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Epinephrine (adrenaline) (oral inhalation): Pediatric drug information

Epinephrine (adrenaline) (oral inhalation): Pediatric drug information
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Brand Names: US
  • Asthmanefrin Refill [OTC];
  • S2 (Racepinephrine) [OTC]
Brand Names: Canada
  • S2 (Racepinephrine) [DSC]
Therapeutic Category
  • Adrenergic Agonist Agent;
  • Antiasthmatic;
  • Bronchodilator;
  • Sympathomimetic
Dosing: Pediatric
Bronchospasm, relief of mild asthma symptoms

Bronchospasm, relief of mild asthma symptoms: Note: Not recommended for routine management and treatment of asthma (Ref).

Nebulization solution: Children ≥4 years and Adolescents: Handheld bulb nebulizer: Add 0.5 mL (1 vial) of 2.25% solution to nebulizer; 1 to 3 inhalations; may repeat dose after at least 3 hours if needed. Maximum daily dose: 12 inhalations/24 hours.

Metered-dose inhaler: Children ≥12 years and Adolescents: Oral inhalation: 1 inhalation once; if symptoms not relieved after 1 minute, may repeat 1 inhalation; wait ≥4 hours between additional doses; maximum daily dose: 8 inhalations/24 hours

Croup, airway edema; moderate to severe

Croup (laryngotracheobronchitis), airway edema; moderate to severe: Limited data available: Infants, Children, and Adolescents: Note: Typically relief of symptoms occurs within 10 to 30 minutes and lasts 2 to 3 hours; patients should be observed for rapid symptom recurrence and possible repeat treatment.

Racemic epinephrine (2.25% solution): Nebulization: 0.05 to 0.1 mL/kg (maximum dose: 0.5 mL) diluted in 2 to 3 mL NS, may repeat dose every 20 minutes; others have reported use of 0.5 mL as a fixed dose for all patients; use lower end of dosing range for younger infants (Ref).

L-epinephrine (using parenteral 1 mg/mL solution): Nebulization: 0.5 mL/kg of 1:1,000 solution (maximum dose: 5 mL) diluted in NS, may repeat dose every 20 minutes; Note: Racemic epinephrine 10 mg = 5 mg L-epinephrine (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adult

(For additional information see "Epinephrine (adrenaline) (oral inhalation): Drug information")

Asthma, mild intermittent symptoms

Asthma, mild intermittent symptoms: Note: Primary utility is in acute anaphylaxis with edema; nonselective beta agonists (eg, epinephrine) are not recommended for the routine management and treatment of asthma due to their potential for excessive cardiac stimulation, especially in high doses (Ref).

Metered-dose inhaler: Oral inhalation: 1 inhalation (0.125 mg) once; if symptoms not relieved after 1 minute, may repeat; wait ≥4 hours between additional doses (maximum dose: 8 inhalations per 24 hours).

Nebulization solution: Hand-bulb nebulizer: 1 to 3 inhalations of 2.25% (1 vial); may repeat dose after ≥3 hours as needed (maximum dose: 12 inhalations per 24 hours).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

There are no adverse reactions listed in the manufacturer's labeling.

Contraindications

OTC labeling: When used for self-medication, do not use with or within 2 weeks of discontinuing an MAOI or in patients without a diagnosis of asthma.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart disease and/or hypertension.

• Diabetes: Use with caution in patients with diabetes mellitus.

• Increased intraocular pressure/glaucoma: Use with caution in patients with increased intraocular pressure or glaucoma.

• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

• Psychiatric conditions: Use with caution in patients with psychiatric or emotional conditions.

• Seizures: Use with caution in patients with a history seizure disorder

• Thyroid disease: Use with caution in patients with thyroid disease.

Dosage form specific issues:

• Nebulization solution: Do not use if product is brown in color or cloudy.

Other warnings/precautions:

• Self-medication (OTC use): When used for self-medication (OTC), notify health care provider if symptoms are not relieved in 20 minutes or become worse; if >8 inhalations of Primatene Mist, >12 inhalations of Asthmanefrin, S2 are needed in 24 hours; if >9 inhalations in 24 hours for ≥3 days a week of Asthmanefrin, S2 are needed, or if >2 asthma attacks have occurred within a week. Discontinue use and notify health care provider if your asthma is getting worse, or if difficulty sleeping, rapid heartbeat, tremors, nervousness, or seizure occur. The product should not be used more frequently or at higher doses than recommended.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Nebulization Solution, Inhalation:

Asthmanefrin Refill: 2.25% (1 ea) [contains edetate disodium]

Nebulization Solution, Inhalation [preservative free]:

S2 (Racepinephrine): 2.25% (1 ea) [sulfite free; contains edetate disodium]

Generic Equivalent Available: US

No

Pricing: US

Nebulization (Asthmanefrin Refill Inhalation)

2.25% (per each): $1.00

Nebulization (S2 (Racepinephrine) Inhalation)

2.25% (per each): $1.80

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Nebulization Solution, Inhalation:

S2 (Racepinephrine): 2.25% ([DSC])

Administration: Pediatric

Nebulization solution:

Asthma symptoms: Hand-held rubber bulb nebulizer. Add contents of 1 vial (0.5 mL) of solution to nebulizer; dilution not required.

