Naloxone Hydrochloride

Pronunciation

Class: Opiate Antagonists
VA Class: CN102
CAS Number: 357-08-4
Brands: Narcan, Talwin Nx, Suboxone

Warning(s)

REMS:

FDA approved a REMS for naloxone to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of naloxone and consists of the following: medication guide, elements to assure safe use, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Essentially a pure opiate antagonist.113

Uses for Naloxone Hydrochloride

Opiate-induced Depression and Acute Opiate Overdosage

Treatment of opiate-induced depression, including respiratory depression, caused by natural and synthetic opiates such as anileridine, codeine, diphenoxylate, fentanyl, heroin, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, concentrated opium alkaloids hydrochlorides, and propoxyphene.113 116

Useful for the treatment of opiate-induced depression, including respiratory depression, caused by certain opiate partial agonists including butorphanol, nalbuphine, pentazocine, and cyclazocine.113

Useful for the treatment of mild or moderate as well as severe opiate-induced respiratory depression.b

Administration should be accompanied by other resuscitative measures such as administration of oxygen, mechanical ventilation, or artificial respiration.b

Duration of respiratory depression following opiate agonist overdosage may be longer than the duration of naloxone action and other more immediate supportive and symptomatic treatment also should be initiated.d

Use in patients physically dependent on opiate agonists may precipitate an acute withdrawal syndrome that cannot be readily suppressed while the action of the antagonist (naloxone) persists.d

Slideshow: Prescription Drug Addiction - Top 18 Facts for You and Your Family

If opiate abstinence syndrome is precipitated by naloxone, symptoms will be apparent within a few minutes and maximal within 30 minutes after administration; effects usually will be more severe than those following withdrawal of the opiate agonist.d

Some value in the management of buprenorphine overdosage but should not be relied on for treatment of respiratory depression.c Reversal of agonist effects develops slowly.113

Not effective in the management of acute toxicity caused by levopropoxyphene.b

Diagnosis of Opiate Overdosage

Aid in the diagnosis of suspected acute opiate overdosage (e.g., in the absence of confirmatory history and/or definitive diagnostic clinical findings).113 e

Diagnosis of Chronic Opiate Abuse (Naloxone Challenge Test)

Has been used as an aid in the diagnosis of chronic opiate abuse, but preferable to use chemical methods to detect the presence of opiates in urine, since naloxone may precipitate severe withdrawal symptoms in patients physically dependent on opiates.b

Screening test (the naloxone challenge test) prior to induction of naltrexone therapy for opiate cessation in patients formerly dependent on opiates who have completed detoxification.b Such screening can avoid precipitating opiate withdrawal following administration of naltrexone.d

Alcohol- or Clonidine-induced Coma

Has been used in intoxicated patients to reverse alcohol-induced coma and to reverse clonidine-induced coma and respiratory depression.b

Detoxification and Maintenance Treatment of Opiate Dependence

A combination of methadone hydrochloride and naloxone hydrochloride in a ratio of 20:1 has been administered orally in the detoxification or maintenance treatment of opiate dependence in conjunction with appropriate social and medical services.b

May prevent opiate euphoria and thus decrease the desire for opiates.b

Has been used for rapid or ultrarapid detoxification in the management of opiate withdrawal in opiate-dependent individuals, both in inpatient and outpatient settings.112

Rapid opiate detoxification involves the administration of opiate antagonists such as naloxone and/or naltrexone to shorten the time period of detoxification.112

Ultrarapid detoxification is similar, but involves the administration of opiate antagonists (i.e., naloxone, naltrexone) while the patient is sedated or under general anesthesia.112

Risk of adverse respiratory and cardiovascular effects associated with this procedure must be considered as well as the costs of general anesthesia and hospitalization.112

Minimization of Pentazocine or Buprenorphine Abuse Potential

Used orally in fixed combination with pentazocine hydrochloride or buprenorphine hydrochloride to minimize abuse potential of pentazocine or buprenorphine; antagonistic effect of naloxone will predominate if the combinations are administered parenterally and/or if usual oral doses are exceeded.114 115

