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Drug overview for EPIPEN 2-PAK (epinephrine):
Generic name: EPINEPHRINE (EP-i-NEF-rin)
Drug class: Beta-Adrenergic Agents
Therapeutic class: Cardiovascular Therapy Agents
Epinephrine is an endogenous catecholamine that is the active principle of the adrenal medulla; epinephrine acts directly on both alpha- and beta-adrenergic receptors.
No enhanced Uses information available for this drug.
Generic name: EPINEPHRINE (EP-i-NEF-rin)
Drug class: Beta-Adrenergic Agents
Therapeutic class: Cardiovascular Therapy Agents
Epinephrine is an endogenous catecholamine that is the active principle of the adrenal medulla; epinephrine acts directly on both alpha- and beta-adrenergic receptors.
No enhanced Uses information available for this drug.
DRUG IMAGES
EPIPEN 2-PAK 0.3 MG AUTO-INJCT
The following indications for EPIPEN 2-PAK (epinephrine) have been approved by the FDA:
Indications:
Anaphylaxis
Patient at risk of anaphylaxis
Professional Synonyms:
Anaphylactic reaction
Severe type I hypersensitivity reaction
Indications:
Anaphylaxis
Patient at risk of anaphylaxis
Professional Synonyms:
Anaphylactic reaction
Severe type I hypersensitivity reaction
The following dosing information is available for EPIPEN 2-PAK (epinephrine):
Dosage of epinephrine salts is expressed in terms of epinephrine. Dosage of racepinephrine hydrochloride is expressed in terms of racepinephrine; racepinephrine is about one-half as active as epinephrine.
For the emergency treatment of allergic reactions, including anaphylaxis, the usual adult dose of epinephrine is 0.2-0.5 mg (0.2-0.5 mL of a 1-mg/mL solution) administered IM or subcutaneously; the dose may be repeated every 5-15 minutes as necessary.
A maximum single dose of 0.5 mg in adults is recommended. IM administration is preferred since absorption and subsequent achievement of peak plasma concentrations may be slower and substantially delayed following subcutaneous administration of the drug if shock is present.
For self-administration of epinephrine using a prefilled auto-injector (e.g., EpiPen(R)), an IM or subcutaneous dose of 0.3 mg is recommended. For severe persistent anaphylaxis, repeated doses may be needed; if more than 2 sequential doses are needed, subsequent doses should be administered under direct medical supervision.
In extreme circumstances (e.g., anaphylactic shock, cardiac arrest, or no response to initial IM injections), IV administration may be necessary since absorption of epinephrine may be impaired with subcutaneous or IM administration. The usual adult IV dose of epinephrine for the treatment of anaphylaxis ranges from 0.1 to 0.25
mg (1-2.5 mL of a 0.1-mg/mL solution); the dose may be repeated every 5-15 minutes as needed. Although there is no established dosage for continuous IV infusions of epinephrine, some studies have demonstrated efficacy at IV infusion rates of 2-15 mcg/minute, titrated based on severity of the reaction and clinical response.
Patients with anaphylaxis who respond to therapy require observation for possible recurrence even if there is an intervening asymptomatic period; length of observation time has not been established. Symptoms may recur within 1-36 hours after the initial reaction. The duration of direct observation and monitoring after an episode of anaphylaxis should be individualized based on the severity and duration of the anaphylactic event as well as other factors (e.g., response to treatment, pattern of previous anaphylactic reactions, comorbidities, patient reliability, access to medical care).
Some experts suggest that patients with moderate to severe anaphylaxis should be observed for a minimum of 4-8 hours after treatment.
When used for cardiac resuscitation in adults, epinephrine doses ranging from 0.1-1 mg have been used. In ACLS guidelines, a standard dosage of epinephrine (defined as 1 mg every 3-5 minutes by IV/IO injection) is recommended during adult cardiac arrest.
Current evidence indicates that higher doses (e.g., 0.1-0.2 mg/kg) do not provide any benefits in terms of survival or neurologic outcomes compared with the standard dose and may be harmful.
The optimum dose of epinephrine during cardiac resuscitation has been a subject of controversy. Many clinicians had questioned the commonly used doses of 0.5-1 mg because of concern that these doses were not based on body weight, and thus may be lower than necessary for optimum cardiovascular effects.
Interest in high doses of epinephrine was stimulated by animal studies indicating that such doses (e.g., 0.045-0.2 mg/kg) provided optimal improvement in hemodynamics, including ROSC, and timely achievement of successful cardiopulmonary resuscitation (CPR). Results of several clinical studies, including randomized controlled studies, found no substantial improvement in survival rates to hospital discharge nor trend for improved neurologic outcomes in patients with cardiac arrest receiving higher than usual doses of epinephrine, despite evidence of increased rates of ROSC and higher initial resuscitation rates with high-dose therapy. A retrospective study of functional neurologic outcomes (assessed by measurement of cerebral performance category) of patients with ventricular fibrillation who received high IV dosages of epinephrine during cardiac resuscitation found that such dosages were independently associated with unfavorable neurologic outcomes.
