Ephedrine Hydrochloride

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

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 (cyclopropane or halogenated hydrocarbon)	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 Compatibility^HID

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

ActionsActions

• 
  

  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 10^th 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.

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions March 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.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Edmonds ME, Archer AG, Watkins PJ. Ephedrine: a new treatment for diabetic neuropathic oedema. Lancet. 1983; 1:548-51. [IDIS 167932] [PubMed 6131255]

101. Food and Drug Administration. Over-the-counter drug products; final monographs for antiemetic, antitussive, bronchodilator, and antihelmintic drug products; updating and technical changes. Fed Regist. 1988; 53:35808-10.

102. Drug Enforcement Administration. Elimination of threshold for ephedrine. Final Rule. [21 CFR Parts 1310 and 1313] Fed Regist 1994; 59:51365-7.

103. Drug Enforcement Administration. Implementation of the Domestic Chemical Diversion Control Act of 1993 (pub. L. 103-200). [21 CFR parts 1307, 1309, 1310, 1313 and 1316] Fed Regist. 1994; 59:51887-908.

104. Drug Enforcement Administration, Washington, DC: Personal communication; 1994 Dec.

105. US Department of Justice, Washington, DC: Personal communication; 1994 Nov.

106. Anon. U-turn: states put ephedrine OTCs back behind counter. Drug Topics. 24 Oct 1994; 138:27.

107. Anon. Panels urge removal of OTC ephedrine. Generic Line. 1994; 11:5.

108. Drug Enforcement Administration. Elimination of threshold for ephedrine. Proposed Rule. [21 CFR Part 1310] Fed Regist. 1994; 59:12562-3.

109. Anon. Federal and state actions against ephedrine abuse. NC Board of Pharm. 1994; 16:2.

110. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; proposed amendment of monograph for OTC bronchodilator drug products. Notice of proposed rulemaking. [21 CFR Parts 310 and 341] Fed Regist 1995; 60:38643-7.

111. Public Law 104-237, 104th Cong., (3 October 1996), Comprehensive Methamphetamine Control Act of 1996.

112. Maltz GA. Methamphetamine law will control bulk sales of “precursor chemicals”: earlier DEA ruling nullified. Pharmacy Today. 1996; 2:1,17.

113. Food and Drug Administration. Dietary supplements containing ephedrine alkaloids. Proposed rule. [21 CFR Part 111] Fed Regist. 1997; 62:30678-724.

114. Anon. FDA proposes constraints on ephedrine dietary supplements. Am J Health-Sys Pharm. 1997; 54:1578.

115. Anon. FDA proposes safety measures for ephedrine dietary supplements. HHS News. 1997 (June 2); P97-15.

116. Segal M. FDA warns against drug promotion of “Herbal Fen-Phen”. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1997 Nov 6.

117. Whitmore A. FDA statement on street drugs containing botanical ephedrine. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1996 Apr 10.

118. Anon. Adverse events associated with ephedrine-containing products—Texas, December 1993 September 1995. MMWR Morb Mortal Wkly Rep. 1996; 45:689-93. [PubMed 8772203]

119. Drug Enforcement Administration. Implementation of the Comprehensive Methamphetamine Control Act of 1996; regulation of pseudoephedrine, phenylpropanolamine, and combination ephedrine drug products and reports of certain transactions to nonregulated persons. 21 CFR Parts 1300, 1309, 1310. Proposed rule. [DEA No. 163P] Fed Regist. 1997; 62:52294-304.

120. Gurley BJ, Gardner SF, White LM et al. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit. 1998; 20:439-45. [IDIS 411627] [PubMed 9712471]

121. Schuller DE. Adverse effects of brompheniramine on pulmonary function in a subset of asthmatic children. J Allergy Clin Immunol. 1983; 72:175-9. [IDIS 174299] [PubMed 6886255]

122. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; final monograph for OTC antihistamine drug products. 21 CFR Parts 201, 310, 341, and 369. Final rule. [Docet No. 76N-052H] Fed Regist. 1992; 57:58356-76.

