Brand names: Kloxxado, Narcan, Zimhi
Drug class: Opoid Antagonists

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Opioid antagonist.^{113 120 127 404 405}

Uses for Naloxone Hydrochloride

Opioid-induced Depression and Acute Opioid Overdosage

Treatment of opioid-induced depression, including respiratory depression, caused by natural and synthetic opioids (e.g., codeine, diphenoxylate, fentanyl, heroin, hydromorphone, levorphanol, meperidine, methadone, morphine, oxymorphone, concentrated opium alkaloids, propoxyphene).^{113 120 127 404 405}

Useful for treatment of opioid-induced depression, including respiratory depression, caused by certain opioid partial agonists including butorphanol, nalbuphine, and pentazocine.^{113 120 127 404 405} However, reversal of respiratory depression from overdosage of opioid partial agonists may be incomplete and require higher or more frequent naloxone doses.^{113 120 127 404 405}

May be used in community (nonmedical) settings for emergency treatment of known or suspected opioid overdosage, as manifested by respiratory and/or CNS depression.^{124 125 126 139} Availability as prefilled syringes and nasal spray facilitates administration by family members or other caregivers; such treatment is not a substitute for emergency medical care.^{127 404 405} When administering naloxone outside of a supervised medical setting, always seek emergency medical assistance after the first dose is administered.¹²⁷

Many experts including CDC, American Heart Association (AHA), and American Society of Addiction Medicine recommend administration of naloxone in the event of a known or suspected opioid overdose.^{135 406 407}

The 2022 CDC clinical practice guideline on prescribing opioids for pain recommends that clinicians discuss the risk of opioid-related harms with patients, including risk mitigation strategies such as naloxone for overdose reversal.⁵⁰⁰

Clinicians should offer naloxone and provide overdose prevention education to patients receiving opioid analgesics who are at increased risk of opioid overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with a history of opioid or substance use disorder, those with medical conditions that could increase sensitivity to opioid effects, those who have experienced a prior opioid overdose, those taking higher dosages of opioids [e.g., ≥50 morphine mg equivalents/day, and those at risk of returning to a high dose to which they have lost tolerance [e.g., patients undergoing tapering or recently released from prison]).^{131 132 135 137 197 500 750} Naloxone also should be offered when patients receiving opioids have household members who are at risk for accidental ingestion or overdosage.⁷⁵⁰

Diagnosis of Suspected or Known Acute Opioid Overdosage

Used for diagnosis of suspected or known acute opioid overdosage.^{113 120}

Septic Shock

Naloxone hydrochloride injection is FDA-labeled for adjunctive use in the management of septic shock.^{113 120} Has been used in a limited number of patients in this setting.¹¹³ Rise in BP may last up to several hours, but not shown to improve survival and associated with adverse effects (e.g., agitation, nausea, vomiting, pulmonary edema, hypotension, cardiac arrhythmias, seizures).^{113 120}

Use caution in patients with septic shock, particularly in patients who may have underlying pain or previously received opioid therapy and may have developed opioid tolerance.^{113 120} Naloxone therapy is not included in the current Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock; fluid resuscitation and vasopressors (e.g., norepinephrine, vasopressin) are used first-line in hemodynamic management.¹³⁰

Diagnosis of Chronic Opioid Abuse (Naloxone Challenge Test)

To avoid precipitating opioid withdrawal following administration of naltrexone, naloxone has been used as a screening test (naloxone challenge test^{† [off-label]}) to document the absence of physiological dependence and reduce the risk of precipitated withdrawal.¹³⁵

The naloxone challenge test is not recommended in pregnant patients.¹³⁵

Combination Therapies

A combination of pentazocine hydrochloride and naloxone hydrochloride in a ratio of 100:1 is commercially available for oral use as an analgesic.¹¹⁵