Patients with unfavorable neurologic outcomes after resuscitation had received substantially higher median cumulative doses (i.e., 4 mg (range: 2-8 mg)) of epinephrine than those with favorable neurologic outcomes who received a median cumulative dose of 1 mg (range: less than 1-3 mg). These findings persisted after neurologic outcomes were stratified by duration of CPR and other potentially confounding conditions were considered. Based on the currently available evidence, the American Heart Association (AHA) states that it is reasonable to administer standard-dose epinephrine (1 mg every 3-5 minutes) during cardiac arrest in adults; high-dose epinephrine should not be used routinely, but may be considered in certain situations (e.g., overdosage of beta-adrenergic or calcium-channel blocking agents).
The optimal timing of epinephrine administration, particularly in relation to defibrillation, is not known and may vary based on patient-specific factors and resuscitation conditions. In adults with asystole or pulseless electrical activity (PEA), epinephrine may be given as soon as feasible after the onset of cardiac arrest based on studies demonstrating improved survival to hospital discharge and increased ROSC when the drug was administered early during the course of treatment for a nonshockable rhythm.
If IV or IO access cannot be established during cardiac arrest, epinephrine may be administered via the endotracheal route. Although the optimal dose of epinephrine administered via an endotracheal tube remains to be established, some experts state that typical doses should be 2-2.5 times those administered IV.
If epinephrine is used for hemodynamic support following cardiac resuscitation, the usual IV dosage in adults is 0.1-0.5 mcg/kg per minute; the infusion rate should be titrated to patient response.
If epinephrine is used for the treatment of symptomatic bradycardia in adults, an initial infusion rate of 2-10 mcg/minute has been recommended and should be titrated to patient response. Intravascular volume and support should be assessed as needed.
When used for pediatric advanced life support (PALS), the usual IV or IO dose of epinephrine is 0.01 mg/kg (0.1 mL/kg of a 0.1-mg/mL solution), up to a maximum single dose of 1 mg, and the usual dose of epinephrine administered via an endotracheal tube is 0.1 mg/kg (0.1 mL/kg of a 1-mg/mL solution), up to a maximum single dose of 2.5
mg. The same IV, IO, or endotracheal dose should be repeated every 3-5 minutes if needed. Higher doses are not recommended because of the potential for harm, particularly in cases of asphyxia, and lack of survival benefit.
AHA states, however, that high-dose epinephrine may be considered in exceptional circumstances (e.g., beta-adrenergic blocking agent overdose).
In a prospective, randomized, double-blind study of 68 children who received either 0.01 mg/kg (standard dose) or 0.1 mg/kg (high dose) of epinephrine as rescue therapy for in-hospital cardiac arrest after failure of CPR and an initial dose of 0.01
mg/kg (standard dose) of epinephrine, high-dose rescue therapy was not associated with any benefits. High-dose epinephrine rescue therapy did not improve the survival rate at 24 hours compared with standard-dose therapy, and appeared to be harmful in children with asphyxia-precipitated cardiac arrest. In addition, a trend toward reduced rate of survival at 24 hours was observed among children who received high-dose therapy as compared with standard-dose therapy.
Also, the rates of ROSC or survival to hospital discharge were not significantly different between the 2 groups.
For postresuscitation stabilization in pediatric patients, epinephrine may be administered by IV or IO infusion at a rate of 0.1-1 mcg/kg per minute; the rate of infusion should be adjusted based on patient response. Although low-dose IV infusions (less than 0.3 mcg/kg per minute) generally produce predominantly beta-adrenergic effects, while higher-dose IV infusions (exceeding 0.3 mcg/kg per minute) generally result in alpha-adrenergic vasoconstriction, there is substantial interindividual variation in response, and infusion dosage should be titrated to the desired effect.
The usual neonatal IV dose of epinephrine is 0.01-0.03 mg/kg (0.1-0.3 mL/kg of a 0.1-mg/mL solution).
AHA states that higher IV doses are not recommended; in pediatric and animal studies, administration of IV doses in the range of 0.1 mg/kg have been associated with exaggerated hypertension, decreased myocardial function, and worsening neurologic function. In addition, the sequence of hypotension followed by hypertension is likely to increase the risk of intracranial hemorrhage, especially in neonates.
IV administration of epinephrine (0.01-0.03 mg/kg per dose) is the preferred route in neonates, since there are limited data available on endotracheal administration of epinephrine. If the endotracheal route is used, doses of 0.01 or 0.03
mg/kg will likely be ineffective. Although safety and efficacy have not been established, endotracheal administration of a higher dose (0.05-0.1 mg/kg) while IV access is being obtained may be considered.
In one retrospective study in children and neonates who received either mean doses of 0.01 mg/kg (standard dose) or 0.12 mg/kg (high dose) of epinephrine administered IV, via an endotracheal tube, or by IO infusion during CPR after cardiac arrest occurring during a hospital stay, high doses of the drug were not associated with improvements in rates of ROSC, short- or long-term survival rates, or overall outcome scores.
