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EPHEDrine (Systemic)


General


Pronunciation

(e FED rin)


Brand Names: U.S.

  • Akovaz

Indications


Use: Labeled Indications

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, or depression has fallen out of favor given the availability of more effective agents for these conditions.


Contraindications


Hypersensitivity to ephedrine or any component of the formulation; angle-closure glaucoma; concurrent use of other sympathomimetic agents


Dosing and Administration


Dosing: Adult

Hypotension induced by anesthesia: IV: 5 to 25 mg/dose slow IV push repeated after 5 to 10 minutes as needed to maintain blood pressure

Idiopathic orthostatic hypotension (off-label use): Oral: 25 to 50 mg 3 times daily; maximum: 150 mg daily. Note: Not considered first-line for this indication.

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


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Hypotension induced by anesthesia: IV:

Infants, Children, and Adolescents ≤15 years (off-label dose): 0.1 to 0.2 mg/kg/dose slow IV push; administer as needed to maintain blood pressure; maximum: 25 mg (Taguchi, 1996)

Adolescents >15 years: Refer to adult dosing


Reconstitution

Injection solution: dilute to 5 or 10 mg/mL.


Administration

Injection solution: Administer diluted solution as a slow IV push. Do not administer unless solution is clear.


Storage

Protect all dosage forms from light.

Injection solution: Store at room temperature. Note: Storage guidelines vary; check product labeling for exact temperature range.


Dosage Forms/Strengths


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)


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.


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 patients 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

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


Monitoring Parameters

Injection solution: Monitor blood pressure, pulse


Lab Test Interferences


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:

- Hypertension: May cause hypertension.

- Psychiatric disorders: Long-term use may cause anxiety and symptoms of paranoid schizophrenia.

Disease-related concerns:

- Cardiovascular disease: Use with caution in patients with cardiovascular disease such as coronary artery disease, arrhythmias, and hypertension.

- Diabetes: Use with caution in patients with diabetes mellitus.

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

- Seizures: Use with caution in patients with a history of seizure disorder.

- Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

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

Concurrent drug therapy issues:

- Monoamine oxidase inhibitors (MAO-I): Use with extreme caution in patients taking MAO inhibitors; prolonged hypertension may result from concurrent use.

Special populations:

- Elderly: Use with caution in the elderly, since it crosses the blood-brain barrier and may cause confusion.

Dosage form specific issues:

- Injectable: Blood volume depletion should be corrected before IV/IM 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: May cause anxiety and symptoms of paranoid schizophrenia.


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).


Actions


Pharmacology

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


Absorption

Oral: Complete


Metabolism

Minimally hepatic by oxidative deamination, demethylation, aromatic hydroxylation, and conjugation; metabolites include p-hydroxyephedrine, p-hydroxynorephedrine, norephedrine


Excretion

Dependent upon urinary pH with greatest excretion in acid pH; Urine pH 5: 74% to 99% excreted unchanged; urine pH 8: 22% to 25% excreted unchanged


Duration of Action

Pressor/cardiac effects: Oral: 3 to 6 hours; SubQ: 1 hour


Half-Life Elimination

2.5 to 3.6 hours


Patient and Family Education


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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