Aspirin with Valproic Acid Interaction Details

Brand Names Associated with Aspirin

Brand Names Associated with Valproic Acid

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased valproic acid exposure

Interaction Summary

Use caution while using aspirin and valproic acid concomitantly. During coadministration, aspirin can displace protein-bound valproic acid and may result in increased serum valproic acid levels[1][2]. Salicylates have been shown to alter both the metabolism and protein binding of valproic acid. This has resulted in increased free valproate free fractions [3] by 30% to 65% [4][5].

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Use caution while using aspirin and valproic acid concomitantly. During coadministration, aspirin can displace protein-bound valproic acid and may result in increased serum valproic acid levels[1][2].

Mechanism Of Interaction

Displacement of valproic acid from plasma protein binding sites

Literature Reports

A) Six epileptic children who were taking valproic acid received antipyretic doses of aspirin. The steady-state free fraction of valproate rose from 12% to 43% in the presence of salicylate in five of these patients. Half-life of valproate, based upon total and free valproate concentrations, increased. Renal excretion of unchanged valproate decreased with salicylates. Salicylates appear to displace valproate from serum protein binding sites and alter valproate metabolism [6][7].

B) A study involving the coadministration of aspirin at antipyretic doses (11 to 16 mg/kg) with valproate to six pediatric patients revealed a decrease in protein binding and an inhibition of metabolism of valproate. Valproate free fraction was increased 4-fold in the presence of aspirin compared to valproate alone. The beta-oxidation pathway consisting of 2-E-valproic acid, 3-OH valproic acid, and 3-keto valproic acid was decreased from 25% of total metabolites excreted on valproate alone to 8.3% in the presence of aspirin [2].

References

1 ) Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021.

2 ) Product Information: Depakote oral delayed-release tablets, divalproex sodium oral delayed-release tablets. AbbVie Inc (per manufacturer), North Chicago, IL, 2023.

3 ) Product Information: Depakote(R) ER, divalproex sodium extended-release tablets. Abbott Laboratories, North Chicago, IL, 2003.

4 ) Abbott FS, Kassam J, Orr JM, et al: The effect of aspirin on valproic acid metabolism. Clin Pharmacol Ther 1986; 40:94-100.

5 ) Goulden KJ, Dooley JM, Camfield PR, et al: Clinical valproate toxicity induced by acetylsalicylic acid. Neurology 1987; 37:1392-1394.

6 ) Orr JM, Abbott FS, Farrell K, et al: Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects. Clin Pharmacol Ther 1982; 31:642-649.

7 ) Farrell K, Orr JM, Abbott FS, et al: The effect of acetylsalicylic acid on serum free valproate concentrations and valproate clearance in children. J Pediatr 1982; 101:142-144.

Aspirin Overview

• Prescription aspirin is used to relieve the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints), osteoarthritis (arthritis caused by breakdown of the lining of the joints), systemic lupus erythematosus (condition in which the immune system attacks the joints and organs and causes pain and swelling) and certain other rheumatologic conditions (conditions in which the immune system attacks parts of the body). Nonprescription aspirin is used to reduce fever and to relieve mild to moderate pain from headaches, menstrual periods, arthritis, toothaches, and muscle aches. Nonprescription aspirin is also used to prevent heart attacks in people who have had a heart attack in the past or who have angina (chest pain that occurs when the heart does not get enough oxygen). Nonprescription aspirin is also used to reduce the risk of death in people who are experiencing or who have recently experienced a heart attack. Nonprescription aspirin is also used to prevent ischemic strokes (strokes that occur when a blood clot blocks the flow of blood to the brain) or mini-strokes (strokes that occur when the flow of blood to the brain is blocked for a short time) in people who have had this type of stroke or mini-stroke in the past. Aspirin will not prevent hemorrhagic strokes (strokes caused by bleeding in the brain). Aspirin is in a group of medications called salicylates. It works by stopping the production of certain natural substances that cause fever, pain, swelling, and blood clots.

• Aspirin is also available in combination with other medications such as antacids, pain relievers, and cough and cold medications. This monograph only includes information about the use of aspirin alone. If you are taking a combination product, read the information on the package or prescription label or ask your doctor or pharmacist for more information.

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.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.