In this study, the time to ROSC was substantially shorter in patients receiving standard doses of epinephrine than in those receiving higher doses. In addition, high-dose epinephrine may be associated with adverse effects such as increased myocardial oxygen consumption during cardiac resuscitation, a postarrest hyperadrenergic state with tachycardia, hypertension and ventricular ectopy, myocardial necrosis, and worse postarrest myocardial dysfunction. Additional clinical studies are needed to evaluate fully the optimum dosage regimen of epinephrine in pediatric patients.
For the emergency treatment of infants and children with bradycardia and cardiorespiratory compromise (with a palpable pulse), epinephrine may be given at a dose of 0.01 mg/kg (0.1 mL/kg of a 0.1-mg/mL solution) by IV/IO injection, and repeated every 3-5 minutes as needed; alternatively, an endotracheal dose of 0.1 mg/kg (0.1 mL/kg of a 1-mg/mL solution) may be given if IV/IO access is not available.
For the treatment of severe asthma exacerbations when orally inhaled, selective short-acting beta2-adrenergic agonists are not available, an expert panel of the National Asthma Education and Prevention Program (NAEPP) states that epinephrine 0.3-0.5 mg may be given subcutaneously every 20 minutes for 3 doses in adults and adolescents older than 12 years of age.
Alternatively, some clinicians recommend a subcutaneous epinephrine dose of 0.01 mg/kg (using a 1-mg/mL solution), divided into 3 doses of approximately 0.3 mg each, administered at 20-minute intervals.
For the treatment of severe asthma exacerbations in children 12 years of age or younger, 0.01 mg/kg of epinephrine (0.01 mL/kg using a 1-mg/mL solution), but no more than 0.3-0.5
mg per dose, may be administered by subcutaneous injection at 20-minute intervals for 3 doses.
For the treatment of bronchospasm in adults, some manufacturers recommend an epinephrine dose of 0.1-0.25 mg (1-2.5 mL of a 0.1-mg/mL solution) by slow IV injection.
If IV administration of epinephrine is required for the management of asthma attacks in pediatric patients, some clinicians recommend a slow IV injection of 0.01 mg/kg in neonates and an initial IV dose of 0.05 mg (which may be repeated at 20- to 30-minute intervals) in infants.
For the temporary relief of mild symptoms of intermittent asthma, the usual dose of 2.25% racepinephrine inhalation solution (equivalent to 1% epinephrine) in adults and children 4 years of age or older is 1-3 inhalations; doses should not be repeated more often than every 3 hours. Patients should be advised to seek medical assistance immediately if symptoms are not relieved within 20 minutes or become worse.
For the emergency treatment of allergic reactions, including anaphylaxis, the usual adult dose of epinephrine is 0.2-0.5 mg (0.2-0.5 mL of a 1-mg/mL solution) administered IM or subcutaneously; the dose may be repeated every 5-15 minutes as necessary.
A maximum single dose of 0.5 mg in adults is recommended. IM administration is preferred since absorption and subsequent achievement of peak plasma concentrations may be slower and substantially delayed following subcutaneous administration of the drug if shock is present.
For self-administration of epinephrine using a prefilled auto-injector (e.g., EpiPen(R)), an IM or subcutaneous dose of 0.3 mg is recommended. For severe persistent anaphylaxis, repeated doses may be needed; if more than 2 sequential doses are needed, subsequent doses should be administered under direct medical supervision.
In extreme circumstances (e.g., anaphylactic shock, cardiac arrest, or no response to initial IM injections), IV administration may be necessary since absorption of epinephrine may be impaired with subcutaneous or IM administration. The usual adult IV dose of epinephrine for the treatment of anaphylaxis ranges from 0.1 to 0.25
mg (1-2.5 mL of a 0.1-mg/mL solution); the dose may be repeated every 5-15 minutes as needed. Although there is no established dosage for continuous IV infusions of epinephrine, some studies have demonstrated efficacy at IV infusion rates of 2-15 mcg/minute, titrated based on severity of the reaction and clinical response.
Patients with anaphylaxis who respond to therapy require observation for possible recurrence even if there is an intervening asymptomatic period; length of observation time has not been established. Symptoms may recur within 1-36 hours after the initial reaction. The duration of direct observation and monitoring after an episode of anaphylaxis should be individualized based on the severity and duration of the anaphylactic event as well as other factors (e.g., response to treatment, pattern of previous anaphylactic reactions, comorbidities, patient reliability, access to medical care).
Some experts suggest that patients with moderate to severe anaphylaxis should be observed for a minimum of 4-8 hours after treatment.
When used for cardiac resuscitation in adults, epinephrine doses ranging from 0.1-1 mg have been used. In ACLS guidelines, a standard dosage of epinephrine (defined as 1 mg every 3-5 minutes by IV/IO injection) is recommended during adult cardiac arrest.
Current evidence indicates that higher doses (e.g., 0.1-0.2 mg/kg) do not provide any benefits in terms of survival or neurologic outcomes compared with the standard dose and may be harmful.
