Diflunisal and Lisinopril: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diflunisal
Lisinopril
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Diflunisal (Dolobid) is an anti-inflammatory pain reliever (an NSAID), and lisinopril (Zestril, Prinivil) is a blood pressure medicine. When you take them together, the diflunisal can make the lisinopril work less well, so your blood pressure may not be controlled as nicely. Both drugs can also put extra stress on your kidneys, which matters more if you are older, dehydrated, or already have kidney trouble.
The good news is your care team can manage this easily. They may check your blood pressure and run kidney (blood) tests now and then, and staying well hydrated helps. Don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Diflunisal (NSAID) may blunt the antihypertensive and natriuretic effect of lisinopril (ACE inhibitor) and increase risk of renal deterioration, including acute kidney injury.
Mechanism: NSAID inhibition of renal prostaglandin synthesis reduces afferent arteriolar vasodilation; combined with ACEi efferent effects, this compromises glomerular perfusion, plus additive renal effects. Neither is a prodrug.
- Direction: reduced lisinopril efficacy; increased renal risk
- Evidence: established; onset unspecified
- Management: monitor BP for efficacy; assess renal function (SCr, eGFR) at initiation and periodically; maintain hydration. Higher risk in elderly, volume-depleted, or preexisting renal impairment.
What happens
Reduced antihypertensive effect and renal dysfunction and/or increased blood pressure
Interaction Deep Dive
The natriuretic and blood pressure lowering actions of ACE inhibitors or angiotensin receptor blockers (ARBs) can be reduced by NSAIDs. Combining these agents may also cause worsening of renal function in certain patients, up to and including acute renal failure. If the two must be given together, evaluate whether renal function monitoring is warranted when therapy begins, watch for adequate antihypertensive response, and check renal function at intervals for evidence of declining function or failure, particularly in elderly patients, at the start of treatment, in those who are volume-depleted, or in individuals with existing renal impairment. Confirm that patients maintain adequate hydration1234.
Why it happens (mechanism)
Additive effects on renal function; decreased renal prostaglandin production
How to manage this interaction
This combination can be used when needed, but your care team will keep an eye on things:
- Blood pressure checks to make sure your lisinopril is still working well.
- Kidney blood tests at the start and from time to time, especially if you are older, low on fluids, or have kidney issues.
- Stay well hydrated unless told otherwise.
Keep taking both exactly as prescribed. Your dose may be adjusted and individualized by your care team if needed. Tell your pharmacist or doctor about swelling, much less urine, rising blood pressure, or feeling unwell.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A 48-year-old man with hypertension that had previously been well managed on enalapril 10 mg/day developed severe hypertension, psychosis, disorientation, and generalized anasarca four days after starting indomethacin 100 mg/day for gout 5. Raising the enalapril dose to 20 mg/day did not control the hypertension, and indomethacin was stopped. The following day, the patient underwent rapid diuresis with substantial weight loss. The enalapril dose was subsequently lowered back to 10 mg/day, achieving good blood pressure control with no lingering psychosis 6.
b) In a randomized, double-blind, parallel-design multicenter study of 141 hypertensive patients, indomethacin opposed the antihypertensive action of captopril. After one week of taking indomethacin and captopril together, 24-hour systolic blood pressure rose by 4.6 mmHg and diastolic by 2.7 mmHg (p less than 0.001). In total, ambulatory diastolic blood pressure increased in 67% of the patients receiving captopril while on indomethacin 7.
c) A 59-year-old man who had been treated with lisinopril 10 mg/day for 5 years experienced worsening hypertension after rofecoxib 25/day was started for arthritic pain. At 5 weeks, blood pressure had risen from 130 to 135/80 to 85 up to 168/98. Rofecoxib was stopped, and blood pressure fell over the subsequent 18 days (averaging 127/78 mmHg). Because of increased joint pain, rofecoxib was resumed at 25 mg/day. Two days into this therapy, blood pressure climbed, and over the next 2 weeks it averaged 143/89 mmHg. Lisinopril was raised to 20 mg/day, which produced an average blood pressure of 121/81 mmHg across the following 21 days 8.
d) In a double-blind, placebo-controlled, parallel-group trial of 178 hypertensive patients, celecoxib did not diminish the antihypertensive effect of lisinopril. Patients received either celecoxib 200 mg twice daily or placebo added to their usual lisinopril regimen (10 to 40 mg daily) for 4 weeks. Changes from baseline in 24-hour systolic and diastolic blood pressure (BP) were nonsignificant. The proportion of patients whose 24-hour BP rose by at least 5, 10, 15, or 20 mmHg was likewise comparable between celecoxib and placebo. The placebo-subtracted changes seen in 24-hour BP (1.6/1.2 mmHg) were smaller than those reported for NSAIDs in patients treated with ACE inhibitors 9.
Common questions
Can I take Diflunisal and Lisinopril together?
Diflunisal can weaken lisinopril's blood pressure effect and stress the kidneys, so your team may monitor your blood pressure and kidney function and keep you hydrated. Keep taking both as prescribed unless your doctor or pharmacist advises otherwise. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diflunisal and Lisinopril interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Diflunisal and Lisinopril interaction managed?
This combination can be used when needed, but your care team will keep an eye on things: Blood pressure checks to make sure your lisinopril is still working well. Kidney blood tests at the start and from time to time, especially if you are older, low on fluids, or have kidney issues. Stay well hydrated unless told otherwise. Keep taking both exactly as prescribed. Your dose may be adjusted and ind… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Diflunisal or Lisinopril need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (9)
- Product Information: Dynastat intravenous injection, intramuscular injection, parecoxib sodium intravenous injection, intramuscular injection. Pfizer Australia Pty Ltd (per Australian Register of Therapeutic Goods), West Ryde, Australia, 2017. DailyMed
- Product Information: SPRIX(R) nasal spray, ketorolac tromethamine nasal spray. Egalet US Inc. (per FDA), Wayne, PA, 2016. DailyMed
- Product Information: CALDOLOR(R) intravenous injection, ibuprofen intravenous injection. Cumberland Pharmaceuticals Inc. (per FDA), Nashville, TN, 2016. DailyMed
- Product Information: meloxicam oral tablets, meloxicam oral tablets. Apotex Corp. (per DailyMed), Weston, FL, 2016. DailyMed
- Ahmad S: Indomethacin-enalapril interaction: an alert (letter). South Med J 1991; 84:411-412. PubMed
- Morgan T, Anderson A, & Bertram D: Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. Am J Hypertens 2000; 13:1161-1167. PubMed
- Conlin P, Moore T, Swartz S, et al: Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients. Hypertension 2000; 36:461-465. PubMed
- Brown C: Effect of rofecoxib on the antihypertensive activity of lisinopril (letter). Ann Pharmacother 2000; 34:1486. PubMed
- White W, Kent J, Taylor A, et al: Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors. Hypertension 2002; 39:929-934. PubMed
Keep reading about Diflunisal
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