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Ephedrine (Monograph)

Brand name: Akovaz
Drug class: alpha- and beta-Adrenergic Agonists
VA class: AU100
Chemical name: [R-(R*, S*)]-α-[1-(Methylamino)ethyl]-benzenemethanol hydrochloride
Molecular formula: C10H15NO • HCl(C10H15NO)2 • H2SO4
CAS number: 299-42-3

Medically reviewed by Drugs.com on May 6, 2024. Written by ASHP.

Introduction

Sympathomimetic agent.a

Uses for Ephedrine

Hypotension During Anesthesia

Used parenterally for treatment of clinically important hypotension in the setting of anesthesia.178 200 247 249 250 251 252 255

Increases systolic and mean arterial BP when administered as a direct IV (“bolus”) injection following development of hypotension in patients receiving neuraxial and/or general anesthesia.178 200 252 Such effects observed across a variety of surgical settings, including obstetric surgery in pregnant women undergoing cesarean delivery with neuraxial anesthesia.200 252

Although ephedrine historically considered the vasopressor of choice in obstetric anesthesia, some evidence suggests that phenylephrine may provide more favorable fetal acid-base balance.247 248 249 250 251 255 Experts currently recommend either IV ephedrine or phenylephrine for treatment of hypotension during neuraxial anesthesia; however, consideration should be given to selection of phenylephrine in the absence of maternal bradycardia because of improved fetal acid-base status in uncomplicated pregnancies.255

IM use of ephedrine also evaluated in this setting; however, results have been equivocal.255

Bronchospasm

Used orally as a bronchodilator for symptomatic treatment of asthma.176 198 220 221 222

Used in fixed-combination with guaifenesin as self-medication for the temporary relief of mild symptoms of intermittent asthma (e.g., wheezing, chest tightness, shortness of breath).176 198 199

Use of an OTC bronchodilator may be appropriate in patients with mild symptoms of intermittent asthma; however, those with more severe asthma (i.e., persistent asthma) or worsening asthma (symptoms not relieved within 60 minutes or with maximum recommended dosages, increasing frequency of asthma attacks) should consult a clinician for other treatment options.199

While oral ephedrine was once widely used in the treatment of asthma,221 224 the drug generally has been replaced by more selective and rapid-acting agents (e.g., inhaled β2-adrenergic agonists).176 198 199 223 224 225

CNS Conditions

Has been used in the treatment of narcolepsy† [off-label] or depressive states† [off-label]; however, cardiovascular effects of the drug limit usefulness in these conditions.a

Obesity

Previously used for self-medication in the management of obesity† [off-label].181 184 185

Dietary supplements containing ephedrine alkaloids are no longer commercially available in the US.189 (See Risks Associated with Dietary Supplements under Cautions.)

Nasal Congestion

Has been used as a nasal decongestant, but of doubtful value when used for this condition.a

Myasthenia Gravis

Has been used in patients with myasthenia gravis† [off-label]; however, randomized controlled studies are needed to evaluate potential benefit.178 226

Misuse and Abuse

Has been misused and abused by athletes, bodybuilders, weight lifters, and others, including high school- and college-aged individuals engaged in sports† [off-label].181

Dietary supplements containing ephedrine alkaloids are no longer commercially available in the US.189 (See Risks Associated with Dietary Supplements under Cautions.)

Ephedrine has been used in clandestine synthesis of methamphetamine and methcathinone.a Federal restrictions to reduce the potential for misuse (diversion) and abuse of ephedrine include limiting the amount that can be purchased to 3.6 g per day or 9 g per month, requiring storage behind the counter or in a locked cabinet, requiring purchasers to provide approved photographic identification, and requiring retail distributors to maintain a written or electronic logbook of purchases for at least 2 years.204 205 209 210 211 (For additional information on these and other federal restrictions, visit [[Web]]).212 213 214 Additional requirements have been enacted in some states;102 104 106 109 202 203 206 follow state requirements if such requirements are more stringent than federal restrictions.209 212 213

Ephedrine Dosage and Administration

Administration

Oral Administration

Administer orally as a fixed-combination preparation.176 177 198

Parenteral Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV injection.178 200 Also has been administered by sub-Q† or IM† injection.178

Administer ephedrine sulfate (Akovaz) by direct IV (“bolus”) injection.200 252 Must dilute commercially available injection prior to IV administration.200 May prepare a 5-mg/mL solution by diluting 1 mL of the 50-mg/mL injection concentrate with 9 mL of 0.9% sodium chloride injection or 5% dextrose injection.200

Vials are for single-use only; discard unused portions.200

Dosage

Available as ephedrine hydrochloride or ephedrine sulfate; dosage expressed in terms of the salt.176 178 198 200

Pediatric Patients

Hypotension During Anesthesia
IM† or Sub-Q†

Ephedrine sulfate: Usual dose of 0.5 mg/kg or 16.7 mg/m2 every 4–6 hours has been administered.178 However, ephedrine sulfate injection not FDA-labeled for use in pediatric patients.200 252

Bronchospasm
Oral

Ephedrine hydrochloride or sulfate self-medication in children ≥12 years of age: 12.5–25 mg every 4 hours as needed for treatment of mild symptoms of intermittent asthma; administer in fixed combination with guaifenesin.176 198

IM† or Sub-Q†

Ephedrine sulfate: Usual dose of 0.5 mg/kg or 16.7 mg/m2 every 4–6 hours has been administered.178 However, ephedrine sulfate injection not FDA-labeled for use in pediatric patients.200 252

Adults

Hypotension During Anesthesia
IV

Ephedrine sulfate: Initially, 5–10 mg by IV bolus injection; administer additional bolus doses as needed (up to a total dose of 50 mg) to achieve desired BP response.200

Other IV dosage regimens have been recommended.178 250

IM † or Sub-Q†

Ephedrine sulfate: Usual dose of 25–50 mg has been administered.178

Bronchospasm
Oral

Ephedrine hydrochloride or sulfate self-medication: 12.5–25 mg every 4 hours as needed for treatment of mild symptoms of intermittent asthma; administer in fixed combination with guaifenesin.176 198

Parenteral

Ephedrine sulfate: Parenteral doses of 12.5–25 mg have been given.a

Prescribing Limits

Pediatric Patients

Bronchospasm
Oral

Ephedrine hydrochloride or sulfate self-medication in children ≥12 years of age: Maximum 150 mg in any 24-hour period.176 198

Adults

Bronchospasm
Oral

Ephedrine hydrochloride or sulfate self-medication: Maximum 150 mg in any 24-hour period.176 198

Detailed Ephedrine dosage information

Cautions for Ephedrine

Contraindications

Warnings/Precautions

Warnings

Cardiovascular Effects

May cause hypertension and tachycardia; risk of serious adverse effects (e.g., MI, stroke, intracranial hemorrhage, exacerbation of CHF, death).178 189 200 (See Risks Associated with Dietary Supplements under Cautions.)

Serious postpartum hypertension, in some cases resulting in stroke, reported in patients receiving a vasopressor (e.g., ephedrine) and an oxytocic agent (e.g., ergonovine, methylergonovine) concomitantly.200 (See Specific Drugs under Interactions.)

Increased risk of hypertension in patients receiving ephedrine sulfate injection for prevention of hypotension.200

Risk of anginal pain in patients with coronary insufficiency or ischemic heart disease.a Risk of potentially fatal arrhythmias in patients with organic heart disease or in those receiving drugs that sensitize the myocardium (e.g., cyclopropane, halothane).a

Caution in patients with cardiovascular disease (e.g., angina) and in those receiving digoxin.178

Tolerance and Tachyphylaxis

Tolerance and tachyphylaxis may develop with repeated parenteral administration; in some cases; effectiveness may return after the drug is withheld temporarily.178 200

If used for treatment of hypotension during anesthesia, consider possibility of tachyphylaxis and be prepared to use an alternative vasopressor.200

Concomitant Diseases

Use with caution in patients with cardiovascular disease, hypertension, angina, hyperthyroidism, diabetes mellitus, or prostatic hyperplasia.178 Patients with cardiovascular disease, hypertension, diabetes mellitus, thyroid disease, seizures, angle-closure (narrow-angle) glaucoma, psychiatric or emotional conditions should consult a clinician before initiating self-medication with ephedrine.176 198

