Epinephrine and Penbutolol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Penbutolol
Epinephrine
No brand names on record
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.
What happens
Antagonized cardio stimulating, bronchodilation effects of EPINEPHrine and an increased risk of hypertension
Interaction Deep Dive
Avoid concomitant use of local anesthetics containing EPINEPHrine and nonselective beta-adrenergic antagonists, such as penbutolol, as severe, prolonged hypertension may occur. If concurrent therapy is necessary, carefully monitor patient for severe and prolonged hypertension1. Concomitant use of EPINEPHrine and penbutolol may antagonize the cardiostimulating and bronchodilating effects of EPINEPHrine 2.
Why it happens (mechanism)
Unknown; additive vasoconstricting effects
Literature reports
4 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.
Common questions
Can I take Epinephrine and Penbutolol together?
Antagonized cardio stimulating, bronchodilation effects of EPINEPHrine and an increased risk of hypertension Always confirm with your pharmacist or prescriber before making any change.
How serious is the Epinephrine and Penbutolol interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Epinephrine or Penbutolol 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 (8)
- Product Information: Septocaine(R) injection, articaine HCl epinephrine injection. Septodont (per FDA), Louisville, CO, 2018. DailyMed
- Product Information: NEFFY(R) nasal spray, epinephrine nasal spray. ARS Pharmaceuticals Operations, Inc. (per FDA), San Diego, CA, 2024. DailyMed
- Newman BR & Schultz LK: Epinephrine-resistant anaphylaxis in a patient taking propranolol hydrochloride. Ann Allergy 1981; 47:35-37.
- Pollack CV Jr: Utility of glucagon in the emergency department. J Emerg Med 1993; 11:195-205. PubMed
- 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.
- Kram J, Bourne HR, Melmon KL, et al: Propranolol (letter). Ann Intern Med 1974; 80:282.
- Foster CA & Aston SJ: Propranolol-epinephrine interaction: a potential disaster. Plast Reconstr Surg 1983; 72:74-78. PubMed
- Varma DR, Shama KK, & Arora RC: Response to adrenalin and propranolol in hyperthyroidism. Lancet 1976; 1:260.
Keep reading about Penbutolol
Keep reading about Epinephrine
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