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EPINEPHrine (Oral Inhalation)

Medically reviewed by Drugs.com. Last updated on Jul 11, 2020.

Pronunciation

(ep i NEF rin)

Index Terms

  • Primatene Mist
  • Racemic Epinephrine
  • Racepinephrine
  • Racepinephrine HCL

Dosage Forms

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]

Brand Names: U.S.

  • Asthmanefrin Refill [OTC]
  • S2 (Racepinephrine) [OTC]

Pharmacologic Category

  • Alpha/Beta Agonist

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

Use: Labeled Indications

Bronchospasm, relief of mild asthma symptoms: Temporary relief of mild symptoms of intermittent asthma (ie, shortness of breath, tightness of chest, wheezing). Note: Primary utility is in acute anaphylaxis with edema; not recommended for routine management and treatment of asthma (GINA 2020; NAEPP 2007).

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.

Documentation of allergenic cross-reactivity for sympathomimetics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Bronchospasm, relief of mild asthma symptoms: Note: Primary utility is in acute anaphylaxis with edema; not recommended for routine management and treatment of asthma (GINA 2020; NAEPP 2007).

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/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/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: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Bronchospasm, relief of mild asthma symptoms: Note: Not recommended for routine management and treatment of asthma (GINA 2018; NAEPP 2007).

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 (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 (Hegenbarth 2008; Kliegman 2016; Rosekrans 1998; Rotta 2003; Wright 2002)

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 (Hegenbarth 2008)

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

Reconstitution

Nebulization solution: Dilute in 2 to 3 mL NS in the treatment of croup (Hegenbarth 2008; Kliegman 2015; Rosekrans 1998).

Administration

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 by running water through the mouthpiece for 30 seconds.

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

Dietary Considerations

Avoid food or beverages that contain caffeine.

Storage

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.

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 (Beta1 Selective): May diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Monitor therapy

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

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

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

Chloroprocaine: May enhance the hypertensive effect of Alpha-/Beta-Agonists. 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. Consider therapy modification

COMT Inhibitors: May increase the serum concentration 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. Avoid combination

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

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

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

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Consider therapy modification

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. 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). Consider therapy modification

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

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

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

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. 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. Consider therapy modification

Adverse Reactions

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

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.

Monitoring Parameters

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

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 2020).

Patient Education

What is this drug used for?

• It is used to treat asthma.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Tremors

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Vision changes

• Passing out

• Anxiety

• Severe headache

• Dizziness

• Seizures

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions