Skip to Content

EpiPen Side Effects

Generic Name: epinephrine

Note: This page contains information about the side effects of epinephrine. Some of the dosage forms included on this document may not apply to the brand name EpiPen.

For the Consumer

Applies to epinephrine: injection injectable, injection solution

In addition to its needed effects, some unwanted effects may be caused by epinephrine (the active ingredient contained in EpiPen). In the event that any of these side effects do occur, they may require medical attention.

Severity: Major

You should check with your doctor immediately if any of these side effects occur when taking epinephrine:

Incidence not known:
  • Abnormal or decreased touch sensation
  • arm, back, or jaw pain
  • bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
  • blurred vision
  • chest pain or discomfort
  • chest tightness or heaviness
  • dizziness
  • fainting
  • fast, irregular, pounding, or racing heartbeat or pulse
  • fear or nervousness
  • headache
  • nausea or vomiting
  • paleness of the skin
  • pounding in the ears
  • restlessness
  • shakiness in the legs, arms, hands, or feet
  • slow or fast heartbeat
  • stroke
  • sweating
  • trembling or shaking of the hands or feet
  • troubled breathing
  • unusual tiredness or weakness

If any of the following symptoms of overdose occur while taking epinephrine, get emergency help immediately:

Symptoms of overdose:
  • Agitation
  • coldness of the skin
  • coma
  • confusion
  • decreased urine output
  • depression
  • drowsiness
  • hostility
  • irritability
  • lethargy
  • lightheadedness, dizziness, or fainting
  • muscle twitching
  • pounding, slow heartbeat
  • rapid weight gain
  • rapid, deep breathing
  • seizures
  • stomach cramps
  • stupor
  • swelling of the face, ankles, or hands

For Healthcare Professionals

Applies to epinephrine: compounding powder, inhalation aerosol, inhalation solution, injectable kit, injectable solution, intravenous solution, subcutaneous suspension

Nervous system

Nervous system side effects have included fear, agitation, anxiety, tenseness, restlessness, headache, tremor, dizziness, lightheadedness, nervousness, sleeplessness, excitability, weakness, and increased parkinsonian tremors. Complications associated with epidural anesthesia with epinephrine (the active ingredient contained in EpiPen) have included nerve root ischemia and clinical paralysis/plegia.[Ref]


Epinephrine can induce hypokalemia with resultant T wave changes on the electrocardiogram.

Rare cases of myocardial infarction have been associated with relatively small doses of epinephrine (the active ingredient contained in EpiPen) in patients at risk for coronary artery disease.

Rare cases of cardiomyopathy have been associated with brief and chronic exposure to epinephrine (including inhaled epinephrine). Animal studies have shown that catecholamines can cause an influx of calcium into myocardial cells, which may cause myocardial injury, particularly during periods of epinephrine-induced coronary vasoconstriction. Limited animal data suggest that calcium antagonists may protect against the cardiotoxic effects of catecholamines by preventing the generation of plasma borne cytotoxic compounds, which are probably free radicals.

Epinephrine may be more arrhythmogenic in some patients, such as patients with congenital long QT syndrome.[Ref]

Cardiovascular side effects have included elevations in heart rate or blood pressure in up to 55% and arrhythmias in 3% to 17% (including fatal ventricular arrhythmias) when used to treat cardiac arrest. In smaller doses, epinephrine has caused peripheral coronary arterial vasodilation, but in larger doses, epinephrine has caused diffuse vasoconstriction. This has caused increased peripheral vascular resistance, which was important in patients with coronary artery disease (worsened myocardial ischemia/angina) or hypertension (risk of emergent hypertension/stroke). Dilated cardiomyopathy and acute left ventricular dysfunction have been associated with the use of epinephrine.

Arrhythmias, including fatal ventricular fibrillation, have been reported in patients with underlying cardiac disease. Rapid rises in blood pressure have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease. Angina may occur in patients with coronary artery disease.[Ref]


Local side effects have included local tissue ischemia after repeated injections. Chronic IM epinephrine (the active ingredient contained in EpiPen) injections have induced local vasoconstriction, predisposing patients to Clostridial infections. Other local reactions have included injection site pallor, coldness and hypoesthesia or injury at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury.[Ref]


Psychiatric side effects have included agitation, disorientation, impaired memory, aggressive or assaultive behavior, hallucinations, and psychosis.[Ref]


Respiratory side effects have rarely included pulmonary edema. In some cases, acute left ventricular dysfunction has been documented in the presence of epinephrine-induced pulmonary edema. In some patients, epinephrine (the active ingredient contained in EpiPen) has precipitated severe, prolonged asthmatic attacks.[Ref]