Combinations of buprenorphine hydrochloride and naloxone hydrochloride in a ratio of 4:1 for sublingual administration or approximately 6:1 for intrabuccal administration are commercially available for use in the management of opioid dependence.^{114 133 134}

Opioid-Induced Pruritus

Prevention of opioid-induced pruritus^{† [off-label]} in children and adolescents.^{414 415}

Naloxone Hydrochloride Dosage and Administration

General

Patient Monitoring

• Carefully monitor patients who have responded to naloxone; the duration of action of most opioids may exceed that of naloxone and may result in recurrent respiratory and CNS depression.^{127 404 405} Administer repeated doses of naloxone when necessary.^{113 120 127 404 405}

• Monitor pediatric patients who have responded to naloxone for at least 24 hours.^{113 120 127 404 405}

• Monitor for development of opioid withdrawal symptoms (e.g., abdominal cramps, body aches, diarrhea, fever, increased blood pressure, nausea or vomiting, nervousness, runny nose, piloerection, restlessness or irritability, shivering or trembling, sneezing, sweating, tachycardia, weakness, yawning).^{113 120 127 404 405}

Other General Considerations

• Resuscitative measures such as maintenance of a patent airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary in the treatment of opioid overdose.¹¹³

• State naloxone laws vary, and may permit prescribing and dispensation to patients with risk factors for overdose or to lay persons (including nonmedical first responders, potential bystanders, and family and friends of opioid users).¹³⁹ Consult state law for further information.¹³⁹

• Carefully instruct patients and their family members or close contacts regarding clinical manifestations requiring naloxone administration, proper administration technique, and the importance of seeking emergency care immediately following administration of the initial dose.^{127 135 404 405} Advise caregivers, household members, and other close contacts of where naloxone is stored, and to ensure the location is easily accessible during an emergency (e.g., naloxone should not be stored in a locked container with the opioid).⁷⁵⁰

• Advise patients taking doses of opioid analgesics when away from home to carry naloxone with them and to advise individuals who are with them of the availability of the drug and its proper use.⁷⁵⁰

Administration

Administer by IV, sub-Q, or IM injection; by IV infusion; or intranasally.^{113 120 127 404 405}

The most rapid onset of action is achieved by IV administration, which is recommended in emergency situations in medically supervised settings.^{113 120} Because absorption may be erratic or delayed, AAP does not endorse sub-Q or IM injection for emergency medical management of opioid intoxication in children or neonates.^{110 113 120}

When IV access cannot be established in emergency situations, has been administered via an endotracheal tube^{† [off-label]412} and by intraosseous^{† [off-label]} (IO) injection.⁴¹²

IV Infusion

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 opioids are being antagonized.⁴⁰⁶

Dilution

For continuous IV infusion, manufacturers state to dilute 2 mg of naloxone hydrochloride in 500 mL of 0.9% sodium chloride or 5% dextrose injection to produce a solution containing 0.004 mg/mL (4 mcg/mL).^{113 120} Other concentrations have been recommended(see Standardize 4 Safety under Dosage and Administration).²⁴⁹

Rate of Administration

Titrate in accordance with patient’s response.^{113 120}

IM or Sub-Q Injection

May be administered by family members or other caregivers prior to emergency medical response to individuals with known or suspected opioid overdosage.⁴⁰⁴ Caregivers should seek emergency medical care immediately after administering the initial dose.⁴⁰⁴

May be administered by IM or sub-Q injection via prefilled syringes.^{113 120 404} Administer initial dose of naloxone prefilled syringes (Zimhi) IM or sub-Q into the anterolateral aspect of the thigh, through clothing if necessary.⁴⁰⁴ When administered to pediatric patients <1 year of age, pinch the thigh muscle while administering the drug.⁴⁰⁴

Intranasal Administration

May be administered by family members or other caregivers prior to emergency medical response to individuals with known or suspected opioid overdosage.^{127 405}

Do not remove nasal spray units from carton until time of administration; do not prime or test units prior to administration.^{127 405}

