Phenylbutazone 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
Phenylbutazone
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 phenylbutazone is an anti-inflammatory pain reliever (an NSAID). When taken together, the NSAID can make your blood pressure medicine work less well, so your blood pressure may creep up. Just as important, the combination can put extra stress on your kidneys, especially if you are older, dehydrated, or already have kidney trouble.
The good news is your care team can manage this. They may check your kidney function and keep an eye on your blood pressure. Keep taking both as prescribed, stay well hydrated, and talk with your pharmacist or doctor before making any changes.
Effect: NSAID (phenylbutazone) blunts the antihypertensive and natriuretic effect of the ACE inhibitor lisinopril, with additive risk of renal deterioration, including possible acute kidney injury.
Mechanism: Inhibition of renal prostaglandin synthesis reduces afferent arteriolar vasodilation; combined with ACE-inhibitor efferent effects, this compromises glomerular perfusion. Neither agent is a prodrug in this context.
- Direction: reduced antihypertensive efficacy; increased nephrotoxicity risk
- Onset: unspecified; Evidence: established; Severity: moderate
- Monitor: BP, renal function/SCr at initiation and periodically; ensure adequate hydration
- Highest risk: elderly, volume-depleted, preexisting renal dysfunction
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) can be blunted by NSAIDs. Using these agents together may also cause worsening renal function in certain patients, up to and including acute renal failure. If simultaneous use cannot be avoided, evaluate whether renal function should be checked when therapy begins, watch for adequate blood pressure control, and periodically assess renal function to detect any decline or failure, particularly in elderly patients, at the start of treatment, in those who are volume-depleted, or in individuals with preexisting 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 you need both medicines, your care team has clear ways to keep you safe:
- They may check your kidney function when starting and then periodically.
- They will watch your blood pressure to be sure the lisinopril is still working well.
- Your doses may need to be adjusted and individualized by your care team.
What you can do:
- Keep taking both as prescribed unless told otherwise.
- Stay well hydrated.
- Tell your pharmacist or doctor if you notice less urine, swelling, unusual tiredness, or rising blood pressure readings, especially if you are older or 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 previously been well-controlled 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 failed to control his hypertension, so indomethacin was stopped. One day afterward, 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 hypertension control with no lingering psychosis 6.
b) In a randomized, double-blind, parallel-design multicenter study of 141 hypertensive patients, indomethacin counteracted the blood pressure lowering effect of captopril. Taking indomethacin and captopril together for one week raised 24-hour systolic blood pressure by 4.6 mmHg and diastolic blood pressure by 2.7 mmHg (p less than 0.001). Across the group, 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, his 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 on this therapy, blood pressure rose, and over the subsequent 2 weeks it averaged 143/89 mmHg. Lisinopril was raised to 20 mg/day, which produced an average blood pressure of 121/81 mmHg over the following 21 days 8.
d) In a double-blind, placebo-controlled, parallel-group trial involving 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. The changes from baseline in 24-hour systolic and diastolic blood pressure (BP) were not significant. The proportions of patients whose 24-hour BP rose by at least 5, 10, 15, or 20 mmHg were 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 Phenylbutazone and Lisinopril together?
Phenylbutazone can weaken lisinopril's blood pressure control and stress the kidneys, so keep taking both as prescribed while your care team monitors your blood pressure and kidney function and keeps you well hydrated. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenylbutazone 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 Phenylbutazone and Lisinopril interaction managed?
If you need both medicines, your care team has clear ways to keep you safe: They may check your kidney function when starting and then periodically. They will watch your blood pressure to be sure the lisinopril is still working well. Your doses may need to be adjusted and individualized by your care team. What you can do: Keep taking both as prescribed unless told otherwise. Stay well hydrated. Te… 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 Phenylbutazone 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 Phenylbutazone
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist