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EPINEPHrine (Oral Inhalation)


General


Pronunciation

(ep i NEF rin)


Brand Names: U.S.

  • Asthmanefrin Refill [OTC]
  • Asthmanefrin Starter Kit [OTC]
  • Micronefrin [OTC] [DSC]
  • S2 [OTC]

Indications


Use: Labeled Indications

OTC labeling: Treatment of bronchospasm associated with bronchial asthma


Contraindications


Oral inhalation (OTC labeling): Concurrent use or within 2 weeks of MAO inhibitors


Dosing and Administration


Dosing: Adult

Bronchospasm, relief of mild asthma symptoms: Nebulization: Racemic epinephrine (2.25% solution): OTC labeling: Hand-bulb nebulizer: Add 0.5 mL to nebulizer; 1 to 3 inhalations, may repeat dose after at least 3 hours if needed. Do not exceed 12 inhalations in 24 hours.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Bronchospasm, relief of mild asthma symptoms: Children ≥4 years and Adolescents: Nebulization: Racemic epinephrine (2.25% solution): OTC labeling: Hand-bulb nebulizer: Add 0.5 mL to nebulizer; 1 to 3 inhalations; may repeat dose after at least 3 hours if needed. Do not exceed 12 inhalations in 24 hours. Note: Not recommended for routine management and treatment of asthma (GINA 2015; NAEPP 2007)

Croup (laryngotracheobronchitis), airway edema (off-label use): Infants, Children, and Adolescents: Nebulization: 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): 0.05 to 0.1 mL/kg (maximum dose: 0.5 mL) diluted in 2 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 (Hegenbarth 2008; Rosekrans 1998; Rotta 2003; Wright 2002)

L-epinephrine (using parenteral 1 mg/mL solution): 0.5 mL/kg of 1 mg/mL solution (maximum dose: 5 mL) diluted in NS, may repeat dose every 20 minutes; Note: Racemic epinephrine 10 mg = 5 mg L-epinephrine (Hegenbarth 2008)


Dosing: Renal Impairment

There are no dosage adjustment provided in manufacturers labeling.


Dosing: Hepatic Impairment

There are no dosage adjustment provided in manufacturers labeling.


Reconstitution

Oral inhalation: S2, Asthmanefrin: If using jet nebulizer, must be diluted with 3 to 5 mL NS. If using handheld rubber bulb nebulizer, dilution is not required.


Administration

Oral inhalation: If using jet nebulizer: Administer diluted over ~15 minutes. If using handheld rubber bulb nebulizer, dilution is not required.


Storage

S2, Asthmanefrin: Store between 2 ‚ °C to 20 ‚ °C (36 ‚ °F to 68 ‚ °F). Protect from light.


Dosage Forms/Strengths


Dosage Forms

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

Nebulization Solution, Inhalation:

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

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

Micronefrin: 2.25% (15 mL [DSC], 30 mL [DSC])

Nebulization Solution, Inhalation [preservative free]:

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


Drug Interactions

Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Beta-Blockers: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Consider therapy modification

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

COMT Inhibitors: May decrease the metabolism of COMT Substrates. Monitor therapy

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

Ergot Derivatives: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination

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

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

MAO Inhibitors: May enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Avoid combination

Promethazine: May diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). 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. Consider therapy modification

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

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

Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Management: Avoid, if possible, the use of direct-acting 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. Consider therapy modification


Monitoring Parameters

FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium; asthma symptoms


Adverse Reactions


There are no adverse reactions listed in the manufacturers labeling.


Warnings/Precautions


Disease-related concerns:

- Cardiovascular disease: Use with caution in patients with cardiovascular diseases (eg, arrhythmias, coronary artery disease, hypertension).

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

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

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

- Self medication (OTC use): Prior to self-medication, patients should contact healthcare provider. The product should only be used in persons with a diagnosis of asthma. If symptoms are not relieved in 20 minutes or become worse do not continue to use the product - seek immediate medical assistance. The product should not be used more frequently or at higher doses than recommended unless directed by a health care provider. This product should not be used in patients who have required hospitalization for asthma or if a patient is taking prescription medication for asthma. Use with caution in patients with prostate enlargement or urinary retention. Do not use if you have taken a MAO inhibitor (certain drugs used for depression, Parkinson disease, or other conditions) within 2 weeks.


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Epinephrine crosses the placenta (Sandler 1964). Uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia may occur. Epinephrine is recommended for the treatment of anaphylaxis in pregnant women. Specific dosing is not available; use with caution and monitor hemodynamic response (Hepner 2013). In general, medications used for ACLS in pregnant women are given at the same dose as nonpregnant patients (AHA [Vanden Hoek 2010]).


Actions


Pharmacology

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


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)


Onset of Action

Bronchodilation: Inhalation: ~1 minute


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience dizziness, anxiety, tremors, or insomnia. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), angina, tachycardia, abnormal heartbeat, severe headache, or seizures (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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