Use for self-medication for bronchospasm only if previously diagnosed with asthma; do not use if previously hospitalized for asthma unless directed by a clinician.176 198

Risks Associated with Dietary Supplements

Dietary supplements containing ephedrine alkaloids have been associated with serious adverse cardiac effects (e.g., hypertension, possibly resulting in MI, stroke, or death),189 CNS effects, and death.113 114 115 117 118 120 131 134 144 160 172 181 183

In February 2004, FDA declared dietary supplements containing ephedrine alkaloids adulterated by virtue of their unreasonable health risks to consumers.189 Manufacturing, sale, and distribution of all dietary supplements containing ephedrine alkaloids (e.g., Ephedra spp. [“ma huang”], Sida cordifolia, Pinellia spp.) were prohibited after April 12, 2004.189 190 This regulation does not apply to traditional Chinese herbal remedies or products regulated as conventional foods (e.g., herbal teas).190 Ephedra is not generally recognized as safe for foods and not approved for use as a food additive.190 After litigation, FDA’s rule was upheld, and FDA reiterated its position that no dosage of dietary supplements containing ephedrine alkaloids is safe, and the sale of these products in the US is illegal and subject to FDA enforcement action.195 196 197 201 207 208

General Precautions

When used in fixed combination with guaifenesin, observe the usual cautions, precautions, and contraindications associated with guaifenesin.176 177 198

Duration of Therapy

Self-medication in asthma: Consult a clinician if symptoms are not improved within 1 hour or worsen, more than the recommended dosage of ephedrine is required, or asthma attacks become more frequent (i.e., >2 asthma attacks in a week).176 198

Misuse and Abuse

Potential for misuse and abuse.a

Specific Populations

Pregnancy

Animal reproduction studies not performed to date; not known whether the drug can cause fetal harm or miscarriage when administered during pregnancy.178 200 252

Has been used in pregnant women for treatment of hypotension during spinal anesthesia; available data support efficacy and safety of ephedrine sulfate injection for such use.253 254

Some evidence indicates that fetal acidosis is more likely to occur with ephedrine than phenylephrine.252 Low umbilical artery pH (≤7.2) reported at the time of delivery in neonates whose mothers were exposed to ephedrine.200 Assess acid-base status in newborn infants and monitor for signs and symptoms of metabolic acidosis.200

Lactation

Distributed into milk; however, no information regarding effects on breast-fed infant or milk production.178 200 Consider known benefits of breast-feeding along with mother's clinical need for ephedrine and any potential adverse effects of the drug or underlying maternal condition on the infant.200

Pediatric Use

Ephedrine sulfate injection is not FDA-labeled for use in pediatric patients.200 252 Although the drug has been used in children,178 safety and efficacy not established in this patient population.200

Should not be used for self-medication in children <12 years of age unless otherwise directed by a clinician.177 198

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.215 216 Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established.215 Therefore, FDA recommends not to use such preparations in children <2 years of age;c safety and efficacy in older children under evaluation.e g Because children 2–3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age.d e f g FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns.d e f Clinicians should ask caregivers about use of OTC cough/cold preparations to avoid overdosage.b

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.200 Other clinical experience has not identified differences in responses between geriatric and younger patients.200 Select dosage with caution, usually starting at low end of dosage range.200

Because geriatric patients may have decreased renal function, risk of adverse effects may be increased; consider monitoring renal function.200

Renal Impairment

Substantially excreted by kidneys; risk of ephedrine-induced adverse effects may be increased in patients with impaired renal function.200

Carefully monitor patients with renal impairment after administration of initial IV dose.200

Common Adverse Effects

Parenteral ephedrine: Nervousness, insomnia, vertigo, headache, tachycardia, palpitation, sweating, nausea, vomiting, anorexia, vesical sphincter spasm (resulting in difficult and painful urination), urinary retention (particularly in males with prostatism).178 200

Drug Interactions

Specific Drugs

Drug

Interaction

Comment

α-Adrenergic blocking agents

Vasopressor response to ephedrine decreaseda

Carefully monitor BP200

β-Adrenergic blocking agents

Antagonism of cardiac and bronchodilating effects of ephedrinea

Carefully monitor BP200

Anesthetics, epidural

May decrease efficacy of epidural blockade by facilitating regression of sensory analgesia200