The optimum dose of epinephrine during cardiac resuscitation has been a subject of controversy. Many clinicians had questioned the commonly used doses of 0.5-1 mg because of concern that these doses were not based on body weight, and thus may be lower than necessary for optimum cardiovascular effects.
Interest in high doses of epinephrine was stimulated by animal studies indicating that such doses (e.g., 0.045-0.2 mg/kg) provided optimal improvement in hemodynamics, including ROSC, and timely achievement of successful cardiopulmonary resuscitation (CPR). Results of several clinical studies, including randomized controlled studies, found no substantial improvement in survival rates to hospital discharge nor trend for improved neurologic outcomes in patients with cardiac arrest receiving higher than usual doses of epinephrine, despite evidence of increased rates of ROSC and higher initial resuscitation rates with high-dose therapy. A retrospective study of functional neurologic outcomes (assessed by measurement of cerebral performance category) of patients with ventricular fibrillation who received high IV dosages of epinephrine during cardiac resuscitation found that such dosages were independently associated with unfavorable neurologic outcomes.
Patients with unfavorable neurologic outcomes after resuscitation had received substantially higher median cumulative doses (i.e., 4 mg (range: 2-8 mg)) of epinephrine than those with favorable neurologic outcomes who received a median cumulative dose of 1 mg (range: less than 1-3 mg). These findings persisted after neurologic outcomes were stratified by duration of CPR and other potentially confounding conditions were considered. Based on the currently available evidence, the American Heart Association (AHA) states that it is reasonable to administer standard-dose epinephrine (1 mg every 3-5 minutes) during cardiac arrest in adults; high-dose epinephrine should not be used routinely, but may be considered in certain situations (e.g., overdosage of beta-adrenergic or calcium-channel blocking agents).
The optimal timing of epinephrine administration, particularly in relation to defibrillation, is not known and may vary based on patient-specific factors and resuscitation conditions. In adults with asystole or pulseless electrical activity (PEA), epinephrine may be given as soon as feasible after the onset of cardiac arrest based on studies demonstrating improved survival to hospital discharge and increased ROSC when the drug was administered early during the course of treatment for a nonshockable rhythm.
If IV or IO access cannot be established during cardiac arrest, epinephrine may be administered via the endotracheal route. Although the optimal dose of epinephrine administered via an endotracheal tube remains to be established, some experts state that typical doses should be 2-2.5 times those administered IV.
If epinephrine is used for hemodynamic support following cardiac resuscitation, the usual IV dosage in adults is 0.1-0.5 mcg/kg per minute; the infusion rate should be titrated to patient response.
If epinephrine is used for the treatment of symptomatic bradycardia in adults, an initial infusion rate of 2-10 mcg/minute has been recommended and should be titrated to patient response. Intravascular volume and support should be assessed as needed.
When used for pediatric advanced life support (PALS), the usual IV or IO dose of epinephrine is 0.01 mg/kg (0.1 mL/kg of a 0.1-mg/mL solution), up to a maximum single dose of 1 mg, and the usual dose of epinephrine administered via an endotracheal tube is 0.1 mg/kg (0.1 mL/kg of a 1-mg/mL solution), up to a maximum single dose of 2.5
mg. The same IV, IO, or endotracheal dose should be repeated every 3-5 minutes if needed. Higher doses are not recommended because of the potential for harm, particularly in cases of asphyxia, and lack of survival benefit.
AHA states, however, that high-dose epinephrine may be considered in exceptional circumstances (e.g., beta-adrenergic blocking agent overdose).
In a prospective, randomized, double-blind study of 68 children who received either 0.01 mg/kg (standard dose) or 0.1 mg/kg (high dose) of epinephrine as rescue therapy for in-hospital cardiac arrest after failure of CPR and an initial dose of 0.01
mg/kg (standard dose) of epinephrine, high-dose rescue therapy was not associated with any benefits. High-dose epinephrine rescue therapy did not improve the survival rate at 24 hours compared with standard-dose therapy, and appeared to be harmful in children with asphyxia-precipitated cardiac arrest. In addition, a trend toward reduced rate of survival at 24 hours was observed among children who received high-dose therapy as compared with standard-dose therapy.
Also, the rates of ROSC or survival to hospital discharge were not significantly different between the 2 groups.
For postresuscitation stabilization in pediatric patients, epinephrine may be administered by IV or IO infusion at a rate of 0.1-1 mcg/kg per minute; the rate of infusion should be adjusted based on patient response. Although low-dose IV infusions (less than 0.3 mcg/kg per minute) generally produce predominantly beta-adrenergic effects, while higher-dose IV infusions (exceeding 0.3 mcg/kg per minute) generally result in alpha-adrenergic vasoconstriction, there is substantial interindividual variation in response, and infusion dosage should be titrated to the desired effect.
The usual neonatal IV dose of epinephrine is 0.01-0.03 mg/kg (0.1-0.3 mL/kg of a 0.1-mg/mL solution).