Naloxone Hydrochloride Dosage and Administration

Administration

Administer by IV, sub-Q, or IM injection, or by IV infusion.113 116

IV administration is recommended for emergency situations.113 116

Because absorption may be erratic or delayed, AAP does not endorse sub-Q or IM injection in children or neonates with opiate intoxication.113

When IV access cannot be established in emergency situations, consider administration via an endotracheal tube in adult and pediatric patients (this route not recommended in neonates).100 101 102 104 105 106 107 108 109 110 111 116 Also consider intraosseous injection in pediatric patients.116

IV Administration

For drug compatibility information, see Compatibility under Stability.

Continuous IV infusions may be most appropriate in patients who require higher doses, continue to experience recurrent respiratory or CNS depression after effective therapy with repeated doses, and/or in whom the effects of long-acting opiates are being antagonized.b

Dilution

Continuous IV infusion: 2 mg of naloxone hydrochloride may be diluted in 500 mL of 0.9% sodium chloride or 5% dextrose injection to produce a solution containing 0.004 mg/mL (4 mcg/mL).113

Rate of Administration

Titrate in accordance with patient’s response.113

Dosage

Available as naloxone hydrochloride; dosage expressed in terms of the salt.113

Pediatric Patients

Postoperative Opiate Depression
IV

Initial dosage: Usually, 0.005–0.01 mg, given at 2- to 3-minute intervals until desired response (i.e., adequate ventilation and alertness without substantial pain or discomfort) is obtained.113

Additional doses may be necessary at 1- to 2-hour intervals depending on response and dosage and duration of action of the opiate administered.113 (See Excessive Dosage in Surgery under Cautions.)

Opiate Overdosage
Diagnosis
IV

Children: Initially, 0.01 mg/kg; if this dose does not produce the expected response, may give a subsequent 0.1-mg/kg dose.113

Treatment

Duration of opiate action often exceeds that of naloxone; opiate depressant effects may return as the effects of naloxone diminish, and additional naloxone doses (or a continuous IV infusion) may be required.113 116

Closely observe the patient for a day or longer regardless of degree of apparent improvement.b

IV

Children: Initially, 0.01 mg/kg; if this dose does not produce the desired degree of response, may give a subsequent 0.1-mg/kg dose.113 f

Alternatively, children <5 years of age or weight ≤20 kg: 0.1 mg/kg; repeat as necessary.116 b

Alternatively, children ≥5 years of age or weight >20 kg: 2 mg; repeat as necessary.116 b

Continuous IV infusion dosage regimens have not been well established, and the rate of administration must be titrated according to the patient’s response.b

Experience with continuous IV infusions in children is limited, but children may require higher infusion rates on a mg/kg basis than adults.b

Infusion rates in children usually have ranged from 0.024–0.16 mg/kg per hour; alternatively, a pediatric infusion rate of 0.4 mg/hour has been suggested.b

Intraosseous or Endotracheal

Use lower doses to reverse respiratory depression from therapeutic opiate use.116

Adults

Postoperative Opiate Depression
IV

Initial dosage: Usually, 0.1–0.2 mg, given at 2- to 3-minute intervals until desired response (i.e., adequate ventilation and alertness without substantial pain or discomfort) is obtained; additional doses may be necessary at 1- to 2-hour intervals depending on response and dosage and duration of action of the opiate administered.113

Alternatively, 0.005 mg/kg, repeated after 15 minutes if necessary.b

Continuous IV infusion: 0.0037 mg/kg per hour.b

Opiate Overdosage
Diagnosis
IV

Initial dosage: Usually, 0.4–2 mg IV, administered at 2- to 3-minute intervals if necessary; if no response is observed after a total of 10 mg of the drug has been administered, the depressive condition may be caused by a drug or disease process not responsive to naloxone.113

Treatment

Duration of opiate action often exceeds that of naloxone; opiate depressant effects may return as the effects of naloxone diminish, and additional naloxone doses (or a continuous IV infusion) may be required.113 116

Closely observe the patient for a day or longer regardless of the degree of apparent improvement.b

IV

Initial dosage: Usually, 0.4–2 mg IV, administered at 2- to 3-minute intervals if necessary; if no response is observed after a total of 10 mg of the drug has been administered, the depressive condition may be caused by a drug or disease process not responsive to naloxone.113 116

Continuous IV infusion dosage regimens of naloxone have not been well established, and the rate of administration must be titrated according to the patient’s response.b

IV infusion: IV loading dose of 0.4 mg, followed by a continuous IV infusion at an initial rate of 0.4 mg/hour; alternatively, other clinicians have recommended that an IV loading dose of 0.005 mg/kg be given, followed by continuous infusion of 0.0025 mg/kg per hour.b

IV infusion: Alternatively, IV loading dose of 0.005 mg/kg, followed by continuous IV infusion of 0.0025 mg/kg per hour.b

For patients with chronic opiate addiction, use lower dose and titrate slowly to minimize adverse cardiovascular effects and withdrawal symptoms.116

IM or Sub-Q

0.4–0.8 mg; repeated as necessary.116

Diagnosis of Chronic Opiate Abuse (Naloxone Challenge Test)

Performed prior to induction of naltrexone therapy in patients formerly physically dependent on opiates who have completed detoxification and in those suspected of having been dependent on opiates.

Do not perform the naloxone challenge test in patients who are exhibiting manifestations of opiate withdrawal, those whose urine shows evidence of opiates, or those in whom there is a high degree of suspicion that opiates are still being used, since naloxone may precipitate potentially severe opiate withdrawal.

If manifestations of opiate withdrawal are evident following naloxone challenge test, naltrexone therapy should not be attempted.

During the appropriate period in the naloxone challenge test, the patient should be closely monitored for the appearance of manifestations of opiate withdrawal and vital signs should be monitored.

If manifestations of opiate withdrawal are evident following the naloxone challenge test, do not initiate naltrexone therapy due to potential risk of precipitating more severe and prolonged withdrawal with naltrexone; naloxone challenge test may be repeated in 24 hours in these patients.

If evidence of withdrawal is absent, naltrexone therapy may be initiated.

Some clinicians caution that even minor and/or transient GI symptoms following naloxone challenge be considered evidence of withdrawal since patients with such symptoms will often develop severe and disturbing GI symptoms if naltrexone therapy is then initiated.

IV

Use a sterile syringe containing 0.8 mg of naloxone hydrochloride.

Initially, a 0.2-mg IV dose and, while the needle remains in the vein, observe the patient for 30 seconds for evidence of opiate withdrawal.

Alternatively, an initial 0.2-mg IV dose, then observe patient for 15 minutes for evidence of withdrawal.

Manifestations of withdrawal include, but are not limited to, nasal stuffiness, rhinorrhea, lacrimation, yawning, sweating, tremor, abdominal cramps, vomiting, piloerection, myalgia, and skin crawling.

If no evidence of withdrawal, inject the remaining 0.6-mg IV dose and observe the patient for an additional 20 minutes for evidence of withdrawal.

Some clinicians recommend that a total IV dose of 2 mg be used in the test since withdrawal has been precipitated by the first oral dose of naltrexone despite a negative naloxone challenge test using lower doses and a false-negative test rarely occurs with the 2-mg naloxone hydrochloride dose.

Sub-Q

Inject the entire 0.8-mg dose and observe the patient for 20 minutes for evidence of opiate withdrawal.

If evidence of opiate withdrawal is present, naltrexone therapy should be delayed and the naloxone challenge test repeated in 24 hours with the 0.8-mg dose and every 24 hours until results are negative.

If it is uncertain whether the patient is opiate free or is undergoing opiate withdrawal following an initial test, the naloxone challenge test should be repeated at that time with a 1.6-mg dose.

To repeat the naloxone challenge test in these patients, a 1.6-mg dose of naloxone hydrochloride should be injected IV and the patient observed for evidence of opiate withdrawal; if evidence of opiate withdrawal is absent, naltrexone therapy may be initiated.

Diagnosis of Opiate Dependence
IM, then IV

Initial single dose of 0.16 mg IM; if no withdrawal manifestations are evident after 20–30 minutes, a second dose of 0.24 mg is given IV.b

Negative test results assumed if no withdrawal manifestations are apparent within 30 minutes after the second dose.b

Withdrawal manifestations induced by naloxone begin to diminish 20–40 minutes after injection and are essentially gone within 1.5 hours.b

Prescribing Limits

Adults

Known or Suspected Opiate Overdosage
IV, IM or Sub-Q

If no response is observed after a total of 10 mg is been administered, the depressive condition may be caused by a drug or disease process not responsive to naloxone.113

Special Populations

Hepatic Impairment

No specific dosage recommendations.b

Renal Impairment

No specific dosage recommendations.b

Geriatric Patients

No specific dosage recommendations; in general, dose selection should be cautious, usually initiating at the lower end or the normal range.113

Cautions for Naloxone Hydrochloride

Contraindications

  • Known hypersensitivity to naloxone or any ingredient in the formulation.113

Warnings/Precautions

Warnings

Additional Resuscitative Measures

When used in the management of acute opiate overdosage, other resuscitative measures (e.g., maintenance of an adequate airway, artificial respiration, cardiac massage, vasopressor agents) should be readily available and used when necessary.113

Excessive Dosage in Surgery

Avoid excessive dosage following the use of opiates during surgery because naloxone may result in excitement, agitation, an increase in BP, and clinically important reversal of analgesia; a reversal of opiate effects achieved too rapidly may induce nausea, vomiting, sweating, tremor, tachycardia, increased BP, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest, which may result in death.113

Physical Opiate Dependence

Caution in patients known or suspected to be physically dependent on opiates (including neonates born to women who are opiate dependent) because severe withdrawal manifestations may be precipitated.113

General Precautions

Cardiovascular Disease

Caution in patients with preexisting cardiovascular disease or in those receiving potentially cardiotoxic drugs, since serious adverse cardiovascular effects (e.g., ventricular tachycardia and fibrillation, pulmonary edema, cardiac arrest) resulting in death, coma, and encephalopathy have occurred in postoperative patients following administration of naloxone.113 (See Common Adverse Effects under Cautions.)

Repeat Administration

Carefully monitor patients who have responded to naloxone since the duration of action of some opiates may exceed that of naloxone; monitor pediatric patients for at least 24 hours.113 Give repeated doses of naloxone to these patients when necessary.113

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C;113 considered category B by some experts.g

Lactation

Not known whether naloxone is distributed into milk.113 g Caution advised if used in nursing women.113

Pediatric Use

Safety and efficacy in management of hypotension associated with septic shock not established in pediatric patients.113 In a study of 2 neonates with septic shock, treatment with naloxone produced positive pressor response; however, one patient subsequently died after intractable seizures.113

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.113 Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.113

Hepatic Impairment

Safety and efficacy not established; use with caution.113

Renal Impairment

Safety and efficacy not established; use with caution.113

Common Adverse Effects

Nausea and vomiting rarely postoperatively with parenteral dose exceeding that usually recommended; a causal relationship has not been established.b

Analgesia reversal, excitement, agitation, and increased BP may occur with excessive postoperative doses.113

Postoperative use: Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest; sequelae include death, coma, and encephalopathy.113

Opiate overdosage: Tremor and hyperventilation associated with an abrupt return to consciousness.b

Opiate dependence: Abrupt dependence reversal may precipitate acute withdrawal.113

Adverse cardiovascular effects have occurred most frequently in postoperative patients with preexisting cardiovascular disease or in those receiving other drugs that produce similar adverse cardiovascular effects. (See Cardiovascular Disease under Cautions.)

Interactions for Naloxone Hydrochloride

Specific Drugs

Drug

Interaction

Comments

Cardiotoxic drugs

Serious adverse cardiovascular effects (e.g., ventricular tachycardia and fibrillation, pulmonary edema, cardiac arrest) resulting in death, coma, and encephalopathy reported in postoperative patients113

Use concomitantly with caution113

Methohexital

Methohexital appears to block the acute onset of withdrawal symptoms induced by naloxone in opiate addicts113

Naloxone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly inactivated following oral administration.b

Although effective orally, doses much larger than those required for parenteral administration are required for complete antagonism.b

Onset

IV: Within 1–2 minutes.b

Sub-Q or IM: Within 2–5 minutes.b

Duration

Depends on the dose and route of administration and is more prolonged following IM than IV administration.113

Distribution

Extent

Parenteral: Rapidly distributed into body tissues and fluids.113

Readily (within 2 minutes) crosses the placenta.113 g

Unknown whether distributed into milk.113 g

Plasma Protein Binding

Weakly bound to plasma proteins (mainly albumin).113

Elimination

Metabolism

Rapidly metabolized in the liver, principally by conjugation with glucuronic acid.113

Major metabolite is naloxone-3-glucuronide.113

Also undergoes N-dealkylation and reduction of the 6-keto group followed by conjugation.b

Elimination Route

Oral or IV dose: 25–40% excreted as metabolites in urine in 6 hours, about 50% in 24 hours, and 60–70% in 72 hours.113

Half-life

Adults: 30–81 minutes.113

Neonates: About 3 hours.113

Stability

Storage

Parenteral

Injection

25°C (may be exposed to 15–30°C); protect from light.113

Stable at pH 2.5–5.b

Use diluted solutions (e.g., 4 mcg/mL in 5% dextrose or 0.9% sodium chloride injection) within 24 hours; discard unused portions after 24 hours.113

Compatibility

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

Parenteral

Do not mix with preparations containing bisulfite, metabisulfite, long-chain or high molecular weight anions, or any solution having an alkaline pH.113

Drug Compatibility
Admixture CompatibilityHID

Compatible

Verapamil HCl

Y-Site CompatibilityHID

Compatible

Fenoldopam mesylate

Linezolid

Propofol

Incompatible

Amphotericin B cholesteryl sulfate complex

Lansoprazole

Actions

  • Essentially a pure opiate antagonist.113

  • In usual doses in patients who have not recently received opiates, naloxone exerts little or no pharmacologic effect.113

  • In patients who have received large doses of morphine or other analgesic drugs with morphine-like effects, naloxone antagonizes most of the effects of the opiate.113

  • Increase in respiratory rate and minute volume, decrease toward normal in arterial PCO2, and return to normal in blood pressure if depressed.b

  • Because the duration of action of naloxone is generally shorter than that of the opiate, the effects of the opiate may return as the effects of naloxone dissipate.113

  • Antagonizes opiate-induced sedation or sleep.b

  • Does not produce tolerance or physical or psychological dependence.113

  • It is thought to act as a competitive antagonist at mc, κ, and σ opiate receptors in the CNS; it is thought that the drug has the highest affinity for the μ receptor.113

Advice to Patients

  • Inform family about use and administration of drug.PDH

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

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

Preparations

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

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

Naloxone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

0.4 mg/mL*

Naloxone Hydrochloride Injection

Narcan

Endo

1 mg/mL

Naloxone Hydrochloride Injection

Pentazocine and Naloxone Hydrochlorides

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

Pentazocine Hydrochloride 50 mg (of pentazocine) and Naloxone Hydrochloride 0.5 mg (of naloxone)

Pentazocine and Naloxone Hydrochlorides Tablets (C-IV)

Talwin Nx Caplets (C-IV; scored)

Sanofi-Aventis

Naloxone Hydrochloride Dihydrate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Sublingual

Tablets

0.5 mg (of naloxone) with Buprenorphine Hydrochloride 2 mg (of buprenorphine)

Suboxone (C-III)

Reckitt Benckiser

2 mg (of naloxone) with Buprenorphine Hydrochloride 8 mg (of buprenorphine)

Suboxone (C-III)

