Atenolol and Phenylbutazone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 15, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Atenolol
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.
You're taking atenolol to help control your blood pressure, and phenylbutazone is an anti-inflammatory (an NSAID). When these two are used together, the NSAID can make your blood pressure medicine work a little less well, so your blood pressure may not stay as low as your doctor wants. This happens because NSAIDs affect substances in your kidneys that help control blood pressure and fluid.
The good news is this is very manageable. Please keep taking both exactly as prescribed, and let your care team know you're on both. They may simply check your blood pressure a bit more closely and adjust your treatment if needed.
Effect: Reduced antihypertensive efficacy of atenolol when combined with phenylbutazone (an NSAID).
Mechanism: NSAID-mediated inhibition of renal prostaglandin synthesis, promoting sodium/fluid retention and blunting beta-blocker BP control. This is a PD interaction; neither agent's clearance drives it.
- Direction: Decreased effect of atenolol (higher BP).
- Onset: Delayed.
- Evidence: Probable (documented for several NSAIDs; sulindac may spare this effect).
- Magnitude: Variable, often modest but clinically relevant.
Management: Monitor blood pressure during concurrent use; individualize antihypertensive dosing as needed.
What happens
Reduced antihypertensive effect
Interaction Deep Dive
Taking NSAIDs together with beta-adrenergic blockers can raise blood pressure and undermine blood pressure management94. Such an effect has been noted with flurbiprofen (400 mg daily), ibuprofen (above 400 mg daily), indomethacin (above 50 mg daily), naproxen (1000 mg daily), and piroxicam6510. In contrast, sulindac may not counteract the antihypertensive action of beta-blockers1110. When NSAIDs and beta blockers must be used together, blood pressure should be monitored14.
Why it happens (mechanism)
Decreased production of renal prostaglandins
How to manage this interaction
This interaction is usually well controlled with monitoring, so keep taking both medications as prescribed unless your care team tells you otherwise.
- Your team may check your blood pressure more closely while you're on both drugs.
- If your blood pressure rises, your antihypertensive dose may need to be adjusted and individualized by your care team.
- Tell your pharmacist or prescriber if you notice higher home blood pressure readings, headaches, or swelling.
- Ask before starting any new over-the-counter pain relievers, since many are NSAIDs.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Hypertensive patients maintained on their customary medications received ibuprofen 400 mg orally every 8 hours, acetaminophen, or placebo. After the 3-week study concluded, those receiving ibuprofen exhibited rises of about 6 mmHg across the various blood pressure measurements. Acetaminophen produced no observable effect on blood pressure. The proposed mechanism may involve a lessening of the effectiveness of antihypertensive drugs due to interference with the generation of vasodilator and natriuretic prostaglandins that antihypertensive agents stimulate. A decrease in sodium excretion may have contributed to worsening the hypertension 5.
b) The influence of naproxen and sulindac on blood pressure response was investigated in 28 patients with mild to moderate essential hypertension that was well controlled by atenolol. Findings from this 5-week, double-blind, placebo-controlled trial showed that 1 week of naproxen 500 mg twice daily significantly raised systolic blood pressure (mean 4 mmHg) but produced no change in diastolic blood pressure. Sulindac 200 mg twice daily for 1 week did not modify either blood pressure measure 6.
c) The effects of indomethacin were assessed in 16 patients with essential hypertension who were treated with oxprenolol. Indomethacin and oxprenolol individually, as well as the two drugs together, suppressed plasma renin activity. When both drugs were administered in combination, blood pressure fell (systolic: -5.9 mmHg; diastolic: -4 mmHg; mean: -4.6 mmHg), but the blood pressure changes produced were diminished by approximately 50% relative to those observed during the period with oxprenolol alone 7.
d) Simultaneous administration of oral naproxen 500 mg twice daily or oral sulindac 200 mg twice daily produced no effect on blood pressure control in patients with mild to moderate hypertension managed with oral propranolol 10 mg to 240 mg daily in a single-blind study. Serum propranolol levels were not measured, and patients with existing renal disease, heart failure, or cirrhosis were not included 8.
Common questions
Can I take Atenolol and Phenylbutazone together?
Phenylbutazone can make atenolol work less well at lowering blood pressure, so your care team may monitor your blood pressure more closely and adjust treatment if needed. Keep taking both as prescribed and report any high readings. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Atenolol and Phenylbutazone interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Atenolol and Phenylbutazone interaction managed?
This interaction is usually well controlled with monitoring, so keep taking both medications as prescribed unless your care team tells you otherwise. Your team may check your blood pressure more closely while you're on both drugs. If your blood pressure rises, your antihypertensive dose may need to be adjusted and individualized by your care team. Tell your pharmacist or prescriber if you notice h… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Atenolol or Phenylbutazone 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 (11)
- Product Information: ZORVOLEX(R) oral capsules, diclofenac oral capsules. Iroko Pharmaceuticals, LLC (per FDA), Philadelphia, PA, 2016. DailyMed
- Product Information: ANAPROX(R) DS oral tablets, naproxen sodium oral tablets. Canton Laboratories, LLC (per FDA), Alpharetta, GA, 2016. DailyMed
- Product Information: CALDOLOR(R) intravenous injection, ibuprofen intravenous injection. Cumberland Pharmaceuticals Inc. (per FDA), Nashville, TN, 2016. DailyMed
- Product Information: COMBOGESIC(R) oral tablets, acetaminophen ibuprofen oral tablets. AFT Pharmaceuticals Inc (per FDA), Highland, MD, 2023. DailyMed
- Radack KL, Deck CC, & Bloomfield SS: Ibuprofen interferes with the efficacy of antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen. Ann Intern Med 1987; 107:628-635. PubMed
- Abate MA, Layne RD, Neely JL, et al: Effect of naproxen and sulindac on blood pressure response to atenolol. Drug Intell Clin Pharm 1990; 24:810-813. DOI
- Salvetti A, Arzilli F, Pedrinelli R, et al: Interaction between oxprenolol and indomethacin on blood pressure in essential hypertensive patients. Eur J Clin Pharmacol 1982; 22:197-201. DOI
- Schuna AA, Vejraska BD, Hiatt JG, et al: Lack of interaction between sulindac or naproxen and propranolol in hypertensive patients. J Clin Pharmacol 1989; 29:524-528. PubMed
- Product Information: VIMOVO(TM) delayed release oral tablets, naproxen and esomeprazole magnesium delayed release oral tablets. AstraZeneca LPW, Wilmington, DE, 2010. DailyMed
- Salvetti A, Pedrinelli R, Alberici P, et al: The influence of indomethacin and sulindac on some pharmacological actions of atenolol in hypertensive patients. Br J Clin Pharmacol 1984; 17(suppl):108S-111S. PubMed
- Abate MA, Neely JL, Layne RD, et al: Interaction of indomethacin and sulindac with labetolol. Br J Clin Pharmacol 1991; 31:363-366.
Keep reading about Atenolol
Keep reading about Phenylbutazone
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