AHA states that higher IV doses are not recommended; in pediatric and animal studies, administration of IV doses in the range of 0.1 mg/kg have been associated with exaggerated hypertension, decreased myocardial function, and worsening neurologic function. In addition, the sequence of hypotension followed by hypertension is likely to increase the risk of intracranial hemorrhage, especially in neonates.
IV administration of epinephrine (0.01-0.03 mg/kg per dose) is the preferred route in neonates, since there are limited data available on endotracheal administration of epinephrine. If the endotracheal route is used, doses of 0.01 or 0.03
mg/kg will likely be ineffective. Although safety and efficacy have not been established, endotracheal administration of a higher dose (0.05-0.1 mg/kg) while IV access is being obtained may be considered.
In one retrospective study in children and neonates who received either mean doses of 0.01 mg/kg (standard dose) or 0.12 mg/kg (high dose) of epinephrine administered IV, via an endotracheal tube, or by IO infusion during CPR after cardiac arrest occurring during a hospital stay, high doses of the drug were not associated with improvements in rates of ROSC, short- or long-term survival rates, or overall outcome scores.
In this study, the time to ROSC was substantially shorter in patients receiving standard doses of epinephrine than in those receiving higher doses. In addition, high-dose epinephrine may be associated with adverse effects such as increased myocardial oxygen consumption during cardiac resuscitation, a postarrest hyperadrenergic state with tachycardia, hypertension and ventricular ectopy, myocardial necrosis, and worse postarrest myocardial dysfunction. Additional clinical studies are needed to evaluate fully the optimum dosage regimen of epinephrine in pediatric patients.
For the emergency treatment of infants and children with bradycardia and cardiorespiratory compromise (with a palpable pulse), epinephrine may be given at a dose of 0.01 mg/kg (0.1 mL/kg of a 0.1-mg/mL solution) by IV/IO injection, and repeated every 3-5 minutes as needed; alternatively, an endotracheal dose of 0.1 mg/kg (0.1 mL/kg of a 1-mg/mL solution) may be given if IV/IO access is not available.
For the treatment of severe asthma exacerbations when orally inhaled, selective short-acting beta2-adrenergic agonists are not available, an expert panel of the National Asthma Education and Prevention Program (NAEPP) states that epinephrine 0.3-0.5 mg may be given subcutaneously every 20 minutes for 3 doses in adults and adolescents older than 12 years of age.
Alternatively, some clinicians recommend a subcutaneous epinephrine dose of 0.01 mg/kg (using a 1-mg/mL solution), divided into 3 doses of approximately 0.3 mg each, administered at 20-minute intervals.
For the treatment of severe asthma exacerbations in children 12 years of age or younger, 0.01 mg/kg of epinephrine (0.01 mL/kg using a 1-mg/mL solution), but no more than 0.3-0.5
mg per dose, may be administered by subcutaneous injection at 20-minute intervals for 3 doses.
For the treatment of bronchospasm in adults, some manufacturers recommend an epinephrine dose of 0.1-0.25 mg (1-2.5 mL of a 0.1-mg/mL solution) by slow IV injection.
If IV administration of epinephrine is required for the management of asthma attacks in pediatric patients, some clinicians recommend a slow IV injection of 0.01 mg/kg in neonates and an initial IV dose of 0.05 mg (which may be repeated at 20- to 30-minute intervals) in infants.
For the temporary relief of mild symptoms of intermittent asthma, the usual dose of 2.25% racepinephrine inhalation solution (equivalent to 1% epinephrine) in adults and children 4 years of age or older is 1-3 inhalations; doses should not be repeated more often than every 3 hours. Patients should be advised to seek medical assistance immediately if symptoms are not relieved within 20 minutes or become worse.
USP has changed its labeling standard for single-entity drug products to no longer allow the use of ratios to express drug concentrations. This labeling change was prompted by numerous reports of serious medication errors caused by confusion with different ratio expressions. Effective May 1, 2016, all single-entity preparations of epinephrine injection, USP should be labeled only in terms of strength per mL (i.e., mg/mL).
While concentrations of some epinephrine preparations were historically expressed in ratios (e.g., 1:1000 or 1:10,000), such designation is no longer acceptable because of the risk of dosing errors. Epinephrine usually is administered by IM, subcutaneous, or IV injection, or by continuous IV infusion. Epinephrine also has been administered by intraosseous (IO) injection+ in the setting of advanced cardiovascular life support (ACLS), generally when IV access is not readily available; onset of action and systemic concentrations are comparable to those achieved with venous administration.
If vascular access (IV or IO) cannot be established during cardiac arrest, epinephrine may be administered endotracheally; however, this method of administration results in lower plasma concentrations compared with the same dose given intravascularly. Epinephrine also has been administered by intracardiac injection (into the left ventricular chamber) during cardiac arrest; however, this route of administration is not recommended in current ACLS guidelines. The appropriate concentration and route of administration of epinephrine should be selected carefully; serious adverse effects (e.g., cerebral hemorrhage) have occurred after concentrated solutions of epinephrine intended for IM administration were administered IV.
