alpha-Adrenergic Agonist

Epinephrine

Approved 29 Jul 2014IntravenousSolution

The FDA lists this product in 24 strengths and forms.

Indications

Epinephrine is a non-selective alpha and beta adrenergic agonist indicated: To increase mean arterial blood pressure in adult patients with hypotension associated with septic shock. ( 1.1 ) For emergency treatment of allergic reactions (Type 1), including anaphylaxis. ( 1.2 ) For induction and maintenance of mydriasis during intraocular surgery. ( 1.3 )

1.1 Hypotension associated with Septic Shock Epinephrine Injection USP, 1 mg/mL is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock.

1.2Anaphylaxis

Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. The signs and symptoms associated with anaphylaxis include flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with hypotension, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, airway swelling, laryngospasm, bronchospasm, pruritus, urticaria or angioedema, swelling of the eyelids, lips, and tongue.

1.3Induction and Maintenance of Mydriasis during Intraocular Surgery Induction

and maintenance of mydriasis during intraocular surgery.

Contraindications

None. None. ( 4 )

Warnings and precautions

Monitor patient for acute severe hypertension. ( 5.1 ) Avoid extravasation into tissues, which can cause local necrosis. ( 5.2 ) Do not inject into buttocks, digits, hands, or feet. ( 5.3 ) Potential for pulmonary edema, which may be fatal. ( 5.4 ) May constrict renal blood vessels and decrease urine formation. ( 5.5 ) May induce potentially serious cardiac arrhythmias or aggravate angina pectoris, particularly in patients with underlying heart disease.

( 5.6 ) Rare cases of serious skin and soft tissue infections have been reported following epinephrine injection. Advise patients to seek medical care if they develop signs or symptoms of infection. ( 5.8 ) Patients with hyperthyroidism, Parkinson's disease, diabetes, and pheochromocytoma are at greater risk of having adverse reactions when used intravenously, intramuscularly, or subcutaneously. ( 5.9 )

At a glance

Brand name: Epinephrine
Pharmacologic class: alpha-Adrenergic Agonist, beta-Adrenergic Agonist, Catecholamine
Route: Intravenous
Dosage form: Solution
Applicant: Bpi Labs
Status: Discontinued
FDA approval: 29 Jul 2014
Application: NDA205029-003

Indications

1.1 Hypotension associated with Septic Shock Epinephrine Injection USP, 1 mg/mL is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock.

1.2Anaphylaxis

1.3Induction and Maintenance of Mydriasis during Intraocular Surgery Induction

and maintenance of mydriasis during intraocular surgery.

Warnings and precautions

Interactions

Drugs antagonizing pressor effects of epinephrine α-blockers, such as phentolamine Vasodilators, such as nitrates Diuretics Antihypertensives Ergot alkaloids Drugs potentiating pressor effects of epinephrine Sympathomimetics β-blockers, such as propranolol Tricyclic anti-depressants Monoamine oxidase (MAO) inhibitors Catechol-O-methyl transferase (COMT) inhibitors, such as entacapone Clonidine Doxapram Oxytocin Drugs potentiating arrhythmogenic effects of epinephrine.

Patients who are concomitantly receiving any of the following drugs should be observed carefully for the development of cardiac arrhythmias [see Warnings and Precautions (5.6) and Adverse Reactions (6) ]. β-blockers, such as propranolol Cyclopropane or halogenated hydrocarbon anesthetics, such as halothane Antihistamines Thyroid hormones Diuretics Cardiac glycosides, such as digitalis glycosides Quinidine Drugs potentiating hypokalemic effects of epinephrine Potassium depleting diuretics Corticosteroids Theophylline Epinephrine should not be used to counteract circulatory collapse or hypotension caused by phenothiazines, as a reversal of the pressor effects of epinephrine may result in further lowering of blood pressure.

Epinephrine may antagonize the neuronal blockade produced by guanethidine resulting in decreased antihypertensive effect and requiring increased dosage of the latter. Drugs that counter the pressor effects of epinephrine include alpha blockers, vasodilators such as nitrates, diuretics, antihypertensives and ergot alkaloids. ( 7 ) Drugs that potentiate the effects of epinephrine include sympathomimetics, beta blockers, tricyclic antidepressants, MAO inhibitors, COMT inhibitors, clonidine, doxapram, oxytocin, levothyroxine sodium, and certain antihistamines.

( 7 ) Drugs that increase the arrhythmogenic potential of epinephrine include beta blockers, cyclopropane and halogenated hydrocarbon anesthetics, quinidine, antihistamines, exogenous thyroid hormones, diuretics, and cardiac glycosides. Observe for development of cardiac arrhythmias. ( 7 ) Potassium-depleting drugs, including corticosteroids, diuretics, and theophylline, potentiate the hypokalemic effects of epinephrine.