Metabolic side effects have included severe metabolic acidosis because of elevated blood concentrations of lactic acid after prolonged use of intravenous epinephrine (the active ingredient contained in EpiPen) Catecholamines have induced glycogenolysis, elevated blood glucose and insulin concentrations, and hypokalemia. Rare cases of hyperglycemia and acidosis have been associated with high catecholamine states, such as anaphylaxis.[Ref]


Mattana and Singhal reviewed 420 consecutive cases of cardiac arrest and found a 28.6% incidence of acute renal failure (ARF) among patients who survived for at least 24 hours after cardiac arrest. Patients in whom ARF developed received markedly higher doses of epinephrine (the active ingredient contained in EpiPen) during resuscitative efforts than patients without ARF. High doses of epinephrine were associated with a longer duration of cardiopulmonary resuscitation. The patients with ARF had a significantly decreased survival rate. It is possible that patients with severe cardiac disease were less resuscitatable, required more epinephrine, and were prone to develop ARF anyway. Other data have failed to associated ARF with the use of high dose epinephrine.[Ref]

Renal side effects have included new or worsened renal insufficiency in adult survivors of cardiac arrest, adults who underwent epinephrine-assisted venography, and in rare pediatric cases.[Ref]


Hypersensitivity side effects have been extremely unusual. Contact dermatitis has been associated with ocularly applied epinephrine (the active ingredient contained in EpiPen) These reactions have typically presented with lid edema and a thick yellow discharge.[Ref]


Gastrointestinal side effects have included nausea and vomiting.[Ref]


1. Harrison PD "Paraplegia following epidural analgesia." Anaesthesia 30 (1975): 778-82

2. Kainuma M, Suzuki A "Convulsions after adrenaline administration during enflurane anaesthesia." Anaesthesia 41 (1986): 874-5

3. Dawkins CJ "An analysis of the complications of extradural and caudal block." Anaesthesia 24 (1969): 554-63

4. Mallampati SR, Liu PL, Knapp RM "Convulsions and ventricular tachycardia from bupivacaine with epinephrine: successful resuscitation." Anesth Analg 63 (1984): 856-9

5. Meyers EF, Ramirez RC, Boniuk I "Grand mal seizures after retrobulbar block." Arch Ophthalmol 96 (1978): 847

6. "Product Information. Epinephrine Hydrochloride Injection (epinephrine)." Abbott Pharmaceutical, Abbott Park, IL.

7. McManus BM, Fleury TA, Roberts WC "Fatal catecholamine crisis in pheochromocytoma: curable cause of cardiac arrest." Am Heart J 102 (1981): 930-2

8. Blue JA "Syncope in allergy." Ann Allergy 26 (1968): 561-8

9. Taub SJ "Reactions to aerosol therapy." Eye Ear Nose Throat Mon 48 (1969): 653-4

10. Ornato JP "High-dose epinephrine during resuscitation. A word of caution." JAMA 265 (1991): 1160-1

11. Kurachek SC, Rockoff MA "Inadvertent intravenous administration of racemic epinephrine." JAMA 253 (1985): 1441-2

12. Mor A, Eshel G, Aladjem M, Mundel G "Tachycardia and heart failure after ritual circumcision." Arch Dis Child 62 (1987): 80-1

13. Arditis J, Tsacona H, Giala M "Accidental administration of adrenaline during i.v. regional anaesthesia." Br J Anaesth 56 (1984): 923-4

14. Fletcher D, Mainardi JL, Brun-Buisson C, Lemaire F, Brochard L "Cardiac asthma presenting as status asthmaticus: deleterious effect of epinephrine therapy." Intensive Care Med 16 (1990): 466-8

15. Braren V "Circumcision complication." Clin Pediatr (Phila) 18 (1979): 639

16. Hirshom WI, Taylor RG, Sheehan JC "Arrhythmias produced by combinations of halothane and small amounts of vasopressor." Br J Oral Surg 2 (1964): 131-6

17. Ikezono E, Yasuda K, Hattori Y "Effects of propranolol on epinephrine-induced arrhythmias during halothane anesthesia in man and cats." Anesth Analg 48 (1969): 598-604

18. Clutter WE, Bier DM, Shah SD, Cryer PE "Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man." J Clin Invest 66 (1980): 94-101

19. Phillips S, Hutchinson SE, Bayly P, Hollway TE "Adrenaline-induced hypotension in neurosurgery." Br J Anaesth 70 (1993): 687-8

