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EPHEDrine (Systemic)

Pronunciation

Pronunciation

(e FED rin)

Index Terms

  • Ephedrine Sulfate

Dosage Forms

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

Capsule, Oral, as sulfate:

Generic: 25 mg [DSC]

Solution, Injection, as sulfate:

Generic: 50 mg/mL (1 mL)

Solution, Injection, as sulfate [preservative free]:

Generic: 50 mg/mL (1 mL)

Solution, Intravenous, as sulfate:

Akovaz: 50 mg/mL (1 mL)

Brand Names: U.S.

  • Akovaz

Pharmacologic Category

  • Alpha/Beta Agonist

Pharmacology

Releases tissue stores of norepinephrine and thereby produces an alpha- and beta-adrenergic stimulation; longer-acting and less potent than epinephrine

Absorption

IV: Rapid, complete

Metabolism

Minimally hepatic; metabolites include p-hydroxyephedrine, p-hydroxynorephedrine, norephedrine

Excretion

Urine (primarily unchanged; dependent upon urinary pH with greatest excretion in acid pH)

Onset of Action

IM: Within 10 to 20 minutes.

Duration of Action

Pressor/cardiac effects: SubQ: 1 hour

Half-Life Elimination

Dependent upon urinary pH; Urine pH 5: ~3 hours; Urine pH 6.3: ~6 hours

Special Populations: Renal Function Impairment

Elimination half-life may be increased.

Use: Labeled Indications

Hypotension, anesthesia-induced: Treatment of anesthesia-induced hypotension

Note: The use of ephedrine for the treatment of acute bronchospasm, Stokes-Adams syndrome (ie, presyncope/syncope) with complete heart block, narcolepsy, depression, or myasthenia gravis has fallen out of favor given the availability of more effective agents for these conditions.

Use: Unlabeled

Postoperative nausea and vomiting (PONV) refractory to traditional antiemetics

Contraindications

Hypersensitivity to ephedrine, other sympathomimetics, or any component of the formulation; angle-closure glaucoma; coadministration with myocardial sensitizing anesthetics (cyclopropane or halothane).

Dosing: Adult

Hypotension, anesthesia-induced: IV: 5 to 25 mg/dose slow IV push; repeat as needed to maintain blood pressure (maximum total dose: 50 mg)

Postoperative nausea and vomiting (prevention) (off-label use): IM: 0.5 mg/kg at the end of surgery (Hagemann 2000; SAMBA [Gan 2007])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hypotension, anesthesia induced: Infants, Children, and Adolescents ≤15 years (off-label dose): IV: 0.1 to 0.3 mg/kg/dose slow IV push; repeat as needed to maintain blood pressure; maximum dose: 25 mg (Atchabahian 2013; Taguchi 1996).

Reconstitution

Pediatric: IV: In a pediatric hypotension trial, ephedrine doses of 0.1 mg/kg and 0.2 mg/kg were diluted to 1 mg/mL and 2 mg/mL, respectively (Taguchi 1996).

Adult:

IV: Dilute to 5 or 10 mg/mL with D5W or NS.

IM: For PONV (off-label use), dilute with NS (Hagemann 2000).

Administration

Administer diluted solution as a slow IV push. For PONV (off-label use), administer IM (Hagemann 2000; SAMBA [Gan 2007]).

Compatibility

Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D5NS, D51/2NS, D5W, D10W, D20W, sodium chloride 5%, LR, 1/2NS, NS.

Y-site administration: Incompatible with thiopental.

Storage

Store at room temperature; protect from light.

Drug Interactions

Alkalinizing Agents: May increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy

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

Atropine (Systemic): May enhance the therapeutic effect of EPHEDrine (Systemic). Monitor therapy

Benzylpenicilloyl Polylysine: Alpha-/Beta-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Consider therapy modification

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

Carbonic Anhydrase Inhibitors: May increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy

Cardiac Glycosides: EPHEDrine (Systemic) may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

CloNIDine: May enhance the therapeutic effect of EPHEDrine (Systemic). Monitor therapy

Cocaine: 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

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

Droxidopa: EPHEDrine (Systemic) may enhance the hypertensive effect of Droxidopa. 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

