Version July 2025
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.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral inhalation: No dosage adjustment likely to be necessary for any degree of kidney impairment (limited excretion in urine as unchanged drug) (Ref).
Hemodialysis, intermittent (thrice weekly): Oral inhalation: Not significantly dialyzed (Ref): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Oral inhalation: No dosage adjustment necessary (Ref).
CRRT: Oral inhalation: Unlikely to be significantly dialyzable (Ref): No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral inhalation: No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Epinephrine (adrenaline) (oral inhalation): Pediatric drug information")
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, moderate to severe: Limited data available: Note: Symptom improvement usually occurs within 10 to 30 minutes and lasts 2 to 3 hours; patients should be observed for 2 to 3 hours after initial treatment for symptom recurrence and possible need for repeat treatment (Ref).
Infants and Children:
Racemic epinephrine (2.25% inhalation solution): Nebulization: 0.05 to 0.1 mL/kg (maximum dose: 0.5 mL/dose) diluted in 2 to 3 mL NS, may repeat dose every 15 to 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 (maximum dose: 5 mL/dose) diluted in NS, may repeat dose every 15 to 20 minutes; Note: 5 mL of L-epinephrine (1 mg/mL) is equivalent to 0.5 mL of 2.25% racemic epinephrine (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no adverse reactions listed in the manufacturer's labeling.
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.
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.
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]
No
Nebulization (Asthmanefrin Refill Inhalation)
2.25% (per each): $2.50
Nebulization (S2 (Racepinephrine) Inhalation)
2.25% (per each): $2.50
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Nebulization Solution, Inhalation:
S2 (Racepinephrine): 2.25% ([DSC])
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.
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.
Asthma, mild intermittent 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; clinical practice guidelines do not recommend nonselective beta agonists (eg, epinephrine) for routine management and treatment of asthma due to their potential for excessive cardiac stimulation, especially in high doses (GINA 2024; NAEPP 2007).
EPINEPHrine may be confused with ePHEDrine
Substrate of COMT;
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.
Alpha1-Blockers: May decrease therapeutic effects of Alpha-/Beta-Agonists. Risk C: Monitor
Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Beta-Blockers (Beta1 Selective): May decrease therapeutic effects of EPINEPHrine (Oral Inhalation). Risk C: Monitor
Beta-Blockers (Nonselective): May increase hypertensive effects of EPINEPHrine (Oral Inhalation). Risk C: Monitor
Beta-Blockers (with Alpha-Blocking Properties): May decrease therapeutic effects of EPINEPHrine (Oral Inhalation). Risk C: Monitor
Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Bromocriptine: May increase hypertensive effects 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 increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Chloroprocaine (Systemic): May increase hypertensive effects of Alpha-/Beta-Agonists. Risk C: Monitor
Cocaine (Topical): May increase hypertensive effects 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 serum concentration of COMT Substrates. Risk C: Monitor
Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor
Doxofylline: Sympathomimetics may increase adverse/toxic effects of Doxofylline. Risk C: Monitor
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May increase vasoconstricting effects of Alpha-/Beta-Agonists. Risk X: Avoid
Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor
Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor
Hexoprenaline: May increase adverse/toxic effects of Alpha-/Beta-Agonists. Risk X: Avoid
Inhalational Anesthetics: May increase arrhythmogenic effects of EPINEPHrine (Oral Inhalation). Risk C: Monitor
Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid
Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor
Lisuride: May increase hypertensive effects of Alpha-/Beta-Agonists. Risk X: Avoid
Monoamine Oxidase Inhibitors: May increase hypertensive effects of EPINEPHrine (Oral Inhalation). Risk X: Avoid
Pergolide: May increase hypertensive effects of Alpha-/Beta-Agonists. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May increase tachycardic effects of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitor may increase vasopressor effects 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 increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Spironolactone: May decrease vasoconstricting effects of Alpha-/Beta-Agonists. Risk C: Monitor
Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor
Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor
Tricyclic Antidepressants: May increase vasopressor effects 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
Avoid food or beverages that contain caffeine.
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 every 4 to 6 weeks during pregnancy. However, epinephrine inhalation is not recommended for routine management and treatment of asthma (ERS/TSANZ [Middleton 2020]; GINA 2024).
Use of epinephrine is generally considered acceptable with breastfeeding (WHO 2002).
Avoid food or beverages that contain caffeine.
FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium; asthma symptoms
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
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)
