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Ephedrine Hydrochloride

Pronunciation

Class: alpha- and beta-Adrenergic Agonists
Note: This monograph also contains information on Ephedrine, Ephedrine Sulfate
VA Class: AU100
CAS Number: 299-42-3

Introduction

Sympathomimetic agent.a

Uses for Ephedrine Hydrochloride

Bronchospasm

Used orally as a bronchodilator to relieve shortness of breath, chest tightness, wheezing, and cough associated with bronchial asthma.176 198 200 Improves cough symptoms associated with the common cold, bronchial asthma, or bronchitis.177

Administered parenterally for the relief of acute bronchospasm; less effective than epinephrine.199

Hypotension

Has been used both for the prevention and treatment of hypotension resulting from spinal anesthesia or other types of nontopical conduction anesthesia.175 199

Routine prophylactic use of any vasopressor in spinal anesthesia has been questioned because hypotension does not always occur during spinal anesthesia and treatment can readily be instituted if necessary; it has been suggested that vasopressors be administered prophylactically only in those cases in which a substantial decrease in BP is expected.a

Use of vasopressors to correct hypotension occurring during anesthesia in obstetrical patients is controversial; hypotension can usually be minimized by adequate hydration and changing the position of the patient so that the uterus does not compress the inferior vena cava; if a vasopressor is required, ephedrine is usually preferred.a

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May be used to treat hypotension following sympathectomy or overdosage of certain drugs (adrenergic and ganglionic blocking agents, veratrum alkaloids, other antihypertensive agents).a

Cardiac Arrhythmias and Heart Block

Management of Adams-Stokes syndrome with complete heart block.175 Electrical cardiac pacemakers have largely replaced drug therapy in third-degree AV block (complete heart block).a

CNS Conditions

Treatment of narcolepsy or depressive states;175 the cardiovascular effects limit usefulness in these conditions.a

Obesity

Previously used for self-medication in the management of obesity.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 but of doubtful value when administered orally.a

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.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 []).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 Hydrochloride Dosage and Administration

Administration

Administer orally, IV, IM, or sub-Q.175 176 177 178 198

Administer IV when an immediate effect is desired.199

Absorption and onset of action more rapid following IM administration (within 10–20 minutes) than following sub-Q administration.199

Oral Administration

Administer orally as a combination preparation.176 177 198

IV Administration

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

Administer slowly.175

Dosage

Available as ephedrine hydrochloride, ephedrine sulfate, or ephedrine tannate; dosage expressed in terms of the salt.175 176 177 198 199

Pediatric Patients

Bronchospasm
Oral

Ephedrine tannate: Children 2–6 years of age: 2.5–5 mg every 12 hours as needed; administered in fixed combination with other drugs (Rynatuss).177

Ephedrine tannate: Children >6 years of age: 5–10 mg every 12 hours as needed; administered in fixed combination with other drugs (Rynatuss).177

Ephedrine hydrochloride or sulfate self-medication in children ≥12 years of age: 12.5–25 mg every 4 hours as needed; administered in fixed combination with guaifenesin.176 198 200

IV

Ephedrine sulfate: 0.75 mg/kg or 25 mg/m2 4 times daily or as otherwise determined by patient’s response.199

IM

Ephedrine sulfate: 0.5 mg/kg or 16.7 mg/m2 every 4–6 hours.175

Sub-Q

Ephedrine sulfate: 0.5 mg/kg or 16.7 mg/m2 every 4–6 hours;175 alternatively, 0.75 mg/kg or 25 mg/m2 4 times daily or as otherwise determined by patient’s response.199

Hypotension
IV

Ephedrine sulfate: 0.75 mg/kg or 25 mg/m2 4 times daily or as otherwise determined by BP response.199

IM

Ephedrine sulfate: 0.5 mg/kg or 16.7 mg/m2 every 4–6 hours.175

Sub-Q

Ephedrine sulfate: 0.5 mg/kg or 16.7 mg/m2 every 4–6 hours;175 alternatively, 0.75 mg/kg or 25 mg/m2 4 times daily or as otherwise determined by BP response.199

Adults

Bronchospasm
Oral

Ephedrine tannate: 10–20 mg every 12 hours as needed; administered in fixed combination with other drugs (e.g., as Rynatuss).177

Ephedrine hydrochloride or sulfate self-medication: 12.5–25 mg every 4 hours as needed; used in fixed combination with guaifenesin.176 198 200

Parenteral

Ephedrine sulfate: Usually, 12.5–25 mg; give smallest effective dose.178 Further dosage should be determined by patient response.178

Hypotension
IV

Ephedrine sulfate: 5–25 mg; repeat in 5–10 minutes if necessary.175 Further dosage should be determined by BP response.199

If used during labor, administer only sufficient dosage to maintain BP ≤130/80 mm Hg.199

IM or Sub-Q

Ephedrine sulfate: 25–50 mg (range: 10–50 mg).175 178 Further dosage should be determined by BP response.199