123. Meltzer EO. To use or not to use antihistamines in patients with asthma. Ann Allergy. 1990; 64(Part II):183-6. [IDIS 297019] [PubMed 1967918]

124. Lantner R, Tobin MC. Pharmacist advice to asthmatics regarding antihistamine use. Ann Allergy. 1991; 66:411-3. [IDIS 282619] [PubMed 2035904]

125. Pierson WE, Virant FS. Antihistamines in asthma. Ann Allergy. 1989; 63(Part II):601-2. [IDIS 301484] [PubMed 2574551]

126. Food and Drug Administration. Sleep aids and antiemetics. From: FDA Bulletin Board. 1993 Aug 26.

127. Simons FER, Simons KJ. The pharmacology and use of H1-receptor-antagonist drugs. N Engl J Med. 1994; 330:1663-70. [IDIS 330632] [PubMed 7909915]

128. Weintraub M. Histamine H1 antagonists. N Engl J Med. 1994; 331:1019. [IDIS 337173] [PubMed 7916125]

129. Cerulli J, Lomaestro BM, Malone M. Update on the pharmacotherapy of obesity. Ann Pharmacother. 1998; 32:88-102. [IDIS 399703] [PubMed 9475827]

130. Astrup A, Toubro S, Christensen NJ et al. Pharmacology of thermogenic drugs. Am J Clin Nutr. 1992; 55:246S-8S. [IDIS 290478] [PubMed 1345887]

131. Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing supplements. Am J Health-Syst Pharm. 2000; 57:963-9. [IDIS 446390] [PubMed 10832496]

132. Hasegawa GR. Uncertain quality of dietary supplements: History repeated. Am J Health-Syst Pharm. 2000; 57:951. [IDIS 446388] [PubMed 10832494]

133. Zeisel SH. Regulation of “Nutraceuticals”. Science. 1999; 285:1853-5. [PubMed 10515789]

134. Gugliotta G. Ephedra lawsuits show big increase. Washington Post. 2000; Jul 23:A01.

135. Hahm H, Kujawa J, Ausburger L. Comparison of melatonin products against USP’s nutritional supplements standards and other criteria. J Am Pharm Assoc. 1999; 39:27-31.

136. Slifman NR, Obermeyer WR, Aloi BK et al. Contamination of botanical dietary supplements by Digitalis lanata. N Engl J Med. 1998; 339:806-11. [IDIS 411166] [PubMed 9738088]

137. Parasrampuria J, Schwartz K. Quality control of dihydroepiandrosterone dietary supplement products. JAMA. 1998; 280:27-31.

138. Liberti LE, Der Marderosian A. Evaluation of commercial ginseng products. J Pharm Sci. 1978; 67:1487-9. [PubMed 702314]

139. Cui J, Garle M, Eneroth P et al. What do commercial ginseng preparations contain? Lancet. 1994; 344:134. Letter.

140. Heptinstall S, Awang DVC, Dawson BA et al. Parthenolide content and bioactivity of feverfew (Tanacetum parthenium (L.) Schultz-Bip). Estimation of commercial and authenticated feverfew products. J Pharm Pharmacol. 1992; 44:391-5. [PubMed 1359053]

141. Webb G. “fX”: Chemically adulterated product does not contain kava. Herbalgram. 1997; 39:9.

142. August K, Brooks L (California Department of Health and Human Services). State health director warns consumers about prescription drugs in herbal products. Rockville, MD; 2000 Feb 15. News release No. 09-00. News release from FDA web site.

143. Ko RJ. Adulterants in Asian patent medicines. N Engl J Med. 1998; 339:806-11. [IDIS 411166] [PubMed 9738088]

144. KlepserTB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health-Syst Pharm. 1999; 56:125-38. [PubMed 10030529]

145. Food and Drug Administration. Dietary supplements containing ephedrine alkaloids; withdrawal in part. Fed Regist. 2000(Apr 3); 65(64):17474-7.

