Salsalate 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
Salsalate
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.
Salsalate is an anti-inflammatory pain reliever (an NSAID), and lisinopril is a blood pressure medicine. When you take them together, the salsalate can make the lisinopril work a little less well, so your blood pressure may not be controlled as tightly. The combination can also put extra stress on your kidneys, especially if you are older, dehydrated, or already have some kidney trouble.
The good news is this is very manageable. Your care team can check your blood pressure and run simple blood tests to keep an eye on your kidneys. 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: Salsalate (NSAID) may blunt the antihypertensive and natriuretic effect of lisinopril (ACE inhibitor) and, through additive effects on renal hemodynamics, may cause renal deterioration, including possible acute kidney injury.
Mechanism: NSAID inhibition of renal prostaglandin synthesis reduces afferent arteriolar vasodilation; combined with ACE inhibitor efferent effects, this compromises glomerular perfusion and blunts natriuresis. Neither agent is a prodrug affecting direction here.
Evidence/onset: Established; onset unspecified.
- Monitor BP for loss of efficacy
- Assess renal function at initiation and periodically (SCr, eGFR, K+)
- Higher risk: elderly, volume-depleted, preexisting CKD
- Ensure adequate hydration
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 blunted by NSAIDs. Using these agents together may also worsen renal function in certain patients, potentially causing acute renal failure. If the combination cannot be avoided, evaluate whether renal function should be tracked when therapy begins, watch for adequate antihypertensive response, and periodically check renal function for indications of decline or failure. This is particularly important in elderly patients, at the start of treatment, in individuals who are volume-depleted, and in those 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 blood pressure checks to make sure the lisinopril is still working.
- Expect periodic kidney blood tests, especially when you first start the combination.
- Stay well hydrated, which helps protect your kidneys.
- Tell your team if you are older, dehydrated, or have kidney problems, since you may need closer monitoring.
Report reduced urine output, swelling, or rising blood pressure to your pharmacist or prescriber.
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 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 bring the hypertension under control, and indomethacin was stopped. One day afterward, the patient underwent rapid diuresis with substantial weight loss. Enalapril was subsequently lowered back to 10 mg/day, achieving good hypertension control without any remaining psychosis 6.
b) In a randomized, double-blind, parallel-design multicenter study of 141 hypertensive patients, indomethacin opposed the antihypertensive action of captopril. One week of combined indomethacin and captopril therapy raised 24-hour systolic blood pressure 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. Over 5 weeks, blood pressure rose from 130 to 135/80 to 85 to 168/98. Rofecoxib was stopped. Blood pressure fell during the next 18 days (average, 127/78 mmHg). Because of increased joint pain, rofecoxib was resumed at 25 mg/day. Following 2 days of therapy, blood pressure rose, and it averaged 143/89 mmHg over the subsequent 2 weeks. Lisinopril was raised to 20 mg/day, yielding an average blood pressure of 121/81 mmHg during the next 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 regimen (10 to 40 mg daily), patients received 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 share 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 Salsalate and Lisinopril together?
Salsalate can weaken lisinopril's blood pressure control and stress the kidneys, so your care team should monitor your blood pressure and kidney function while you stay well hydrated. Don't stop either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Salsalate 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 Salsalate 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 blood pressure checks to make sure the lisinopril is still working. Expect periodic kidney blood tests, especially when you first start the combination. Stay well hydrated, which helps protect your kidneys. Tell your team if you… 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 Salsalate 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 Salsalate
Keep reading about Lisinopril
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