If used during labor, administer only sufficient dosage to maintain BP ≤130/80 mm Hg.199

Cardiac Arrhythmias and Heart Block
Adams-Stokes Syndrome
IV

Ephedrine sulfate: 5–25 mg; repeat in 5–10 minutes if necessary.175

IM or Sub-Q

Ephedrine sulfate: 25–50 mg (range: 10–50 mg).175

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.176 198 200

Adults

Bronchospasm
Oral

Ephedrine hydrochloride or sulfate self-medication: Maximum 150 mg in any 24-hour period.176 198 200

Cautions for Ephedrine Hydrochloride

Contraindications

  • Concurrent or recent (i.e., within 2 weeks) therapy with an MAO inhibitor.176 177 198

  • Angle-closure glaucoma.178

  • General anesthesia with cyclopropane or halothane.178 (See Specific Drugs under Interactions.)

  • Generally should not be used if vasopressor drugs are contraindicated (e.g., in patients with thyrotoxicosis or diabetes mellitus, in obstetrics when maternal BP is >130/80 mm Hg, in patients with hypertension or other cardiovascular disorders).199

  • Known hypersensitivity to ephedrine or sympathomimetic drugs.175 178

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 (See Risks Associated with Dietary Supplements under Cautions.)

Risk of anginal pain in patients with coronary insufficiency or ischemic heart disease.178 Risk of potentially fatal arrhythmias in patients with organic heart disease or in those receiving drugs that sensitize the myocardium (e.g., cyclopropane, halothane).178

Caution in patients with cardiovascular disease (e.g., coronary insufficiency, angina pectoris, cardiac arrhythmias, unstable vasomotor system) and in those receiving digitalis.175 178

Concomitant Diseases

Use with caution in patients with CHD, hypertension, hyperthyroidism, diabetes mellitus, or prostatic hypertrophy.175 177 178 Patients with these 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.176 198 200

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

Sensitivity Reactions

Some commercially available preparations may contain the dye tartrazine (FD&C yellow No. 5); possible allergic reactions in susceptible individuals (e.g., those sensitive to aspirin).177

General Precautions

When used in fixed combination with other drugs, observe the usual cautions, precautions, and contraindications associated with all drugs in the preparation.176 177 198 200

CNS Effects

Nervousness, tremor, or insomnia may occur.176 Discontinue self-medication and consult a clinician if these symptoms persist or worsen.176

GI Effects

Nausea or loss of appetite may occur.176 Discontinue self-medication and consult a clinician if these symptoms persist or worsen.176

Prolonged Use

Prolonged parenteral use may produce a syndrome resembling an anxiety state.175 Tolerance may develop; effectiveness may return after the drug is withheld temporarily.175 178

Duration of Therapy

Self-medication in asthma: Discontinue and consult a clinician if symptoms are not improved within 1 hour or worsen.176 198 Discontinue if cough persists for >7 days, recurs, or is accompanied by fever, rash, or persistent headache.176

Misuse and Abuse

Potential for misuse and abuse.a

Specific Populations

Pregnancy

Category C.175 178

Parenteral ephedrine should not be used in obstetric patients when maternal BP is >130/80 mm Hg.178

Lactation

Distributed into milk.175 Use not recommended.175

Pediatric Use

Parenteral preparations: Safety and efficacy not established.178 Limited use in pediatric patients; dosage and limitations of use not established.178

Should not be used for self-medication in children <12 years of age unless otherwise directed by a clinician.177 198 200

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; safety and efficacy in older children currently under evaluation. 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 recently agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age. During the transition period, some preparations on pharmacy shelves will have the new recommendation (“do not use in children <4 years of age”), while others will have the previous recommendation (“do not use in children <2 years of age”). 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. Clinicians should ask caregivers about use of OTC cough/cold preparations to avoid overdosage.

Common Adverse Effects

Parenteral ephedrine: Nervousness, insomnia, restlessness, anxiety, tension, tremor, weakness, dizziness, vertigo, headache, confusion, delirium, hallucination, pallor, respiratory difficulty, hypertension (resulting in cerebral hemorrhage), tachycardia, palpitation, sweating, nausea, vomiting, anorexia, vesical sphincter spasm (resulting in difficult and painful urination), urinary retention (particularly in males with prostatism), precordial pain, cardiac arrhythmias.175 199

Interactions for Ephedrine Hydrochloride

Specific Drugs

Drug

Interaction

Comment

α-Adrenergic blocking agents

Vasopressor response to ephedrine decreased178

β-Adrenergic blocking agents

Antagonism of cardiac and bronchodilating effects of ephedrine178

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

Increased cardiosensitivity to ephedrine175 178

Contraindicated178

Atropine

Blocks the reflex bradycardia caused by ephedrine and enhances the pressor response to ephedrinea

Cardiac glycosides

Increased cardiosensitivity to ephedrine175 178

Use with caution175 178

Diuretics

Decreased arterial responsiveness to pressor drugs178

Guanethidine

Antagonism of the neuron blockade produced by guanethidine, resulting in loss of antihypertensive effectiveness or sudden rise in BP175 178

