epinephrine (EpiPen, EpiPen Jr, Adrenaclick, Auvi-Q, Adrenalin)

Dosing and uses of EpiPen, EpiPen Jr (epinephrine)

• Adult
• Pediatric

 

Adult dosage forms and strengths

autoinjector (EpiPen, Twinject, Adrenaclick, Auvi-Q)

• 0.15mg/0.15mL
• 0.3mg/0.3mg

injectable solution

• 0.1mg/mL (1:10,000)
• 1mg/mL (1:1000)

 

Cardiac Arrest

1 mg IV/IO q3-5min PRN; may administer up to 0.2 mg/kg if no response

Dose >1 mg not shown to improve survival or neurological oucomes as compared to standard dosing; not recommended

ET: 2-2.5 mg q3-5min until IV/IO access established or spontaneous circulation restored

 

Asthma, Severe/Anaphylaxis

0.2-0.5 mg IM/SC q5-15min (1:1,000 solution; 1 mg/mL), clinician may shorten 5-min interval between injections for more frequent administration if deemed appropriate

0.1 mg (1:10,000 solution; 0.1mg/mL) IV at rate of 1-4 mcg/min over 5 min to prevent the need to repeat injections frequently OR may initiate with infusion at 5-15 mcg/min (with crystalloid administration); IV administration should only be done in patients who are profoundly hypotensive or are in cardiopulmonary arrest refractory to volume resuscitation and several epinephrine injections

Autoinjector: 0.3 mg (contents of 1 autoinjector) SC/IM once in anterolateral aspect of the thigh; may repeat dose after 5-15 minutes if symptoms persist

 

Symptomatic Bradycardia (Off-label)

Unresponsive to atropine or pacing: 2-10 mcg//min by IV infusion or 0.1-0.5 mcg/kg/min (7-35 mcg/min in 70 kg patient); titrate to patient response

 

Administration

Do not administer autoinjector IV; give only in outer thigh to ensure SC or IM administration

Discard remaining volume after dose has been administered

 

Pediatric dosage forms and strengths

autoinjector (EpiPen, Twinject, Adrenaclick, Auvi-Q)

• 0.15mg
• 0.3mg

injectable solution

• 0.1mg/mL (1:10,000)
• 1mg/mL (1:1000)

 

Asystole/Pulseless Arrest (Off-label)

1:10,000 solution: 0.01 mg/kg (0.1 mg/mL) IO/IV; not to exceed 1 mg; repeat q3-5min until return of spontaneous circulation

0.1 mg/kg (0.1 mL/kg of 1:1000 solution; 1 mg/mL) endotracheal; not to exceed 2.5 mg q3-5min until IO/IVP access established or spontaneous circulation achieved; flush with 5 mL of normal saline immediately after administration

 

Symptomatic Bradycardia (Off-label)

1:10,000 solution: 0.01 mg/kg IO/IV q3-5min; not to exceed 1 mg

1:1,000 solution: 0.1 mg/kg (0.1mL/kg) of endotracheal q3-5min if necessary; flush each dose with at least 5 mL isotonic sodium chloride injection

Neonates (<28 days old): 0.01-0.03 mg/kg IVP (1:10,000 solution) q3-5min; higher doses not recommended

Neonate IV access not available: 0.05-0.1 mg/kg endotracheal tube (1:10,000 soluiton); lower doses not effective; follow each dose with at least 5 mL isotonic sodium chloride injection

 

Asthma/Anaphylaxis

0.01 mg/kg (0.01 mL/kg of 1:1,000 solution; 1 mg/mL) IM/SC q5-15min , clinician may shorten 5-min interval between injections for more frequent administration if deemed appropriate

Autoinjector

• Weight <30 kg: 0.15 mg (contents of 1 autoinjector) SC/IM once; may repeat dose q5-15min
• Weight ≥30 kg: 0.3 mg (contents of 1 autoinjector) SC/IM once; may repeat dose q5-15min

 

Administration

When administering to a child, to minimize risk of injection related injury, hold leg firmly in place and limit movement prior to and during an injection; injection may be repeated every 5-10 min as necessary; for IM administration, use a needle long enough (at least 1/2 inch to 5/8 inch) to ensure injection is administered into muscle; monitor patient clinically for severity of allergic reaction and potential cardiac effects of drug, with repeat doses titrated to effect; do not administer repeated injections at same site, as resulting vasoconstriction may cause tissue necrosis

Do not administer autoinjector IV; give only in outer thigh to ensure SC or IM administration

Discard remaining volume after dose has been administered

 

EpiPen, EpiPen Jr (epinephrine) adverse (side) effects

Frequency not defined

Angina

Anxiety

Apprehensiveness

Cardiac arrhythmias

Dizziness

Dyspnea

Flushing

Headache

Hypertension

Nausea

Nervousness

Pallor

Palpitations

Respiratory difficulties

Restlessness

Sweating

Tachycardia

Tremor

Vasoconstriction

Vomiting

Weakness

 