20. Speer F, Tapay NJ "Syncope in children following epinephrine." Ann Allergy 28 (1970): 50-4

21. Kalsner S "High-dose epinephrine in cardiopulmonary resuscitation." N Engl J Med 328 (1993): 735

22. Fyfe AI, Daly PA, Dorian P, Tough J "Reversible "cardiomyopathy" after accidental adrenaline overdose." Am J Cardiol 67 (1991): 318-9

23. Stewart MJ, Fraser DM, Boon N "Dilated cardiomyopathy associated with chronic overuse of an adrenaline inhaler." Br Heart J 68 (1992): 221-2

24. Haft JI "Cardiovascular injury induced by sympathetic catecholamines." Prog Cardiovasc Dis 17 (1974): 73-86

25. Forbes AM "Halothane, adrenaline and cardiac arrest." Anaesthesia 21 (1966): 22-7

26. Verrill PJ "Adverse reactions to local anaesthetics and vasoconstrictor drugs." Practitioner 214 (1975): 380-7

27. Kubota Y, Toyoda Y, Kubota H, Asada A "Epinephrine in local anesthetics does indeed produce hypokalemia and ECG changes." Anesth Analg 77 (1993): 867-8

28. Denton J, Schreiner RL, Pearson J "Circumcision complication. Reaction to treatment of local hemorrhage with topical epinephrine in high concentration." Clin Pediatr (Phila) 17 (1978): 285-6

29. Kochansky SW "Epinephrine. Use, adverse effects, and dosage calculation." AORN J 43 (1986): 852-5

30. Ersoz N, Finestone SC "Adrenaline-induced pulmonary oedema and its treatment. A report of two cases." Br J Anaesth 43 (1971): 709-12

31. Caldwell CC, Levkoff AH, Purohit DM "Paroxysmal supraventricular tachycardia in a neonate: a complication of racemic epinephrine inhalation for post-extubation stridor." Clin Pediatr (Phila) 16 (1977): 579-80

32. Lampe GH, Donegan JH, Rupp SM, Wauk LZ, Whitendale P, Fouts KE, Rose BM, Litt LL, Rampil IJ, Wilson CB, et al "Nitrous oxide and epinephrine-induced arrhythmias." Anesth Analg 71 (1990): 602-5

33. Tisdale JE, Patel RV, Webb Cr, Borzak S, Zarowitz BJ "Proarrhythmic effects of intravenous vasopressors." Ann Pharmacother 29 (1995): 269-81

34. Piscatelli RL, Fox LM "Myocardial injury from epinephrine overdosage." Am J Cardiol 21 (1968): 735-7

35. Ferry DR, Henry RL, Kern MJ "Epinephrine-induced myocardial infarction in a patient with angiographically normal coronary arteries." Am Heart J 111 (1986): 1193-5

36. Tang WC, Weil MH, Sun SJ, Noc M, Yang LY, Gazmuri RJ "Epinephrine increases the severity of postresuscitation myocardial dysfunction." Circulation 92 (1995): 3089-93

37. Brummett RE "Warning to otolaryngologists using local anesthetics containing epinephrine. Potential serious reaction occurring in patients treated with beta-adrenergic receptor blockers." Arch Otolaryngol 110 (1984): 561

38. Cabbabe EB, Behbahani PM "Cardiovascular reactions associated with the use of ketamine and epinephrine in plastic surgery." Ann Plast Surg 15 (1985): 50-6

39. Matsumiya N, Dohi S, Takahashi H, Kondo Y, Naito H "Cardiovascular collapse in an infant after caudal anesthesia with a lidocaine-epinephrine solution." Anesth Analg 65 (1986): 1074-6

40. Reisner LS, Lippmann M "Ventricular arrhythmias after epinephrine injection in enflurane and in halothane anesthesia." Anesth Analg 54 (1975): 468-70

41. Horrigan RW, Eger EI, Wilson C "Epinephrine-induced arrhythmias during enflurane anesthesia in man: a nonlinear dose-response relationship and dose-dependent protection from lidocaine." Anesth Analg 57 (1978): 547-50

42. Leon AS, Abrams WB "The role of catecholamines in producing arrhythmias." Am J Med Sci 262 (1971): 9-13

43. Whelan TV "Propranolol, epinephrine, and accelerated hypertension during hemodialysis." Ann Intern Med 106 (1987): 327

44. Sullivan TJ "Cardiac disorders in penicillin-induced anaphylaxis." JAMA 248 (1982): 2161-2

45. Karch SB "Coronary artery spasm induced by intravenous epinephrine overdose." Am J Emerg Med 7 (1989): 485-8

46. Saff R, Nahhas A, Fink JN "Myocardial infarction induced by coronary vasospasm after self- administration of epinephrine." Ann Allergy 70 (1993): 396-8