Because of the risks associated with IV use, epinephrine generally should be administered by the IV route only in extreme situations (such as in the treatment of septic or anaphylactic shock, cardiac arrest, or when the patient is unresponsive to multiple IM injections). Dilute solutions of epinephrine (e.g., 0.1 mg/mL) should always be used when administering the drug IV. Commercially available epinephrine solutions for IM or subcutaneous injection are tenfold more concentrated (1 mg/mL) and should not be administered IV without dilution.
Solutions of epinephrine should be inspected visually for particulate matter and discoloration prior to administration. Epinephrine injection must not be used if it is discolored or cloudy or contains any particulate matter.
While concentrations of some epinephrine preparations were historically expressed in ratios (e.g., 1:1000 or 1:10,000), such designation is no longer acceptable because of the risk of dosing errors. Epinephrine usually is administered by IM, subcutaneous, or IV injection, or by continuous IV infusion. Epinephrine also has been administered by intraosseous (IO) injection+ in the setting of advanced cardiovascular life support (ACLS), generally when IV access is not readily available; onset of action and systemic concentrations are comparable to those achieved with venous administration.
If vascular access (IV or IO) cannot be established during cardiac arrest, epinephrine may be administered endotracheally; however, this method of administration results in lower plasma concentrations compared with the same dose given intravascularly. Epinephrine also has been administered by intracardiac injection (into the left ventricular chamber) during cardiac arrest; however, this route of administration is not recommended in current ACLS guidelines. The appropriate concentration and route of administration of epinephrine should be selected carefully; serious adverse effects (e.g., cerebral hemorrhage) have occurred after concentrated solutions of epinephrine intended for IM administration were administered IV.
Because of the risks associated with IV use, epinephrine generally should be administered by the IV route only in extreme situations (such as in the treatment of septic or anaphylactic shock, cardiac arrest, or when the patient is unresponsive to multiple IM injections). Dilute solutions of epinephrine (e.g., 0.1 mg/mL) should always be used when administering the drug IV. Commercially available epinephrine solutions for IM or subcutaneous injection are tenfold more concentrated (1 mg/mL) and should not be administered IV without dilution.
Solutions of epinephrine should be inspected visually for particulate matter and discoloration prior to administration. Epinephrine injection must not be used if it is discolored or cloudy or contains any particulate matter.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| EPIPEN 2-PAK 0.3 MG AUTO-INJCT | Maintenance | Adults inject 0.3 milliliter (0.3 mg) by intramuscular route once as needed for anaphylaxis |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| EPINEPHRINE 0.3 MG AUTO-INJECT | Maintenance | Adults inject 0.3 milliliter (0.3 mg) by intramuscular route once as needed for anaphylaxis |
The following drug interaction information is available for EPIPEN 2-PAK (epinephrine):
There are 0 contraindications.
There are 0 severe interactions.
There are 1 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Sympathomimetics/Rauwolfia Alkaloids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Reserpine depletes catecholamine stores within the peripheral vascular adrenergic nerve endings, thus indirect acting sympathomimetics are unable to trigger the release of catecholamines. The reserpine-induced catecholamine release increases sensitivity to the effects of direct acting sympathomimetics. CLINICAL EFFECTS: Increased effects of direct acting sympathomimetics. Decreased effects of indirect acting sympathomimetics. Mixed acting sympathomimetics will show effects based on the predominance of either direct or indirect activity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If these agents are administered concurrently, monitor blood pressure. The dose of the sympathomimetic may need to be adjusted. DISCUSSION: This interaction has been well documented in animal studies and human case reports have confirmed the interaction. Reserpine has been shown to decrease the response to epinephrine administered for hypotension. Reserpine has also been shown to decrease the effectiveness of ophthalmic epinephrine, a direct acting sympathomimetic. Ophthalmic phenylephrine has been shown to decrease the hypotensive effects of reserpine. |
RESERPINE |
The following contraindication information is available for EPIPEN 2-PAK (epinephrine):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 0 contraindications.
There are 12 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Angina |
| Angle-closure glaucoma |
| Cardiac arrhythmia |
| Cardiogenic shock |
| Cerebral arteriosclerosis |
| Congenital long QT syndrome |
| Coronary artery disease |
| Dilated cardiomyopathy |
| Hemorrhagic shock |
| Hypertension |
| Hyperthyroidism |
| Sinus tachycardia |
There are 1 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Diabetes mellitus |
The following adverse reaction information is available for EPIPEN 2-PAK (epinephrine):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 22 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Hypertension |
| Rare/Very Rare |
|---|
|
Acute myocardial infarction Angina Cardiac arrhythmia Cardiomyopathy Cerebrovascular accident Chest pain Extravasation injury Gangrene Hyperglycemia Hypokalemia Intracranial bleeding Kidney disease with reduction in glomerular filtration rate (GFr) Lactic acidosis Myocardial ischemia Necrotizing fasciitis Paradoxical bronchospasm Pulmonary edema Supraventricular tachycardia Ventricular arrhythmias Ventricular fibrillation Ventricular premature beats |
There are 25 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Dizziness General weakness Headache disorder Nausea Nervousness Pallor Palpitations Symptoms of anxiety Tachycardia Tremor Vomiting |
None. |
| Rare/Very Rare |
|---|
|
Acute cognitive impairment Agitation Apprehension Blanching of skin Drowsy Hyperhidrosis Hypoesthesia Injection site infection Injection site sequelae Memory impairment Oliguria Panic disorder Paresthesia Xerostomia |
The following precautions are available for EPIPEN 2-PAK (epinephrine):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Epinephrine usually inhibits spontaneous or oxytocin-induced contractions of the pregnant human uterus and may delay the second stage of labor. In dosages sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with hemorrhage. If used during pregnancy, epinephrine may cause anoxia to the fetus and/or spontaneous abortion.
