Drug Interaction Report

Esmolol and Epinephrine: Interaction Details

A pharmacist-reviewed analysis of the Esmolol and Epinephrine interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Epinephrine

No brand names on record
+

Esmolol

Brevibloc
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 191 documented Esmolol interactions, 36 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

An increased risk of cardiac arrhythmias, an antagonized cardio stimulating and bronchodilation effects of EPINEPHrine, an increased risk of severe hypertension and an increased risk of bradycardia

Interaction Deep Dive

Avoid coadministration of EPINEPHrine with beta-blocker and antiarrhythmic agents as it may cause severe hypertension and bradycardia with possible heart block. In situations when concurrent therapy is necessary, careful monitor patient’s blood pressure and heart rate1. EPINEPHrine may precipitate or aggravate angina pectoris, as well as produce ventricular arrhythmias. If concomitant use is required, observe patients carefully for the development of cardiac arrhythmias 2.

Why it happens (mechanism)

Unknown

Literature reports

5 reports — tap to read

a) Following inhalation therapy with EPINEPHrine, concurrent propranolol administration may inhibit EPINEPHrine-induced bronchodilatation (mediated through beta-2 receptors) and increase the patient's blood pressure (due to unopposed alpha stimulation), especially if the EPINEPHrine dose is repeated. EPINEPHrine failed to reverse an anaphylactic reaction to a maintenance allergy injection in a patient on chronic oral propranolol. Intubation, neuromuscular blockade, antihistamine, and steroids were used during supportive care 3. Cardioselective beta blockers (atenolol, metoprolol, acebutolol), however, appear to have little effect on the pressor response to EPINEPHrine and low doses are not likely to interfere with EPINEPHrine-induced bronchodilatation. The effect of larger doses on bronchodilatation produced by EPINEPHrine is not well studied at this time 4.

b) Acute hypertension followed by a reflex bradycardia can occur during combined propranolol (or other nonselective beta-blockers) and EPINEPHrine therapy 56. The hypertensive effect is related to blocking of beta-receptors resulting in alpha-receptor dominance and a paradoxical hypertension. Bradycardia represents a secondary reflex cardiac response mediated by vagally-innervated aortic arch and carotid baroreceptors. Propranolol results in this latter effect by inhibiting the ability of the cardiovascular system to respond appropriately to this added stress. Elevated peripheral resistance increases the work load of the myocardium, and it is unable to be stimulated to increase its output, thus resulting in reflex bradycardia. This sequence of events may result in cardiac arrest or hypertensive stroke 76.

c) Propranolol pretreatment followed by EPINEPHrine infusion was reported to lower the pulse rate to 30 beats per minute with first- and second-degree AV block in a healthy 22-year-old male 6. In 4 hypertensive patients and 5 normal subjects, EPINEPHrine alone (0.4 mg subcutaneously) produced an increase in heart rate and minimal effects on blood pressure; but with propranolol pretreatment (40 mg orally), EPINEPHrine produced a 20 to 40 mmHg rise in blood pressure and a 23 to 26 beats per minute decrease in heart rate 8.

d) An interaction was demonstrated in a hemodynamic study evaluating the effect of low-dose EPINEPHrine (in an attempt to simulate situations of daily life stress) on patients receiving either propranolol or metoprolol. EPINEPHrine was infused at graded rates of 0.5, 1, 2, and 4 mcg/min, with each dose sustained for 8 minutes. While the hypertensive patients were maintained on propranolol 80 mg/day, low-dose EPINEPHrine infusion caused a marked rise in systolic as well as diastolic blood pressure and decreases in heart rate. However, when patients were maintained on metoprolol 100 mg daily, EPINEPHrine infusion induced only a slight rise in blood pressure and an increase in heart rate. The effect of EPINEPHrine may have relevance in the choice of which beta-blocker should be used for the treatment of hypertension. Metoprolol, because it is selective for beta-1 receptor blockade, appears to be a better choice than propranolol in the treatment of hypertension 5.

e) Nonselective beta blockers such as carvedilol may also cause resistance to EPINEPHrine in cases of anaphylaxis 39. Nonselective beta blockers when used concurrently with EPINEPHrine result in a hypertensive response to EPINEPHrine and a reflex bradycardia. This is well-documented with propranolol and is expected to also occur with carvedilol. Nonselective beta blockers block the beta effects of EPINEPHrine, resulting in unopposed alpha effects 1011. Other nonselective beta blockers such as labetalol are expected to have the same effect, although labetalol appears to have less impact than propranolol on blocking the vasodepressor and chronotropic effects of EPINEPHrine 12.

Common questions

Can I take Esmolol and Epinephrine together?

An increased risk of cardiac arrhythmias, an antagonized cardio stimulating and bronchodilation effects of EPINEPHrine, an increased risk of severe hypertension and an increased risk of bradycardia Always confirm with your pharmacist or prescriber before making any change.

How serious is the Esmolol and Epinephrine interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

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 Esmolol or Epinephrine 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 a safer alternative to one of these medications for me?

References (12)

  1. Product Information: FLAVALTA injection solution, lidocaine hydrochloride and epinephrine injection solution. SEPTODONT Inc. Lancaster, PA, 2026. DailyMed
  2. Product Information: NEFFY(R) nasal spray, epinephrine nasal spray. ARS Pharmaceuticals Operations, Inc. (per FDA), San Diego, CA, 2024. DailyMed
  3. Newman BR & Schultz LK: Epinephrine-resistant anaphylaxis in a patient taking propranolol hydrochloride. Ann Allergy 1981; 47:35-37.
  4. Pollack CV Jr: Utility of glucagon in the emergency department. J Emerg Med 1993; 11:195-205. PubMed
  5. Houben H, Thien T, & van't Laar A: Effect of low dose epinephrine infusion on hemodynamics after selective and nonselective beta-blockade in hypertension. Clin Pharmacol Ther 1982; 31:685-690.
  6. Kram J, Bourne HR, Melmon KL, et al: Propranolol (letter). Ann Intern Med 1974; 80:282.
  7. Foster CA & Aston SJ: Propranolol-epinephrine interaction: a potential disaster. Plast Reconstr Surg 1983; 72:74-78. PubMed
  8. Varma DR, Shama KK, & Arora RC: Response to adrenalin and propranolol in hyperthyroidism. Lancet 1976; 1:260.
  9. Awai LE & Mekori YA: Insect sting anaphylaxis and beta-adrenergic blockade: a relative contraindication. Ann Allergy 1984; 53:48-49.
  10. Gandy W: Severe epinephrine-propranolol interaction. Ann Emerg Med 1989; 18:98-99.
  11. van Herwaarden CL, Binkhorst RA, Fennis JF, et al: Effects of adrenaline during treatment with propranolol and metoprolol (letter). Br Med J 1977; 1:1029. PubMed
  12. Doshi BS, Kulkarni RD, Dattani KK, et al: Effects of labetalol and propranolol on responses to adrenaline infusion in healthy volunteers. Int J Clin Pharm Res 1984; 4:29-33.
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Beyond drug–drug

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:

Epinephrine + Activated Charcoal Butcher's Broom Coffee Charcoal European Mandrake Glucomannan Guar Gum Gum Arabic Slippery Elm + 10 more
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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.