Aspirin with Mefenamic Acid Interaction Details

Brand Names Associated with Aspirin

Brand Names Associated with Mefenamic Acid

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

Interaction Effect

An increased risk of bleeding, decreased renal function, and an increased risk of gastrointestinal adverse events

Interaction Summary

Analgesic-dose aspirin is generally not recommended with an NSAID due to an increased risk of bleeding and/or gastrointestinal (GI) adverse events[1][2]. Concurrent use of aspirin with NSAIDs may also lead to decreased renal function [3]. Some NSAIDs (eg, ibuprofen, naproxen) can interfere with the antiplatelet activity of aspirin and as this may lead to an increased risk of cardiovascular events, consider use of an NSAID that does not interfere with the antiplatelet effect, or use a non-NSAID analgesic, as appropriate [4][5]. When using low-dose aspirin for prophylaxis of cardiovascular adverse events, consider monitoring more closely for GI bleeding [6].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Analgesic-dose aspirin is generally not recommended with an NSAID due to an increased risk of bleeding and/or gastrointestinal (GI) adverse events[1][2]. Concurrent use of aspirin with NSAIDs may also lead to decreased renal function [3]. Some NSAIDs (eg, ibuprofen, naproxen) can interfere with the antiplatelet activity of aspirin and as this may lead to an increased risk of cardiovascular events, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or use a non-NSAID analgesic, as appropriate [4][5]. When using low-dose aspirin for prophylaxis of cardiovascular adverse events, consider monitoring more closely for GI bleeding [6].

Mechanism Of Interaction

Additive effects on hemostasis; additive gastrointestinal adverse effects

Literature Reports

A) Ibuprofen 400 mg once daily 2 hours prior to immediate-release aspirin 81 mg for 6 days, showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane B2 (TxB2) inhibition at 24 hours after the day-6 aspirin dose [53%]. A lesser interaction was observed when ibuprofen 400 mg once daily was given 8 hours prior to immediate-release aspirin [90.7%]. There was no interaction when ibuprofen 400 mg once daily was given 2 hours after the immediate-release aspirin dose [99.2%]. In another study, immediate-release aspirin 81 mg once daily with ibuprofen 400 mg 3 times daily (1, 7, and 13 hours post-aspirin dose) for 10 consecutive days, the mean % serum TxB2 inhibition showed no interaction with the antiplatelet activity of aspirin [98.3%]. However, there were individual subjects with serum TxB2 inhibition below 95%; the lowest was 90.2%. A similar study with enteric-coated aspirin 81 mg once daily for 6 days and ibuprofen 400 mg 3 times daily (2, 7 and 12 hours post-aspirin dose) for 6 days showed an interaction with the antiplatelet activity at 24 hours following the day-6 aspirin dose [67%] [4].

B) Lower dose naproxen (220 mg daily or 220 mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. It is expected that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the this study due to the longer washout period [7][8][9][10][11].

C) In 2 studies in healthy volunteers, and in patients with osteoarthritis and established heart disease respectively, celecoxib (200 mg to 400 mg daily) has demonstrated a lack of interference with the cardioprotective antiplatelet effect of aspirin (100 mg to 325 mg) [2].

D) Certain NSAIDs, including ibuprofen [12], piroxicam, mefenamic acid, flufenamic acid, sulindac, and propyphenazone, can interfere with the irreversible platelet inhibition effects of aspirin via competition at the platelet cyclooxygenase-1 (COX-1) binding site. During in-vitro studies, platelet thromboxane was formed in the presence of aspirin and certain NSAIDs at clinically-relevant concentrations, compared with no thromboxane formation with aspirin alone. Single doses of NSAIDs used for treatment of acute pain are not likely to interact. There may be less interaction potential with acetaminophen, diclofenac, or ketoprofen [13].

E) The concomitant administration of aspirin with sulindac significantly depressed the plasma levels of the active sulfide metabolite. A double-blind study compared the safety and efficacy of sulindac 300 or 400 mg daily given alone or with aspirin 2.4 g/day for the treatment of osteoarthritis. The addition of aspirin did not alter the types of clinical or laboratory adverse experiences for sulindac; however, the combination showed an increase in the incidence of gastrointestinal adverse effects. Since the addition of aspirin did not have a favorable effect on the therapeutic response to sulindac, the combination is not recommended [14].

References

1 ) Product Information: ZORVOLEX(R) oral capsules, diclofenac oral capsules. Zyla Life Sciences US Inc (per FDA), Wayne, PA, 2021.

2 ) Product Information: CELEBREX(R) oral capsules, celecoxib oral capsules. GD Searle LLC (per FDA), New York, NY, 2019.

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

4 ) Product Information: CALDOLOR(R) intravenous injection, ibuprofen intravenous injection. Cumberland Pharmaceuticals Inc (per FDA), Nashville, TN, 2021.

5 ) Product Information: NAPROSYN(R) oral tablets, naproxen oral tablets. Canton Laboratories LLC (per FDA), Alpharetta, GA, 2021.

6 ) Product Information: TIVORBEX(R) oral capsules, indomethacin oral capsules. Iroko Pharmaceuticals LLC (per FDA), Philadelphia, PA, 2016.

7 ) Product Information: EC-NAPROSYN(R) oral delayed-release tablets, naproxen oral delayed-release tablets. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2019.

8 ) Product Information: ANAPROX(R) DS oral tablets, naproxen sodium oral tablets. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2019.

9 ) Product Information: NAPROSYN(R) oral tablets, naproxen oral tablets. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2019.

10 ) Product Information: NAPROSYN oral suspension, naproxen oral suspension. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2019.

11 ) Product Information: NAPRELAN(R) oral controlled-release tablets, naproxen sodium oral controlled-release tablets. Almatica Pharma, Inc. (per FDA), Morristown, NJ, 2019.

12 ) Product Information: DURLAZA(TM) oral extended release capsules, aspirin oral extended release capsules. New Haven Pharmaceuticals (per manufacturer), North Haven, CT, 2015.

13 ) Hohlfeld T , Saxena A , & Schror K : High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs--pharmacological mechanisms and clinical relevance. Thromb Haemost 2013; 109(5):825-833.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

14 ) Product Information: Sulindac oral tablets, sulindac oral tablets. Actavis Pharma Inc (per DailyMed)., Parsippany, NJ, 2019.

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.

Mefenamic Acid Overview

• Mefenamic acid is used to relieve mild to moderate pain, including menstrual pain (pain that happens before or during a menstrual period). Mefenamic acid is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.