When administered in advanced cardiovascular life support (ACLS) during cardiac resuscitation, epinephrine may decrease blood flow to the uterus; however, the woman must be resuscitated for survival of the fetus. Some manufacturers state that epinephrine should be avoided during the second stage of labor; parenteral administration of the drug to maintain blood pressure during spinal anesthesia for delivery can cause acceleration of fetal heart rate and should not be used in obstetric patients when maternal systolic/diastolic blood pressure exceeds 130/80 mm Hg. Epinephrine should be administered cautiously by oral inhalation to pregnant patients.
Epinephrine should be used during pregnancy only if the potential benefits justify the possible risks to the fetus. There is some evidence to support that epidural administration of some local anesthetics (e.g., lidocaine) with epinephrine during labor is safe.
When administered in advanced cardiovascular life support (ACLS) during cardiac resuscitation, epinephrine may decrease blood flow to the uterus; however, the woman must be resuscitated for survival of the fetus. Some manufacturers state that epinephrine should be avoided during the second stage of labor; parenteral administration of the drug to maintain blood pressure during spinal anesthesia for delivery can cause acceleration of fetal heart rate and should not be used in obstetric patients when maternal systolic/diastolic blood pressure exceeds 130/80 mm Hg. Epinephrine should be administered cautiously by oral inhalation to pregnant patients.
Epinephrine should be used during pregnancy only if the potential benefits justify the possible risks to the fetus. There is some evidence to support that epidural administration of some local anesthetics (e.g., lidocaine) with epinephrine during labor is safe.
No enhanced Lactation information available for this drug.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for EPIPEN 2-PAK (epinephrine):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for EPIPEN 2-PAK (epinephrine)'s list of indications:
| Anaphylaxis | |
| T78.0 | Anaphylactic reaction due to food |
| T78.00 | Anaphylactic reaction due to unspecified food |
| T78.00xA | Anaphylactic reaction due to unspecified food, initial encounter |
| T78.01 | Anaphylactic reaction due to peanuts |
| T78.01xA | Anaphylactic reaction due to peanuts, initial encounter |
| T78.02 | Anaphylactic reaction due to shellfish (crustaceans) |
| T78.02xA | Anaphylactic reaction due to shellfish (crustaceans), initial encounter |
| T78.03 | Anaphylactic reaction due to other fish |
| T78.03xA | Anaphylactic reaction due to other fish, initial encounter |
| T78.04 | Anaphylactic reaction due to fruits and vegetables |
| T78.04xA | Anaphylactic reaction due to fruits and vegetables, initial encounter |
| T78.05 | Anaphylactic reaction due to tree nuts and seeds |
| T78.05xA | Anaphylactic reaction due to tree nuts and seeds, initial encounter |
| T78.06 | Anaphylactic reaction due to food additives |
| T78.06xA | Anaphylactic reaction due to food additives, initial encounter |
| T78.07 | Anaphylactic reaction due to milk and dairy products |
| T78.07xA | Anaphylactic reaction due to milk and dairy products, initial encounter |
| T78.08 | Anaphylactic reaction due to eggs |
| T78.08xA | Anaphylactic reaction due to eggs, initial encounter |
| T78.09 | Anaphylactic reaction due to other food products |
| T78.09xA | Anaphylactic reaction due to other food products, initial encounter |
| T78.2 | Anaphylactic shock, unspecified |
| T78.2xxA | Anaphylactic shock, unspecified, initial encounter |
| T80.5 | Anaphylactic reaction due to serum |
| T80.51 | Anaphylactic reaction due to administration of blood and blood products |
| T80.51xA | Anaphylactic reaction due to administration of blood and blood products, initial encounter |
| T80.52 | Anaphylactic reaction due to vaccination |
| T80.52xA | Anaphylactic reaction due to vaccination, initial encounter |
| T80.59 | Anaphylactic reaction due to other serum |
| T80.59xA | Anaphylactic reaction due to other serum, initial encounter |
| T88.6 | Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered |
| T88.6xxA | Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, initial encounter |
| Patient at risk of anaphylaxis | |
| T78.0 | Anaphylactic reaction due to food |
| T78.00 | Anaphylactic reaction due to unspecified food |
| T78.00xA | Anaphylactic reaction due to unspecified food, initial encounter |
| T78.00xD | Anaphylactic reaction due to unspecified food, subsequent encounter |