Croup: Dilute prior to nebulization (Ref).

Metered-dose inhaler: Shake canister prior to each use. Prime inhaler prior to first use with 4 test sprays into the air (away from face). Before each use, shake inhaler and then spray into the air 1 time. Wash inhaler after each day of use by running water through the mouthpiece for 30 seconds.

Administration: Adult

For oral inhalation only.

Metered-dose inhaler: Before first use, shake inhaler then spray into the air 4 separate times. Before each inhalation, shake then spray into the air 1 time. Wash inhaler after each day of use by running water through the mouthpiece for 30 seconds; shake off excess water and air-dry overnight.

Nebulization solution: For use in a hand-held rubber bulb nebulizer. Add contents of one vial (0.5 mL) of solution to nebulizer.

Storage/Stability

Nebulization solution: Store between 2°C to 25°C (36°F to 77°F). Protect from light and freezing; avoid excessive heat.

Metered-dose inhaler: Store between 15°C and 25°C (59°F to 77°F). Do not store near open flame or heat >49°C (120°F). Do not puncture or incinerate.

Use

Temporary relief of mild symptoms of intermittent asthma (ie, shortness of breath, tightness of chest, wheezing) (OTC products: Bulb nebulization solution: FDA approved in ages ≥4 years and adults; Metered-dose inhaler: FDA approved in ages ≥12 years and adults); has also been used to treat upper airway obstruction and croup. Note: Not recommended for routine management and treatment of asthma (GINA 2018; NAEPP 2007).

Medication Safety Issues
Sound-alike/look-alike issues:

EPINEPHrine may be confused with ePHEDrine

Metabolism/Transport Effects

Substrate of COMT

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

Alpha1-Blockers: May diminish the therapeutic effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Beta-Blockers (Beta1 Selective): May diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Beta-Blockers (Nonselective): May enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Beta-Blockers (with Alpha-Blocking Properties): May diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Bromocriptine: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider therapy modification

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Chloroprocaine (Systemic): May enhance the hypertensive effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification

COMT Inhibitors: May increase the serum concentration of COMT Substrates. Risk C: Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Inhalational Anesthetics: May enhance the arrhythmogenic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination

Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy

Lisuride: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Risk X: Avoid combination

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk X: Avoid combination

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Pergolide: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Management: If possible, avoid coadministration of direct-acting alpha-/beta-agonists and serotonin/norepinephrine reuptake inhibitors. If coadministered, monitor for increased sympathomimetic effects (eg, increased blood pressure, chest pain, headache). Risk D: Consider therapy modification

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy

Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Risk D: Consider therapy modification

Food Interactions

Avoid food or beverages that contain caffeine.

Dietary Considerations

Avoid food or beverages that contain caffeine.

Pregnancy Considerations

Epinephrine crosses the placenta following injection (Sandler 1964).

Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes). Maternal asthma symptoms should be monitored monthly during pregnancy. However, epinephrine inhalation is not recommended for routine management and treatment of asthma (ERS/TSANZ [Middleton 2020]; GINA 2023).

Monitoring Parameters

Monitor asthma symptoms, FEV1, peak flow and/or other pulmonary function tests, blood pressure, heart rate, CNS stimulation

Mechanism of Action

Stimulates alpha-, beta1-, and beta2-adrenergic receptors resulting in relaxation of smooth muscle of the bronchial tree, cardiac stimulation (increasing myocardial oxygen consumption), and dilation of skeletal muscle vasculature; small doses can cause vasodilation via beta2-vascular receptors; large doses may produce constriction of skeletal and vascular smooth muscle

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Bronchodilation: Inhalation: ~1 minute

Distribution: Does not cross blood-brain barrier

Metabolism: Taken up into the adrenergic neuron and metabolized by monoamine oxidase and catechol-o-methyltransferase; circulating drug hepatically metabolized

Excretion: Urine (as inactive metabolites, metanephrine, and sulfate and hydroxy derivatives of mandelic acid, small amounts as unchanged drug)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Medihaler;
  • (AU) Australia: Adrenalin chloride | Adrenaline;
  • (BR) Brazil: Dyspne inhalante;
  • (DE) Germany: Adrenalin;
  • (FI) Finland: Adrenalin medihal;
  • (GB) United Kingdom: Medihaler-epi;
  • (JP) Japan: Asthsedan | Vaponefrin hisamitsu | Vaponefrin tokyo mi shokai;
  • (KR) Korea, Republic of: Epinephrine | Racepinephrine;
  • (NO) Norway: Micronefrin | Primatene;
  • (PR) Puerto Rico: Adrenalin chloride | Epinephrine | S-2;
  • (SE) Sweden: Adrenalin
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  4. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. https://ginasthma.org/2023-gina-main-report/. Updated 2023. Accessed August 23, 2023.
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