( 7 )

Adverse reactions

Most common adverse reactions to systemically administered epinephrine are headache; anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; peripheral coldness; nausea/vomiting; and/or respiratory difficulties. Arrhythmias, including fatal ventricular fibrillation, rapid rises in blood pressure producing cerebral hemorrhage, and angina have occurred. ( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact BPI Labs, LLC at (727) 471-0850 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Adverse

Reactions associated with Epinephrine Infusion (for Hypotension associated with Septic Shock) The following adverse reactions associated with the infusion of epinephrine were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Cardiovascular disorders: tachycardia, supraventricular tachycardia, ventricular arrhythmias, myocardial ischemia, myocardial infarction, limb ischemia, pulmonary edema Gastrointestinal disorders: Nausea, vomiting General disorders and administrative site conditions: Chest pain, extravasation, Metabolic: hypoglycemia, hyperglycemia, insulin resistance, hypokalemia, lactic acidosis Nervous system disorders: Headache, nervousness, paresthesia, tremor, stroke, central nervous system bleeding Psychiatric disorders: Excitability Renal disorders: Renal insufficiency Respiratory: Pulmonary edema, rales Skin and subcutaneous tissue disorders: Diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation

6.2Adverse

Reactions associated with Intramuscular or Subcutaneous Use (for Anaphylaxis) Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism [see Warnings and Precautions (5.9) ].

Due to the lack of randomized, controlled clinical trials of epinephrine for the treatment of anaphylaxis, the true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine. Adverse reactions reported in observational trials, case reports, and studies are listed below by body system: Cardiovascular: angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, and ventricular ectopy.

Angina may occur in patients with coronary artery disease [see Warnings and Precautions (5.6) ]. Arrhythmias, including fatal ventricular fibrillation, have occurred, particularly in patients with underlying organic heart disease or patients receiving drugs that sensitize the heart to arrhythmias [see Warnings and Precautions (5.6) ]. Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see Warnings and Precautions (5.6) ].

Respiratory: respiratory difficulties. Neurological: dizziness, disorientation, excitability, headache, impaired memory, lightheadedness, nervousness, panic, psychomotor agitation, sleepiness, tingling, tremor, and weakness. Psychiatric: anxiety, apprehensiveness, restlessness. Gastrointestinal: nausea, vomiting. Skin: sweating. Other: Patients with Parkinson’s disease may experience psychomotor agitation or a temporary worsening of symptoms [see Warnings and Precautions (5.9) ].

Diabetic patients may experience transient increases in blood sugar [see Warnings and Precautions (5.9) ]. Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see Warnings and Precautions (5.3) ]. Adverse events experienced as a result of an injection into these areas include increased heart rate, local reactions including injection site pallor, coldness, hypoesthesia, and tissue loss, or injury at the injection site resulting in bruising, bleeding, discoloration, erythema, and skeletal injury.

Injection into the buttock has resulted in cases of gas gangrene [see Warnings and Precautions (5.3) ]. Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection in the thigh [see Warnings and Precautions (5.8) ].

6.3Adverse Reactions Associated with Intraocular Use (for Mydriasis)

Epinephrine products containing sodium bisulfite have been associated with corneal endothelial damage when used in the eye at undiluted concentrations (1 mg/mL). Although this Epinephrine product contains no sulfites or preservatives, warning is still advised [see Warnings and Precautions (5.7) ]. To report SUSPECTED ADVERSE REACTIONS, contact BPI Labs LLC at (727) 471-0850 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Epinephrine

Indications

1.2Anaphylaxis

1.3Induction and Maintenance of Mydriasis during Intraocular Surgery Induction

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Epinephrine

Indications

1.2Anaphylaxis

1.3Induction and Maintenance of Mydriasis during Intraocular Surgery Induction

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Hypertension When Epinephrine

5.2Extravasation and Tissue Necrosis with Intravenous Infusion When Epinephrine

5.3Incorrect Locations of Injection for Anaphylaxis When Epinephrine

5.4Pulmonary Edema When Epinephrine

5.5Renal Impairment

5.6Cardiac Arrhythmias and Ischemia

5.7Injury with Undiluted Intraocular Solution

5.8Serious Infections at the Injection Site

5.9Other Disease Interactions

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Teratogenic Effects: Pregnancy Category C:

Adverse reactions

6.1Adverse

6.2Adverse

6.3Adverse Reactions Associated with Intraocular Use (for Mydriasis)

Composition

Strengths and forms

Official product information