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Patients taking any of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs) should be aware that they all have clinically important interactions with many other medications.
NSAIDs are a large family of medications used to relieve pain, reduce fever and treat a variety of inflammatory disorders, such as osteoarthritis and rheumatoid arthritis. Table 1, below, provides a list of prescription and over-the-counter oral NSAIDs currently available in the U.S.
Among the best known...
Patients taking any of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs) should be aware that they all have clinically important interactions with many other medications.
NSAIDs are a large family of medications used to relieve pain, reduce fever and treat a variety of inflammatory disorders, such as osteoarthritis and rheumatoid arthritis. Table 1, below, provides a list of prescription and over-the-counter oral NSAIDs currently available in the U.S.
Among the best known and most frequently used NSAIDs are aspirin (BAYER ASPIRIN, DURLAZA, ECOTRIN, VAZALORE), ibuprofen (ADVIL, MIDOL LIQUID GELS, MOTRIN, TAB-PROFEN) and naproxen (ALEVE, ANAPROX DS, EC-NAPROSYN, NAPRELAN, NAPROSYN).
Table 1: List of Oral NSAIDs Currently Available in the U.S.
| Generic Name | Brand Name(s)† |
|---|---|
| aspirin | BAYER ASPIRIN, DURLAZA, ECOTRIN, VAZALORE |
| celecoxib* | CELEBREX, ELYXYB |
| diclofenac* | CAMBIA, CATAFLAM, ZIPSOR, ZORVOLEX |
| diflunisal* | generic only |
| etodolac** | generic only |
| fenoprofen** | NALFON |
| flurbiprofen | generic only |
| ibuprofen | ADVIL, MIDOL LIQUID GELS, MOTRIN, TAB-PROFEN |
| indomethacin* | INDOCIN |
| ketoprofen | generic only |
| ketorolac* | generic only |
| mefenamic acid** | PONSTEL |
| meloxicam* | MOBIC |
| nabumetone** | generic only |
| naproxen | ALEVE, ANAPROX DS, EC-NAPROSYN, NAPRELAN, NAPROSYN |
| piroxicam* | FELDENE |
| sulindac** | generic only |
†Combination brand-name drug products not listed
*Designated as Do Not Use by Worst Pills, Best Pills News
**Designated as Limited Use by Worst Pills, Best Pills News
Table 2: Examples of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
| Generic Name* | Brand Name(s)† |
|---|---|
| Angiotensin-Converting Enzyme Inhibitors | |
| benazepril | LOTENSIN |
| enalapril | EPANED, VASOTEC |
| lisinopril | PRINIVIL, QBRELIS, ZESTRIL |
| ramipril | ALTACE |
| Angiotensin Receptor Blockers | |
| candesartan | ATACAND |
| irbesartan | AVAPRO |
| losartan | COZAAR |
| valsartan | DIOVAN |
†Combination brand-name drug products not listed
*All listed examples are designated as Limited Use by Worst Pills, Best Pills News.
Drugs for hypertension[1]
Concomitant (at the same time) use of NSAIDs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) (see Table 2, above, for a list of examples) — which are commonly used to treat hypertension (high blood pressure) and heart failure — may result in acute kidney failure, particularly in patients who are elderly, dehydrated (from diuretic use, inadequate fluid intake or other circumstances) or have underlying kidney disease.[2] Therefore, patients using these drugs in combination need periodic blood tests to monitor kidney function.
Use of NSAIDs also may diminish the effectiveness of ACE inhibitors and ARBs in lowering blood pressure.
Increased risk of bleeding[3]
NSAIDs can cause inflammation, erosions and ulcers in the inner lining of the stomach and duodenum (the first part of the small intestine that is connected to the stomach), which can lead to bleeding. These drugs also inhibit the function of platelets, which play a key role in blood clotting.
Numerous oral drugs, when used concomitantly with NSAIDs, further increase the risk of bleeding. The list of such interacting drugs includes anticoagulants (blood thinners), antiplatelet drugs, glucocorticoids (also called corticosteroids), selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants (see Table 3, below, for a list of examples of each of these drug families).
