/day, serum levels were undetectable by day 25 of panipenem/betamipron therapy. After the antibiotic was discontinued, the serum valproic acid concentration increased to 55 mg/mL and the frequency of the seizures was decreased. Incidentally, in this patient, the phenytoin and clonazepam levels were not significantly altered by the presence of panipenem/betamipron .
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.
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.