Racemic epinephrine

Administration

• Type: Sympathomimetic (nonselective alpha- and beta-adrenergic agonist)
• Dosage Forms: Inhalation solution 2.25% (racepinephrine HCl); available as 0.5 mL unit-dose vials
• Routes of Administration: Nebulization (oral inhalation only)
• Common Trade Names: AsthmaNefrin, S2

Adult Dosing

• Asthma/Bronchospasm:
  • S2: 0.5 mL of 2.25% solution diluted in 3 mL normal saline (NS) via jet nebulizer every 3-4 hours as needed
  • AsthmaNefrin: 1-3 inhalations of 0.5 mL of 2.25% solution via EZ Breathe Atomizer; max 12 inhalations/24 hours
• Croup/Stridor/Laryngeal edema:
  • 0.5 mL of 2.25% solution diluted in 3 mL NS via jet nebulizer over 15 minutes; may repeat every 20 minutes as needed
• Post-extubation stridor:
  • 0.5 mL of 2.25% solution diluted in 3 mL NS via jet nebulizer; may repeat every 20 minutes as needed
• Alternative if racemic epi unavailable: L-epinephrine 1 mg/mL (1:1000): 5 mL undiluted via nebulizer

Pediatric Dosing

• <4 years:
  • 0.05 mL/kg of 2.25% solution via jet nebulizer diluted in 3 mL NS over 15 minutes; max 0.5 mL/dose
  • Croup: every 2 hours (with heart rate monitoring); asthma: no more often than every 12 hours
  • Use low end of dosing range for younger infants
• ≥4 years:
  • 0.5 mL of 2.25% solution via jet nebulizer diluted in 3 mL NS over 15 minutes every 3-4 hours as needed
• Alternative if racemic epi unavailable: L-epinephrine 1 mg/mL: 3 mL for <10 kg; 5 mL for ≥10 kg (undiluted)

Special Populations

Pregnancy Rating

• Category C (former FDA system); FDA has not assigned a category under the current labeling rule
• No well-controlled studies in humans; animal studies show evidence of fetal harm
• Epinephrine crosses the placenta; use only if benefits outweigh risks

Lactation risk

• Systemic epinephrine is excreted in breast milk
• No data on whether inhaled racemic epinephrine is present in breast milk
• Due to poor oral bioavailability and short half-life, unlikely to significantly affect the nursing infant
• Use with caution

Renal Dosing

• Adult: No specific dosage adjustments recommended; use with caution and monitor
• Pediatric: No specific dosage adjustments recommended

Hepatic Dosing

• Adult: No specific dosage adjustments recommended
• Pediatric: No specific dosage adjustments recommended

Contraindications

• Allergy to class/drug
• Epiglottitis
• Concurrent use of MAOIs or within 2 weeks of discontinuing an MAOI
• Use caution with:
  • Heart disease
  • Hypertension
  • Thyroid disease (hyperthyroidism)
  • Diabetes
  • Urinary retention caused by prostatic hypertrophy
  • Closed-angle glaucoma
  • Ventricular outflow tract obstruction (e.g., tetralogy of Fallot)
  • Geriatric or cardiac patients

Adverse Reactions

Serious

• Cardiac arrhythmias (tachyarrhythmias)
• Severe hypertension
• Pulmonary edema
• Cerebrovascular hemorrhage (in overdose)
• Rebound/re-emergence of airway edema (typically 1-3 hours post-dose)
• Anginal pain
• Subarachnoid hemorrhage

Common

• Tachycardia
• Hypertension
• Headache
• Tremor
• Restlessness/agitation
• Nausea and vomiting
• Sweating
• Pallor
• Dizziness
• Hyperglycemia

Pharmacology

• Half-life: <5 minutes (plasma)
• Metabolism: Hepatic (and other extraneuronal tissues) via catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO); primary metabolites include metanephrine and vanillylmandelic acid (VMA)
• Excretion: Renal (primarily as inactive metabolites; negligible unchanged drug in urine)
• Onset of action: 1-5 minutes
• Duration of action: 1-3 hours
• Systemic bioavailability via inhalation: <10%

Mechanism of Action

• Racemic epinephrine is a 1:1 mixture of the d- (S+) and l- (R−) isomers of epinephrine
• Nonselective agonist at alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors (all G-protein-coupled receptors)
• Alpha-1 mediated vasoconstriction: constricts submucosal arterioles → reduces mucosal edema and capillary leakage (primary effect in croup/stridor; onset within 10-15 minutes)
• Beta-2 mediated bronchodilation: relaxes bronchial smooth muscle → relieves bronchospasm, wheezing, chest tightness (primary therapeutic effect in asthma)
• Beta-2 agonism activates adenylyl cyclase → increases intracellular cyclic AMP

Comments

• Observe patients for at least 4-6 hours after administration due to risk of rebound worsening of airway edema
• Rebound phenomenon is likely a re-emergence of symptoms as medication wears off, rather than true rebound
• Monitor cardiac rate and rhythm with continuous ECG during administration
• Co-administration of corticosteroids (e.g., dexamethasone) reduces likelihood of symptom recurrence
• L-epinephrine alone is considered equally efficacious as racemic epinephrine for croup and post-extubation stridor
• Not indicated as first-line therapy for routine asthma management
• Discard solution if brown, cloudy, pinkish, or darker than slightly yellow

See Also

• Croup
• Stridor
• Post-extubation stridor
• Epinephrine
• Asthma