Concomitant use of the dietary supplement ginkgo biloba with NSAIDS also may increase the risk of bleeding.
Table 3: Examples of Oral Drugs That Can Increase the Risk of Bleeding When Taken Concomitantly With NSAIDs
| Generic Name | Brand Name(s)† |
|---|---|
| Anticoagulants (Blood Thinners) | |
| apixaban* | ELIQUIS |
| edoxaban* | SAVAYSA |
| rivaroxaban* | XARELTO |
| warfarin | COUMADIN, JANTOVEN |
| Antiplatelet Drugs | |
| clopidogrel** | PLAVIX |
| prasugrel* | EFFIENT |
| ticagrelor | BRILINTA |
| ticlopidine* | generic only |
| Glucocorticoids | |
| dexamethasone | HEMADY |
| hydrocortisone | ALKINDI SPRINKLE, CORTEF |
| methylprednisolone | MEDROL |
| prednisone | RAYOS |
| Selective Serotonin Reuptake Inhibitors | |
| citalopram** | CELEXA |
| fluoxetine** | PROZAC |
| paroxetine** | PAXIL, PEXEVA |
| sertraline** | ZOLOFT |
| Serotonin-Norepinephrine Reuptake Inhibitors | |
| desvenlafaxine** | PRISTIQ |
| duloxetine* | CYMBALTA, DRIZALMA SPRINKLE |
| levomilnacipran** | FETZIMA |
| venlafaxine** | EFFEXOR XR |
| Tricyclic Antidepressants | |
| amitriptyline* | generic only |
| doxepin* | SILENOR |
| imipramine* | TOFRANIL |
| nortriptyline** | PAMELOR |
†Combination brand-name drug products not listed
*Designated as Do Not Use by Worst Pills, Best Pills News
**Designated as Limited Use by Worst Pills, Best Pills News
Other notable interactions[4]
Diuretics
Concomitant use of NSAIDs with any of the thiazide diuretics (water pills; for example, chlorthalidone [THALITONE] and hydrochlorothiazide [MICROZIDE]) or loop diuretics (for example, bumetanide [BUMEX] and furosemide [LASIX]) may result in decreased effectiveness of the diuretic and possible kidney injury.
Concomitant use of NSAIDs with any of the potassium-sparing diuretics, such as spironolactone (ALDACTONE) and triamterene (DYRENIUM), may cause reduced diuretic effectiveness, possible kidney injury and hyperkalemia (high blood potassium levels).
Lithium
Concomitant use of NSAIDS with lithium (LITHOBID), a mood-stabilizing drug used to treat bipolar disorder, may cause blood lithium to increase to toxic levels. Nausea, diarrhea, vomiting, loss of appetite, drowsiness, muscle weakness and decreased coordination are early signs of lithium toxicity. With increasing blood lithium levels, patients can experience giddiness, ataxia (severe lack of muscle control or coordination of voluntary movements), slurred speech, blurred vision, tinnitus (perception of noise or ringing in the ears) and markedly increased urine output. Severe lithium toxicity can lead to seizures, coma, abnormal heart rhythms and even death.
What You Can Do
If you need treatment with an NSAID, review all of your other medications with your doctor to assess for potentially significant drug interactions. If you are taking certain medications that interact with NSAIDs, you may need to adjust the dosage of the interacting drug or undergo more frequent monitoring of the blood levels of the interacting drug or of your kidney function and blood potassium levels, or your doctor may advise you to take a different drug. Be aware that other drugs not listed in this article also may have dangerous interactions with NSAIDs.
References
[1] Ibid.
[2] Atnahs Pharma. Label: naproxen (NAPROSYN). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/017581s115,018164s065,020067s064lbl.pdf. Accessed March 7, 2022.
[3] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “ibuprofen.” Accessed March 7, 2022.
[4] Ibid.