Postmarketing Reports

Necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene)

 

Warnings

Contraindications

There are no contraindications for life-threatening situations

Nonanaphylactic shock

Narrow-angle glaucoma

Coadministration during genral anesthesia with halogenated hydrocarbons or cyclopropane

Labor

Situations where vasopressors may be contraindicated, including thyrotoxicosis, diabetes

Maternal blood pressure in excess of 130/80 mm Hg in hypertension and other cardiovascular disorders

 

Cautions

Use caution in patients with cardiac disease, angina (especially with history of CAD) or that are receiving drugs that sensitize the myocardium; treatment may induce cardiac arrhythmias

Pulmonary edema may occur as the result of cardiac stimulation and peripheral constriction

Decreased urine output may occur as the result of renal blood vessel constriction

Use caution in cerebrovascular insufficiency

Use with caution in patients with hypertension, diabetes mellitus, thyroid disease, prostatic hypertrophy, geriatric patients, pregnancy, and previous hospitalization for asthma

Use caution when administering in conjunction with anesthesia in fingers, toes, ears, nose, or genitalia, due to potential for ischemia due to vasoconstriction

Use caution in concomitant use of digitalis, mercurial diuretics, quinidine, or drugs that may sensitize the heart to arrhythmias

Accidental injection into hands, digits, or feet may result in local reactions including injection site coldness, pallor, and hypoesthesia or injury resulting in bruising, discoloration, erythema, bleeding, or skeletal injury

Rapid IV administration, although necessary in pulesless arrest, may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Patients that are sulfite-sensitive, should still be treated during a serious allergic reaction or other emergency even if products available contain sulfites

May cause worsening of symptoms in patients with Parkinson disease

Avoid extravasation; ensure proper needle or catheter placement prior to and during infusion

Correct blood volume depletion before administering any vasopressor

Injection into buttock may not provide effective treatment of anaphylaxis

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), reported at injection site following injection for anaphylaxis; to decrease risk, do not inject into buttock; advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at epinephrine injection site; cleansing with alcohol does not kill bacterial spores, and therefore, does not lower risk of infection

Multiple-dose vial not for ophthalmic use; contains chlorobutanol which may be harmful to corneal endothelium

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Unknown if excreted into breast milk; use caution

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of EpiPen, EpiPen Jr (epinephrine)

Mechanism of action

Strong alpha-adrenergic effects, which cause an increase in cardio output and HR, a decrease in renal perfusion and PVR, and a variable effect on BP, resulting in systemic vasoconstriction and increased vascular permeability

Strong beta1- and moderate beta2-adrenergic effects, resulting in bronchial smooth muscle relaxation

Secondary relaxation effect on smooth muscle of stomach, intestine, uterus, and urinary bladder

 

Absorption

Onset: 5-10 min (SC); 1 min (inhalation)

Duration: 4 hr

 

Metabolism

Metabolized by MAO and COMT in adrenergic neuron

Metabolites: Metadrenaline, sulfate conjugates, and hydroxy derivatives of mandelic acid (inactive)

 

Elimination

Excretion: Urine

 

Administration

IV Incompatibilities

Solution: Na-bicarbonate 5%, Ionosol PSL, Ionosol T/D5

Additive: Aminophylline, hyaluronidase, mephentermine, Na-bicarbonate

Syringe: Na-bicarbonate(?)

Y-site: Ampicillin, thiopentaL

Not specified: Atropine, carbenicillin, diazepam, erythromycin, lidocaine

 

IV Compatibilities

Solution: D5W, D10W, dextrose-Ringer's, dextrose-saline, NS, LR, Ringer's

Additive: Amikacin, cimetidine, dobutamine, floxacillin, furosemide, metaraminol, ranitidine, verapamiL

Syringe: Caffeine, doxapram, heparin, milrinone

Y-site: Amiodarone, atracurium, bivalirudin, CaCl2, Ca gluconate, cefpirome, cisatracurium, dexmedetomidine, diltiazem, dobutamine, dopamine, famotidine, fenoldopam, fentanyl, furosemide, heparin, Hextend, hydrocortisone Na succinate, hydromorphone, inamrinone, labetalol, levofloxacin, lorazepam, midazolam, milrinone, morphine SO4, nicardipine, nitroglycerin, norepinephrine, pancuronium, phytonadione, KCl, propofol, ranitidine, remifentanil, nitroprusside, tirofiban, vasopressin, vecuronium, vitamin B/C, warfarin

Not specified: Meperidine

 

IV Preparation

Solution: 1 mg in 250 mL D5W or NS (4 mcg/mL) to make up concentration of 15-60 mL/hr (1-4 mcg/min)

 

IV Administration

Central line; infusion pump required

Do not mix with alkaline solutions

Discard after 24 hours or if solution is discolored or contains precipitate

Store in light-resistant container