| T78.00xS | Anaphylactic reaction due to unspecified food, sequela |
| T78.01 | Anaphylactic reaction due to peanuts |
| T78.01xA | Anaphylactic reaction due to peanuts, initial encounter |
| T78.01xD | Anaphylactic reaction due to peanuts, subsequent encounter |
| T78.01xS | Anaphylactic reaction due to peanuts, sequela |
| T78.02 | Anaphylactic reaction due to shellfish (crustaceans) |
| T78.02xA | Anaphylactic reaction due to shellfish (crustaceans), initial encounter |
| T78.02xD | Anaphylactic reaction due to shellfish (crustaceans), subsequent encounter |
| T78.02xS | Anaphylactic reaction due to shellfish (crustaceans), sequela |
| T78.03 | Anaphylactic reaction due to other fish |
| T78.03xA | Anaphylactic reaction due to other fish, initial encounter |
| T78.03xD | Anaphylactic reaction due to other fish, subsequent encounter |
| T78.03xS | Anaphylactic reaction due to other fish, sequela |
| T78.04 | Anaphylactic reaction due to fruits and vegetables |
| T78.04xA | Anaphylactic reaction due to fruits and vegetables, initial encounter |
| T78.04xD | Anaphylactic reaction due to fruits and vegetables, subsequent encounter |
| T78.04xS | Anaphylactic reaction due to fruits and vegetables, sequela |
| T78.05 | Anaphylactic reaction due to tree nuts and seeds |
| T78.05xA | Anaphylactic reaction due to tree nuts and seeds, initial encounter |
| T78.05xD | Anaphylactic reaction due to tree nuts and seeds, subsequent encounter |
| T78.05xS | Anaphylactic reaction due to tree nuts and seeds, sequela |
| T78.06 | Anaphylactic reaction due to food additives |
| T78.06xA | Anaphylactic reaction due to food additives, initial encounter |
| T78.06xD | Anaphylactic reaction due to food additives, subsequent encounter |
| T78.06xS | Anaphylactic reaction due to food additives, sequela |
| T78.07 | Anaphylactic reaction due to milk and dairy products |
| T78.07xA | Anaphylactic reaction due to milk and dairy products, initial encounter |
| T78.07xD | Anaphylactic reaction due to milk and dairy products, subsequent encounter |
| T78.07xS | Anaphylactic reaction due to milk and dairy products, sequela |
| T78.08 | Anaphylactic reaction due to eggs |
| T78.08xA | Anaphylactic reaction due to eggs, initial encounter |
| T78.08xD | Anaphylactic reaction due to eggs, subsequent encounter |
| T78.08xS | Anaphylactic reaction due to eggs, sequela |
| T78.09 | Anaphylactic reaction due to other food products |
| T78.09xA | Anaphylactic reaction due to other food products, initial encounter |
| T78.09xD | Anaphylactic reaction due to other food products, subsequent encounter |
| T78.09xS | Anaphylactic reaction due to other food products, sequela |
| T78.2 | Anaphylactic shock, unspecified |
| T78.2xxA | Anaphylactic shock, unspecified, initial encounter |
| T78.2xxD | Anaphylactic shock, unspecified, subsequent encounter |
| T78.2xxS | Anaphylactic shock, unspecified, sequela |
| T80.5 | Anaphylactic reaction due to serum |
| T80.51 | Anaphylactic reaction due to administration of blood and blood products |
| T80.51xA | Anaphylactic reaction due to administration of blood and blood products, initial encounter |
| T80.51xD | Anaphylactic reaction due to administration of blood and blood products, subsequent encounter |
| T80.51xS | Anaphylactic reaction due to administration of blood and blood products, sequela |
| T80.52 | Anaphylactic reaction due to vaccination |
| T80.52xA | Anaphylactic reaction due to vaccination, initial encounter |
| T80.52xD | Anaphylactic reaction due to vaccination, subsequent encounter |
| T80.52xS | Anaphylactic reaction due to vaccination, sequela |
| T80.59 | Anaphylactic reaction due to other serum |
| T80.59xA | Anaphylactic reaction due to other serum, initial encounter |
| T80.59xD | Anaphylactic reaction due to other serum, subsequent encounter |
| T80.59xS | Anaphylactic reaction due to other serum, sequela |
| T88.6 | Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered |
| T88.6xxA | Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, initial encounter |
| T88.6xxD | Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, subsequent encounter |
| T88.6xxS | Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, sequela |
| Z87.892 | Personal history of anaphylaxis |
| Z91.010 | Allergy to peanuts |
| Z91.011 | Allergy to milk products |
| Z91.012 | Allergy to eggs |
| Z91.013 | Allergy to seafood |
| Z91.018 | Allergy to other foods |
| Z91.02 | Food additives allergy status |
| Z91.03 | Insect allergy status |
| Z91.030 | Bee allergy status |
Formulary Reference Tool