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]
Pharmacology
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/Pharmacodynamics
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: Not recommended for routine management and treatment of asthma (GINA 2018; 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.
Dosage and Administration
Dosing: Adult
Bronchospasm, relief of mild asthma symptoms: Note: Not recommended for routine management and treatment of asthma (GINA 2018; 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 at least 3 hours as needed (maximum dose: 12 inhalations/24 hours).
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)
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). Exceptions: Arotinolol; Carvedilol; Labetalol. 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. Exceptions: Cannabidiol. 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 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
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
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
Solriamfetol: Sympathomimetics may enhance the hypertensive 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.
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.
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
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). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications (ACOG 90 2008; GINA 2018; NAEPP 2007). Epinephrine is not recommended for routine management and treatment of asthma (GINA 2018; NAEPP 2007).
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.
Frequently reported side effects of this drug
- Tremors
- Trouble sleeping
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes.
- Chest pain
- Fast heartbeat
- Abnormal heartbeat
- Vision changes
- Passing out
- Anxiety
- Severe headache
- Dizziness
- Seizures
- Signs of a significant reaction like 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. 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