47. Cawson RA, Curson I, Whittington DR "The hazards of dental local anaesthetics." Br Dent J 154 (1983): 253-8

48. Richardson MG, Roark GL, Helfaer MA "Intraoperative epinephrine-induced torsades de pointes in a child with long QT syndrome." Anesthesiology 76 (1992): 647-9

49. Noronha-Dutra AA, Steen-Dutra EM, Woolf N "An antioxidant role for calcium antagonists in the prevention of adrenaline mediated myocardial and endothelial damage." Br Heart J 65 (1991): 322-5

50. Maguire WM, Reisdorff EJ, Smith D, Wiegenstein JG "Epinephrine-induced vasospasm reversed by phentolamine digital block." Am J Emerg Med 8 (1990): 46-7

51. Richards DA, Prichard BN, Hernandez R "Circulatory effects of noradrenaline and adrenaline before and after labetalol." Br J Clin Pharmacol 7 (1979): 371-8

52. Callaham M, Barton CW, Kayser S "Potential complications of high-dose epinephrine therapy in patients resuscitated from cardiac arrest." JAMA 265 (1991): 1117-22

53. Yagiela JA, Benoit PW, Buoncristiani RD, Peters MP, Fort NF "Comparison of myotoxic effects of lidocaine with epinephrine in rats and humans." Anesth Analg 60 (1981): 471-80

54. "Gas gangrene from adrenaline." Br Med J 1 (1968): 721

55. Teo WS, Balasubramaniam P "Gas gangrene after intramuscular injection of adrenaline." Clin Orthop 174 (1983): 206-7

56. Hartman MM "Capabilities and limitations of major drug groups in allergy: their role within current theories." Ann Allergy 27 (1969): 164-81

57. Woldorf NM, Pastore PN "Extreme epinephrine sensitivity with a general anesthesia." Arch Otolaryngol 96 (1972): 272-7

58. Rooke NT, Milne B "Acute pulmonary edema after regional anesthesia with lidocaine and epinephrine in a patient with chronic renal failure." Anesth Analg 63 (1984): 363-4

59. Thompson RG "Hypokalemia after resusitation." JAMA 250 (1983): 1026

60. Guerin JM, Meyer P, Habib Y "Is there a direct relationship between lactic acidosis and epinephrine administration?." Arch Intern Med 148 (1988): 980-1

61. Daniell HW "Hypokalemia after resusitation." JAMA 250 (1983): 1025

62. Feldschuh J, Gambino R "Extreme central acidosis from Abbott epinephrine." Am J Med 74 (1983): 30-2

63. Panacek EA, Sherman B "Lactic acidosis and insulin resistance associated with epinephrine in a patient with noninsulin-dependent diabetes mellitus." Arch Intern Med 148 (1988): 1879

64. Caruso M, Orszulak TA, Miles JM "Lactic acidosis and insulin resistance associated with epinephrine administration in a patient with non-insulin-dependent diabetes mellitus." Arch Intern Med 147 (1987): 1422-4

65. Maher TM "Hyperkalemia after resusitation." JAMA 250 (1983): 1025-6

66. Cardon PV, Weiss JL, Mueller PS "Effects of small intravenous doses of epinephrine on serum insulin, glucose tolerance and serum free fatty acids." Diabetes 23 (1974): 743-7

67. Mattana J, Singhal PC "High-dose epinephrine in cardiopulmonary resuscitation." N Engl J Med 328 (1993): discussion:735-6

68. Brown C, Martin D, Pepe P "High-dose epinephrine in cardiopulmonary resuscitation." N Engl J Med 328 (1993): 735-6

69. Levine DH, Levkoff AH, Pappu LD, Purohit DM "Renal failure and other serious sequelae of epinephrine toxicity in neonates." South Med J 78 (1985): 874-7

70. Cochran ST, Waisman J, Pagani JJ, Cahill P "Nephrotoxicity of epinephrine-assisted venography." Invest Radiol 17 (1982): 583-92

71. Alani SD, Alani MD "Allergic contact dermatits and conjunctivitis from epinephrine." Contact Dermatitis 2 (1976): 147-50

72. Gibbs RC "Allergic contact dermatitis to epinephrine." Arch Dermatol 101 (1970): 92-4

73. Romaguera C, Grimalt F "Contact dermatitis from epinephrine." Contact Dermatitis 6 (1980): 364

Not all side effects for EpiPen may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.