Increase guanethidine dosage if necessary178

Methyldopa

Pressor response to ephedrine decreased178

MAO inhibitors

Pressor effects of ephedrine increased; may result in hypertensive crisis or subarachnoid hemorrhage rarely175

Avoid use with or for 2 weeks after discontinuance of MAO inhibitors175 176

Oxytocics

Severe hypotension possible175

Reserpine

Pressor response to ephedrine decreased178

Sympathomimetic drugs

Additive effects and increased toxicity178

Avoid concomitant use178

Ephedrine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed following oral, IV, IM, or sub-Q administration.178 Peak serum concentrations attained within 2.6–3 hours following oral administration.120

Onset

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

IV administration: Pharmacologic effects occur almost immediately.178

IM administration: Pharmacologic effects occur within 10–20 minutes.178

Duration

Oral administration: Bronchodilation persists for 2–4 hours; pressor and cardiac responses persist for up to 4 hours.a

Parenteral administration: Pressor and cardiac responses persist for 1 hour.a

Distribution

Extent

Distributed into milk.175

Elimination

Metabolism

Slowly metabolized in the liver.178

Elimination Route

Ephedrine and its metabolites are excreted in urine; most of the drug is excreted as unchanged ephedrine.178 The rate of urinary excretion of ephedrine and its metabolites is dependent upon urinary pH.178

Half-life

About 3 hours when the urine is acidified to pH 5; about 6 hours when urinary pH is about 6.3.178

Stability

Storage

Parenteral

Injection

15–30°C.178 Protect from light.175 178

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextran 6% in dextrose 5%

Dextran 6% in sodium chloride 0.9%

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose–saline combinations

Dextrose 2½, 5, or 10% in water

Fructose 10% in sodium chloride 0.9%

Fructose 10% in water

Invert sugar 5 and 10% in sodium chloride 0.9%

Invert sugar 5 and 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

Metaraminol bitartrate

Nafcillin sodium

Penicillin G potassium

Incompatible

Hydrocortisone sodium succinate

Pentobarbital sodium

Phenobarbital sodium

Variable

Thiopental sodium

Y-site CompatibilityHID

Compatible

Bivalirudin

Dexmedetomidine HCl

Etomidate

Fenoldopam mesylate

Hetastarch in lactated electrolyte injection (Hextend)

Propofol

Incompatible

Thiopental sodium

Actions

  • Sympathomimetic agent; occurs naturally in plants of the genus Ephedra.172 179

  • Stimulates both α- and β-adrenergic receptors.172 175 178

  • Relaxes bronchial smooth muscle, stimulates cardiac muscle (producing positive inotropic effects),a constricts arterioles, increases BP, and stimulates the cerebral cortex and subcortical centers.175 178 198

  • Relaxes GI smooth muscle.175 Contracts urinary bladder trigone and sphincter and relaxes the detrusor muscle; may cause urinary retention.175

Advice to Patients

  • For self-medication in asthma, importance of not exceeding recommended dosages or frequency of administration unless otherwise instructed by a clinician.176 198 200

  • For self-medication in asthma, importance of discontinuing therapy and contacting a clinician if symptoms are not improved within 1 hour or they become worse.176 198

  • For self-medication in asthma, importance of discontinuing therapy and contacting a clinician if cough persists for >7 days, recurs, or is accompanied by fever, rash, or persistent headache.176 198 200

  • For self-medication in asthma, importance of contacting a clinician if nervousness, tremor, sleeplessness, nausea, or loss of appetite persists or becomes worse.176 198 200

  • For asthma, advise that ephedrine should be used for self-medication only if asthma was previously diagnosed by a clinician.176 198 200 Before considering self-medication, inform clinician of any history of hospitalization for asthma.176 198 200

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).175 176 178 Importance of avoiding MAO inhibitors and allowing 2 weeks to elapse after discontinuing these antidepressants.175 176 178 198 199 200

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.175 176 178

  • Importance of informing patients of other important precautionary information.175 176 178 (See Cautions.)

Preparations

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

In February 2004, FDA issued a final regulation declaring that dietary supplements containing ephedrine alkaloids are adulterated under the Federal Food, Drug, and Cosmetic Act.189 In August 2006, FDA’s position was upheld by the US Court of Appeals for the 10th Circuit in Denver; sale of these dietary supplements in the US is illegal and subject to FDA enforcement action.207 (See Risks Associated with Dietary Supplements under Cautions.)

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

Ephedrine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

crystals or granules (hydrous or anhydrous)*

* 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

Bulk

Crystals*

Bulk

Powder*

Parenteral

Injection

50 mg/mL*

Ephedrine Sulfate Injection

Abbott, Bedford

Ephedrine and its salts are also commercially available in combination with antitussives, expectorants, sedatives, and/or antihistamines.

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

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