146. Smith IK. Ginseng surprise. An independent report finds that what’s listed on a supplement’s label is not always what’s inside. Time. 2000(Jul 31):156.

147. Anon. Product review: Asian & American ginseng. ConsumerLabs.com. White Plains, NY; 2000 Aug 11. From ConsumerLab.com web site.

148. Anon. Product review: Gingko biloba. ConsumerLabs.com. White Plains, NY; 2000 Aug 11. From ConsumerLab.com web site. 8/11/00.

149. Anon. Product review: Saw palmetto. ConsumerLabs.com. White Plains, NY; 2000 Aug 11. From ConsumerLab.com web site. 2000 Aug 11.

150. Anon. Product review: SAMe. ConsumerLabs.com. White Plains, NY; 2000 Aug 11. From ConsumerLab.com web site.

151. Anon. Product review: Glucosamine and chondroitin. ConsumerLabs.com. White Plains, NY; 2000 Aug 11. From ConsumerLab.com web site.

152. Anon. About ConsumerLab.com. ConsumerLabs.com. White Plains, NY; 2000 Aug 11. From Consumerlab.com web site.

153. US Food and Drug Administration. Current good manufacturing practice in manufacturing, packing, or holding dietary supplements: proposed rule. Fed Regist. 1997; 62:5699-709.

154. US Food and Drug Administration. Dietary supplements containing ephedrine alkaloids: availability. Fed Regist. 2000; 65:17510-2.

155. US Food and Drug Administration. “Dear colleague” letter about August 8, 2000 public meeting concerning the safety of dietary supplements containing ephedrine alkaloids. Rockville, MD; FDA Center for Food Safety and Nutrition. 2000 Aug 7. From FDA web site.

156. Levitt JA, US Food and Drug Administration. Dietary supplement strategy (ten year plan). Rockville, MD; FDA Center for Food Safety and Nutrition. 2000 Aug 7. From FDA web site.

157. Ephedra Education Council. Scientific and medical experts support current national standards for ephedra. 2000 Aug 7. From PR Newswire web site.

158. US Food and Drug Administration Center for Drug Evaluation and Research. Guidance for industry: botanical drug products. Draft guidance. 2000 Aug 16. From FDA web site.

159. US Food and Drug Administration. Dietary supplements containing ephedrine alkaloids: administrative docket update; availability. Fed Regist. 2000; 65:17509-10.

160. US Food and Drug Administration. Dietary supplement health and education act of 1994. Rockville, MD; FDA Center for Food Safety and Applied Nutrition. 2000 Oct 15. From FDA web site.

161. Reviewers’ comments (personal observations).

162. Powell T, Hsu FF, Turk J et al. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis. 1998; 32:153-9. [IDIS 409911] [PubMed 9669437]

163. Lau KK, Lai CK, Chan AYW. Phenytoin poisoning after using Chinese proprietary medicines. Hum Exp Toxicol. 2000; 19:385-6. [PubMed 11002387]

164. Huang WF, Wen KC, Hsiao ML. Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol. 1997; 37:344-50. [IDIS 385760] [PubMed 9115061]

165. Gilbert-Barness E, Drut RM. Association of sympathomimetic drugs with malformations. Vet Hum Toxicol. 2000 Jun;42:168-71.

166. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med. 2000; 343:1833-8. [IDIS 457118] [PubMed 11117974]

167. Ben-David B, Miller G, Gavriel R et al. Low-dose bupivacaine-fentanyl spinal anesthesia for cesarean delivery. Reg Anesth Pain Med. 2000; 25:235-9. [PubMed 10834776]

168. National Nutritional Foods Association. NNFA GMP Certification Program: an overview. 2000 Nov 9. From NNFA web site.)

169. US Food and Drug Administration. Dietary supplements containing ephedrine alkaloids; availability; reopening of comment period. [Docket No. 00N-1200] Fed Regist. 2000; 65:46721-2.

170. US Food and Drug Administration. Dietary supplements containing ephedrine alkaloids; availability; extension of comment period. [Docket No. 00N-1200] Fed Regis