Monitor patients for this effect and treat accordingly200

Anesthetics, general (e.g., halogenated hydrocarbons [e.g., halothane], cyclopropane)

Increased cardiosensitivity to ephedrine and possible increased risk of arrhythmias178

Atropine

May increase pressor effect200

Carefully monitor BP200

Cardiac glycosides

Increased cardiosensitivity to ephedrine and possible increased risk of arrhythmias178 200

Carefully monitor patients 178 200

Clonidine

May increase pressor effect200

Carefully monitor BP200

Diuretics

Decreased arterial responsiveness to pressor drugsa

MAO inhibitors

Pressor effects of ephedrine increased; may result in hypertensive crisis or subarachnoid hemorrhage rarelya

Carefully monitor BP200

Some manufacturers recommend avoidance with or for 2 weeks after discontinuance of MAO inhibitors176 178

Oxytocics (e.g., ergonovine, methylergonovine)

May increase pressor effect and cause severe postpartum hypertension and possible stroke178 200

Carefully monitor BP200

Propofol

May increase pressor effect200

Carefully monitor BP200

Quinidine

May antagonize pressor effect200

Carefully monitor BP200

Reserpine

May antagonize pressor effect200

Carefully monitor BP200

Rocuronium

Ephedrine may reduce onset time of rocuronium-induced neuromuscular blockade for intubation when administered simultaneously with anesthetic induction200

Theophylline

May increase incidence of nausea, nervousness, and insomnia200

Monitor patients for these symptoms and treat accordingly200
Ephedrine drug interactions (more detail)

Ephedrine Pharmacokinetics

Absorption

Bioavailability

Peak serum concentrations attained within 2.6–3 hours following oral administration.120

Onset

Oral administration: Bronchodilation occurs within 15–60 minutes.a

Duration

Oral administration: Bronchodilation persists for 2–4 hours; pressor and cardiac responses persist for up to 4 hours following oral administration of 15–50 mg.a

Parenteral administration: Pressor and cardiac responses persist for 1 hour after IV administration of 10–25 mg or IM or sub-Q administration of 25–50 mg.a

Distribution

Extent

Distributed into milk.178 200

Elimination

Metabolism

Metabolic pathway not completely elucidated.200 253 Some data suggest drug is slowly metabolized in the liver.a

Elimination Route

Ephedrine and its metabolites are excreted in urine; most of the drug is excreted as unchanged ephedrine.a The rate of urinary excretion of ephedrine and its metabolites is dependent upon urinary pH.a

Half-life

About 3 hours when the urine is acidified to pH 5; about 6 hours when urinary pH is about 6.3.a

Stability

Storage

Oral

Fixed-dose Combination with Guaifenesin

Primatene tablets: 20–25°C.176

Bronkaid caplets: Room temperature; avoid exposure to >40°C.198

Parenteral

Injection

20–25°C.178 200 Store in carton until time of use.200 Protect from light.178

Compatibility

Parenteral

Solution CompatibilityHID

Compatible

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose–saline combinations

Dextrose 2½, 5, or 10% in water

Ionosol products

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M
Drug Compatibility
Admixture CompatibilityHID

Compatible

Chloramphenicol sodium succinate

Lidocaine HCl

Nafcillin sodium

Penicillin G potassium

Incompatible

Pentobarbital sodium

Phenobarbital sodium
Y-site CompatibilityHID

Compatible

Bivalirudin

Dexmedetomidine HCl

Etomidate

Fenoldopam mesylate

Hetastarch in lactated electrolyte injection (Hextend)

Propofol

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

ePHEDrine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

ePHEDrine Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

50 mg/mL*

Akovaz

Eclat

ePHEDrine Sulfate Injection
ePHEDrine Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

12.5 mg with Guaifenesin 200 mg

Ephed Plus

DMD

Primatene

Pfizer

25 mg with Guaifenesin 200 mg

Ephed Plus

DMD
ePHEDrine Sulfate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg with Guaifenesin 400 mg

Bronkaid Caplets

Bayer

AHFS DI Essentials™. © Copyright 2025, Selected Revisions May 15, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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