Reckitt Benckiser

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Pentazocine-Naloxone HCl 50-0.5MG Tablets (WATSON LABS): 30/$42.99 or 90/$112.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 27, 2011. 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. Brown DH, Kasuya A, Leiken JB. Endotracheal administration in the critical care setting. J Emerg Med. 1987; 5:407-14. [PubMed 3312392]

101. Ward JT Jr. Endotracheal drug therapy. Am J Emerg Med. 1983; 1:71-2. [PubMed 6393996]

102. Tandberg D. Endotracheal naloxone. Am J Emerg Med. 1983; 1:366-7. [PubMed 6680644]

103. Tandberg D, Abercrombie D. Treatment of heroin overdose with endotracheal naloxone. Ann Emerg Med. 1982; 11:443-5. [PubMed 7103164]

104. Greenberg MI. The use of endotracheal medication in cardiac emergencies. Resuscitation. 1984; 12:155-65. [PubMed 6096940]

105. Hahnel J, Lindner KH, Ahnefeld FW. Endobroncial administration of emergency drugs. Resuscitation. 1989; 17:261-72. [PubMed 2548271]

106. Greenberg MI, Roberts JR, Baskin SI. Endotracheal naloxone reversal of morphine-induced respiratory depression in rabbits. Ann Emerg Med. 1980; 9:289-92. [PubMed 7386953]

107. Raehl CL. Endotracheal drug therapy in cardiopulmonary resuscitation. Clin Pharm. 1986; 5:572-9. [IDIS 217499] [PubMed 3527527]

108. American Academy of Pediatrics Committee on Drugs. Emergency drug doses for infants and children. Pediatrics. 1988; 81:462-5. [PubMed 3422026]

109. American Academy of Pediatrics Committee on Drugs. Emergency drug doses for infants and children and naloxone use in newborns: clarification. Pediatrics. 1989; 83:803. [IDIS 254337] [PubMed 2717301]

110. American Academy of Pediatrics Committee on Drugs. Naloxone dosage and route of administration for infants and children: addendum to emergency drug doses for infants and children. Pediatrics. 1990; 86:484-5. [IDIS 273346] [PubMed 2388800]

111. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Guidelines for cardiopulmonary resuscitation and emergency cardiac care. JAMA. 1992; 268:2171-302. [PubMed 1404767]

112. O’Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA. 1998; 279:229-34.

113. Endo Pharmaceuticals. Narcan (naloxone hydrochloride injection, USP) prescribing information. Chadds Ford, PA; 2003 Jul.

114. Reckitt Benckiser Pharmaceuticals, Inc. Suboxone (buprenorphine hydrochloride and naloxone hydrochloride dihydrate) sublingual tablets and Subutex (buprenorphine hydrochloride) sublingual tablets prescribing information. Richmond, VA. Accessed 2005 Nov 7.

115. Sanofi-Synthelabo Inc. Talwin NX (pentazocine and naloxone hydrochlorides) prescribing information. New York, NY; 2003 May.

116. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

117. Eigel B. (American Heart Association, Dallas, TX): Personal communication; 2006 Dec 18.

118. field JM, Hazinski MF, Gilmore D, eds. Handbook of emergency cardiovascular care for healthcare providers. Dallas, TX: American Heart Associaiton; 2005:95.

b. AHFS drug information 2004. McEvoy GK, ed. Naloxone. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2093-5.

c. AHFS drug information 2004. McEvoy GK, ed. Buprenorphine. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2067-74.

d. AHFS drug information 2004. McEvoy GK, ed. Opiate agonists general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2030-35.

e. Goldfrank LR, Flomenbaum NE, Lewin NA, et al. Goldfrank’s toxicologic emergencies. 7th ed. New York: McGraw-Hill; 2002: 909.

f. Behrman RE, Kliegman RM, Jenson HB. Nelson textbook of pediatrics. 17th ed. Elsevier Publishing: 2470.

g. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2002: 969.

PDH. Schilling McCann JA, Publisher. Pharmacists drug handbook. 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins and American Society of Health-System Pharmacists; 2003.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1201-3.

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