Lisinopril and Nepafenac: 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
Nepafenac
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 lowers your blood pressure and helps protect your kidneys. Nepafenac is an anti-inflammatory (an NSAID) that comes as an eye drop, but even eye drops can be absorbed into the body a little. NSAIDs can work against lisinopril by making it a bit less effective at lowering blood pressure, and together they can put extra stress on the kidneys.
This matters most if you are older, dehydrated, or already have kidney trouble. The good news is this is very manageable. Keep using both as prescribed, stay well hydrated, and let your care team know you use both so they can check your blood pressure and kidneys as needed.
Effect: NSAIDs (including nepafenac) can reduce the antihypertensive and natriuretic effect of ACE inhibitors and may worsen renal function via additive effects and decreased renal prostaglandin synthesis, reducing afferent arteriolar perfusion.
- Direction: reduced lisinopril efficacy; increased risk of renal deterioration, including acute renal failure.
- Evidence: established; onset unspecified. Note nepafenac is topical ophthalmic, so systemic exposure is generally low.
- Management: assess baseline renal function, monitor for antihypertensive efficacy and BP control, reassess renal function periodically. Ensure adequate hydration.
- Higher risk: elderly, volume-depleted, preexisting renal dysfunction, treatment initiation.
What happens
Reduced antihypertensive effect and renal dysfunction and/or increased blood pressure
Interaction Deep Dive
The antihypertensive and natriuretic actions of ACE inhibitors or angiotensin receptor blockers (ARBs) may be reduced by NSAIDs. Furthermore, giving these drugs together can lead to worsening renal function in some patients, up to and including acute renal failure. If the two must be used together, evaluate whether renal function should be checked when therapy begins, watch for adequate blood pressure control, and periodically assess renal function to detect any deterioration 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 are sufficiently hydrated1234.
Why it happens (mechanism)
Additive effects on renal function; decreased renal prostaglandin production
How to manage this interaction
Your care team can manage this easily by keeping an eye on how well things are working.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Stay well hydrated, which helps protect your kidneys.
- Your team may check your blood pressure to make sure the lisinopril is still controlling it.
- They may also check your kidney function, especially when you first start, if you are older, or if you already have kidney problems.
Tell your pharmacist or prescriber if you notice much less urine, swelling, or unusually high blood pressure readings.
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, previously 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, so indomethacin was stopped. One day afterward, the patient underwent rapid diuresis and lost a considerable amount of weight. The enalapril dose was subsequently lowered to 10 mg/day, achieving good blood pressure control with no lasting psychosis 6.
b) In a randomized, double-blind, parallel-design multicenter study of 141 hypertensive patients, indomethacin opposed the blood pressure lowering effect 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. Following 5 weeks, blood pressure rose from 130 to 135/80 to 85 to 168/98. Rofecoxib was stopped. Blood pressure fell over the next 18 days (average, 127/78 mmHg). Because of increased joint pain, rofecoxib was resumed at 25 mg/day. After 2 days of treatment, blood pressure increased, and over the subsequent 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. Patients received either celecoxib 200 mg twice daily or placebo in addition to their usual lisinopril therapy (10 to 40 mg daily) for 4 weeks. The 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 also 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 Lisinopril and Nepafenac together?
Nepafenac can slightly weaken lisinopril's blood pressure effect and add strain on the kidneys, so keep taking both as prescribed, stay hydrated, and let your care team monitor your blood pressure and kidney function. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Nepafenac 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 Lisinopril and Nepafenac interaction managed?
Your care team can manage this easily by keeping an eye on how well things are working. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Stay well hydrated, which helps protect your kidneys. Your team may check your blood pressure to make sure the lisinopril is still controlling it. They may also check your kidney function, especially when you first start, if yo… 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 Lisinopril or Nepafenac 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 Nepafenac
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