Tolfenamic Acid 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
Lisinopril
Tolfenamic Acid
No brand names on record
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.
Lisinopril is a blood pressure medicine, and tolfenamic acid is an anti-inflammatory painkiller (an NSAID). When taken together, the NSAID can make lisinopril work less well, so your blood pressure may creep back up. These two can also be a little hard on your kidneys, especially if you are older, dehydrated, or already have kidney trouble.
This does not mean you can't take both. It just means your care team may want to check your blood pressure and do a simple kidney blood test now and then. Staying well hydrated helps too. Please don't stop either medicine on your own, just talk with your pharmacist or doctor about the best plan for you.
Effect: NSAIDs such as tolfenamic acid reduce the antihypertensive and natriuretic response to ACE inhibitors like lisinopril, and the combination increases risk of renal deterioration, including acute renal failure.
Mechanism: NSAID inhibition of renal prostaglandin synthesis reduces afferent arteriolar vasodilation; combined with ACE-inhibitor efferent vasodilation, this compromises glomerular perfusion (additive renal effect). Neither agent is affected by CYP-based prodrug activation here.
Evidence: Established. Onset: unspecified. Management:
- Monitor renal function at initiation and periodically
- Monitor BP for loss of antihypertensive efficacy
- Ensure adequate hydration
- Heightened vigilance in elderly, volume-depleted, or preexisting renal dysfunction
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. Furthermore, giving these agents together may worsen renal function in certain patients, potentially causing acute renal failure. If the combination cannot be avoided, evaluate whether renal function monitoring is warranted when therapy begins, watch for adequate antihypertensive response, and periodically check renal function for indications of declining kidney function or failure. This is particularly important in elderly patients, at the start of treatment, in those who are volume-depleted, and 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
If your care team decides you need both medicines, they can manage this safely.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Expect your team to check your kidney function with a blood test when you start and from time to time.
- Expect them to watch your blood pressure to make sure the lisinopril is still working well.
- Stay well hydrated, especially if you are unwell, vomiting, or have diarrhea.
Tell your pharmacist or doctor if you notice much higher blood pressure, less urine, swelling, or unusual tiredness. Extra care is wise if you are older or already have kidney issues.
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 been well-controlled with enalapril 10 mg/day developed severe hypertension, psychosis, disorientation, and generalized anasarca four days after beginning indomethacin 100 mg/day for gout 5. Raising the enalapril dose to 20 mg/day did not control the hypertension, so indomethacin was stopped. Within one day, the patient underwent rapid diuresis and lost a substantial amount of weight. 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 counteracted the antihypertensive action of captopril. After one week of taking indomethacin together with captopril, 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 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. After 5 weeks, his blood pressure rose from 130 to 135/80 to 85 to 168/98. Rofecoxib was stopped. Over the following 18 days, his blood pressure fell (averaging 127/78 mmHg). Because of increased joint pain, rofecoxib was resumed at 25 mg/day. Two days into this therapy, blood pressure rose, and over the next 2 weeks it averaged 143/89 mmHg. Lisinopril was raised to 20 mg/day, producing an average blood pressure of 121/81 mmHg over 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. In addition to their usual lisinopril therapy (10 to 40 mg daily), patients received either celecoxib 200 mg twice daily or placebo for 4 weeks. Changes from baseline in 24-hour systolic and diastolic blood pressure (BP) were nonsignificant. The proportions of patients whose 24-hour BP rose by at least 5, 10, 15, or 20 mmHg were also comparable between celecoxib and placebo. The placebo-subtracted changes seen in 24-hour BP (1.6/1.2 mmHg) were smaller than what has been reported for NSAIDs in patients treated with ACE inhibitors 9.
Common questions
Can I take Tolfenamic Acid and Lisinopril together?
Tolfenamic acid can blunt lisinopril's blood pressure effect and strain the kidneys, so keep taking both as prescribed while your care team monitors your blood pressure and kidney function and you stay well hydrated. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tolfenamic Acid 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 Tolfenamic Acid and Lisinopril interaction managed?
If your care team decides you need both medicines, they can manage this safely. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Expect your team to check your kidney function with a blood test when you start and from time to time. Expect them to watch your blood pressure to make sure the lisinopril is still working well. Stay well hydrated, especially if you ar… 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 Tolfenamic Acid 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 Lisinopril
Keep reading about Tolfenamic Acid
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