EPIPEN E Z PEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPIPEN E Z PEN (EPIPEN E Z PEN).
Epinephrine is a direct-acting sympathomimetic amine that acts on alpha- and beta-adrenergic receptors. Alpha-adrenergic stimulation increases peripheral vascular resistance, reversing hypotension and improving coronary perfusion. Beta-adrenergic stimulation causes bronchodilation, positive inotropy, and chronotropy.
| Metabolism | Epinephrine is rapidly metabolized in the liver and other tissues by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) to inactive metabolites. Up to 40% of a dose is excreted as metanephrine in urine. |
| Excretion | Epinephrine is rapidly metabolized in the liver and other tissues by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Approximately 80-90% of an intravenous dose is excreted in the urine as inactive metabolites (metanephrine, vanillylmandelic acid, 3,4-dihydroxymandelic acid) with less than 5% excreted unchanged. |
| Half-life | The terminal elimination half-life of epinephrine is approximately 2-3 minutes when administered intravenously. The short half-life necessitates repeated doses or continuous infusion for sustained effect. |
| Protein binding | Epinephrine is weakly bound to plasma proteins; binding is approximately 15-20% mainly to albumin. |
| Volume of Distribution | The volume of distribution (Vd) is approximately 0.3-0.7 L/kg, indicating distribution primarily into extracellular fluid and highly perfused tissues. |
| Bioavailability | Bioavailability after intramuscular injection is approximately 50-70% due to local vasoconstriction limiting absorption. Subcutaneous bioavailability is similarly lower due to vasoconstriction. Intravenous administration yields 100% bioavailability. |
| Onset of Action | Intramuscular (auto-injector): Rapid onset within 5-10 minutes. Subcutaneous: Onset within 5-15 minutes. Intravenous: Immediate onset within seconds. |
| Duration of Action | Intramuscular: Duration of action is approximately 20-30 minutes, which is short due to rapid metabolism. Clinical note: Duration may be extended with higher doses or in shock states; may require repeat doses for persistent anaphylaxis. |
0.3 mg intramuscularly every 5-15 minutes as needed for anaphylaxis. Administer into anterolateral thigh.
| Dosage form | INJECTABLE |
| Renal impairment | No adjustment required for renal impairment. Epinephrine undergoes rapid metabolism and renal elimination is not significant. |
| Liver impairment | No adjustment required for hepatic impairment. Epinephrine metabolism may be affected in severe hepatic disease but dosing adjustment based on Child-Pugh is not established. |
| Pediatric use | For body weight <30 kg (approximately <12 years): 0.15 mg intramuscularly. For body weight ≥30 kg: 0.3 mg intramuscularly. Administer into anterolateral thigh. May repeat every 5-15 minutes as needed. |
| Geriatric use | Use standard adult dose (0.3 mg intramuscularly) with caution due to increased risk of adverse cardiovascular effects; consider dose reduction if clinically appropriate. Monitor blood pressure and heart rate closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EPIPEN E Z PEN (EPIPEN E Z PEN).
| Breastfeeding | Epinephrine is excreted into human breast milk. M/P ratio: estimated 0.5-1.0 (limited data). Oral bioavailability to infant is low due to first-pass metabolism. Use with caution; monitor infant for irritability, tachycardia. Compatible with breastfeeding during maternal anaphylaxis treatment. |
| Teratogenic Risk | Epinephrine (EPIPEN E Z PEN) is a sympathomimetic amine. Animal studies are inadequate. In humans, epinephrine crosses the placenta. First trimester: potential for reduced uterine blood flow, fetal hypoxia; avoid unless life-threatening. Second/third trimester: may cause uterine vasoconstriction, fetal tachycardia; use only for anaphylaxis. High doses may increase risk of congenital anomalies (case reports). Overall, benefit of treating maternal anaphylaxis outweighs risks. |
■ FDA Black Box Warning
None. However, epinephrine is a high-alert medication due to risk of dosing errors.
| Serious Effects |
["Hypersensitivity to epinephrine or any component of the product (e.g., sulfites)","In patients with narrow-angle glaucoma (unless benefit outweighs risk)","During labor (may delay second stage; use in pregnancy only if clearly needed)","Concurrent use with nonselective beta-blockers (may cause severe hypertension)"]
| Precautions | ["Do not inject into buttocks, digits, or veins; avoid intra-arterial administration","Use with caution in patients with cardiovascular disease, hypertension, diabetes, hyperthyroidism, or in elderly patients","May cause pulmonary edema, stroke, or arrhythmias due to vasoconstriction and increased cardiac workload","Epinephrine is heat-sensitive and should not be refrigerated or exposed to extreme temperatures"] |
| Food/Dietary | No specific food interactions. However, avoid foods that may trigger anaphylaxis (e.g., peanuts, tree nuts, shellfish, eggs, milk, soy, wheat). Identify and avoid known allergens. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, ECG, and signs of uterine hypertonicity. Fetal: monitor fetal heart rate (tachycardia, decelerations). Assess for fetal distress in pregnant women with anaphylaxis. |
| Fertility Effects | No evidence of impaired fertility in animal studies. Reproductive toxicity: high doses may cause uterine contractions; no human data on fertility effects. |
| Clinical Pearls | Administer intramuscularly into mid-outer thigh. Can be given through clothing. Do not inject into gluteal muscle or vein. After use, place back in tube and seek emergency medical attention. Monitor for biphasic anaphylaxis. Contraindicated in patients with hypersensitivity to epinephrine or sulfites (though benefit outweighs risk in anaphylaxis). |
| Patient Advice | Carry EpiPen at all times and check expiration date regularly. · Know the signs of anaphylaxis: difficulty breathing, swelling, hives, low blood pressure. · Use only in mid-outer thigh; do not inject into buttocks or hand. · After injection, hold in place for 3 seconds, then massage injection site. · Seek emergency medical care immediately after use. · Inform all healthcare providers and family about your epinephrine auto-injector. · Store at room temperature, protect from light and freezing. |