FentaNYL: Alpha-/Beta-Agonists (Indirect-Acting) may decrease the serum concentration of FentaNYL. Specifically, fentanyl nasal spray serum concentrations may decrease and onset of effect may be delayed. Monitor therapy

Hyaluronidase: May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Consider therapy modification

Inhalational Anesthetics: EPHEDrine (Systemic) may enhance the arrhythmogenic effect of Inhalational Anesthetics. Avoid combination

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

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

MAO Inhibitors: May enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Exceptions: Linezolid; Tedizolid. Avoid combination

Oxytocin: May enhance the hypertensive effect of EPHEDrine (Systemic). Monitor therapy

Propofol: May enhance the therapeutic effect of EPHEDrine (Systemic). Monitor therapy

Rocuronium: EPHEDrine (Systemic) may enhance the therapeutic effect of Rocuronium. 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

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 (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

Urinary Acidifying Agents: May decrease the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy

Test Interactions

Can cause a false-positive amphetamine EMIT assay

Adverse Reactions

Frequency not defined.

Cardiovascular: Angina pectoris, bradycardia, cardiac arrhythmia, hypertension, palpitations, pulse irregularity, tachycardia, ventricular ectopy, visceral vasoconstriction (renal)

Central nervous system: Anxiety, confusion, delirium, dizziness, hallucination, headache, insomnia, intracranial hemorrhage, nervousness, precordial pain, restlessness, tension, vertigo

Dermatologic: Diaphoresis, pallor

Gastrointestinal: Anorexia, nausea, vomiting

Genitourinary: Dysuria, oliguria, urinary retention (males with prostatism)

Neuromuscular & skeletal: Tremor, vesicle sphincter spasm, weakness

Respiratory: Dyspnea

Miscellaneous: Tachyphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: May cause hypertension resulting in intracranial hemorrhage. May also induce anginal pain in patients with coronary insufficiency or ischemic heart disease and induce potentially fatal arrhythmias in patients with heart disease or who are receiving drugs that sensitize the myocardium.

• Urine output: Constriction of renal blood vessels may occur, decreasing urine output.

Disease-related concerns:

• Cardiovascular disease: Ephedrine should not ordinarily be used where vasopressor drugs may be contraindicated, such as hypertension and other cardiovascular disorders (eg angina pectoris, coronary artery disease, arrhythmias); use with caution.

• Diabetes: Ephedrine should not ordinarily be used in cases where vasopressor drugs may be contraindicated, such as diabetes; use with caution.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Renal impairment: Use with caution in patients with renal impairment; increased elimination half-life may occur. Carefully monitor patients with renal impairment for adverse reactions.

• Thyroid dysfunction: Ephedrine should not ordinarily be used where vasopressor drugs may be contraindicated, such as thyrotoxicosis. Use with caution in patients with thyroid dysfunction.

• Vasomotor symptoms: Use with caution in patients with unstable vasomotor symptoms.

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.

Special populations:

• Elderly: Use with caution in the elderly.

Dosage form specific issues:

• Injectable: Blood volume depletion should be corrected before IV therapy is instituted.

Other warnings/precautions:

• Bronchodilator use: Avoid as a bronchodilator; ephedrine is generally not used as a bronchodilator since other beta2 agonists are less toxic.

• Long-term use: Prolonged use may cause anxiety and symptoms of paranoid schizophrenia (eg, tachycardia, poor nutrition and hygiene, fever, cold sweat and dilated pupils).

• Tolerance: Tachyphylaxis and tolerance may develop with repeated, prolonged, or excessive administration; temporary cessation of therapy restores its effectiveness.

Monitoring Parameters

Blood pressure, pulse, respiratory symptoms; monitor patients with renal impairment for adverse reactions.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Ephedrine crosses the placenta (Hughes, 1985). Ephedrine injection is used at delivery for the prevention and/or treatment of maternal hypotension associated with spinal anesthesia in women undergoing cesarean section (ASA, 2007). Serious postpartum hypertension and possibly stroke may occur if administered with oxytocic medications. Metabolic acidosis has been reported in neonates following maternal use of ephedrine; monitor.

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 tremors, insomnia, nausea, vomiting, lack of appetite, or headache. Have patient report immediately to prescriber severe headache, vision changes, angina, tachycardia, abnormal heartbeat, severe dizziness, passing out, severe anxiety, or urinary retention (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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