Intranasal Administration Technique

Place the patient in a supine position.^{127 405} Remove the nasal spray unit from carton and blister package.^{127 405} Tilt patient’s head back, with one hand supporting the neck.^{127 405} Do not prime or test device prior to administration.^{127 405} Gently insert tip of nasal spray unit into one nostril until the fingers on either side of the nozzle are against the patient's nose; press device plunger firmly to administer dose.^{127 405}

Remove nozzle from nostril following administration, and place patient in recovery position; closely monitor patient.⁴⁰⁵

If additional doses are required, administer into alternate nostrils using new nasal spray unit.^{127 405}

Standardize 4 Safety

Standardized concentrations for IV naloxone have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.^{249 250} Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.^{249 250} For additional information on S4S (including updates that may be available), see [Web].^{249 250}

The panel recognizes that 40 and 400 mcg/mL concentrations listed in the pediatric standards are 10× different; however, these are the only two concentrations studied for stability.²⁴⁹

Dosing units differ from concentration units

Dosage

Available as naloxone hydrochloride; dosage expressed in terms of the salt.^{113 120 127 404 405}

Pediatric Patients

Opioid-induced Depression in Neonates

IV, IM, or Sub-Q

Usual initial dose is 0.01 mg/kg, administered at 2- to 3-minute intervals to the desired degree of reversal.^{113 120}

Opioid Overdosage in Children

IV, IM, or Sub-Q

Children may receive an initial IV naloxone hydrochloride dose of 0.01 mg/kg; if this dose does not produce the desired degree of response, a subsequent dose of 0.1 mg/kg may be administered.^{113 120}

Intranasal

One spray (2, 4, or 8 mg [contents of one spray unit]); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary (if additional spray units available) at 2- to 3-minute intervals until emergency care arrives.^{127 405} Prescribe the 2-mg strength for opioid-dependent patients expected to be at risk for severe opioid withdrawal only when the risk for accidental or intentional opioid exposure by household contacts is low.¹²⁷

IO^† or Endotracheal^†

Children <5 years of age or weighing ≤20 kg: Some experts suggest dose of 0.1 mg/kg.⁴⁰³

Children ≥5 years of age or weighing >20 kg: Some experts suggest dose of 2 mg.⁴⁰³

Optimum dose for administration via an endotracheal tube^† not established (higher doses as compared with other routes may be necessary).⁴⁰³

Diagnosis of Opioid Overdosage

IV

No specific recommendations at this time.^{113 120 127 404 405} If no response observed after administration of 10 mg of naloxone, diagnosis of opioid-induced toxicity should be questioned.^{113 120}

Postoperative Opioid Depression

IV

For initial reversal of respiratory depression, naloxone hydrochloride should be administered in increments of 0.005–0.01 mg at 2- to 3-minute intervals until desired response (i.e., adequate ventilation and alertness without substantial pain or discomfort) is obtained.^{113 120}

Treatment of Opioid-Induced Pruritus

IV†

Dosages in children and adolescents ranged from 0.25–1.0 mcg/kg per hour via continuous IV infusion.^{414 416}

Adults

Postoperative Opioid 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 opioid administered.^{113 120}

For continuous IV infusion, titrate rate of infusion in accordance with the patient’s response.^{113 120}

Opioid Overdosage

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.^{113 120}

Duration of opioid action often exceeds that of naloxone; opioid depressant effects may return as the effects of naloxone diminish, and additional naloxone doses may be required.^{113 120 127 404 405}

Carefully monitor patient for recurrence of opioid depressant effects.^{113 120 127 404 405}

IM or Sub-Q

2 mg (contents of one prefilled syringe) or 5 mg (contents of one prefilled syringe; Zimhi); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary at 2- to 3-minute intervals until emergency care arrives.^{113 404}

Intranasal

One spray (2, 4, or 8 mg [contents of one spray unit]); if patient fails to respond or responds but subsequently relapses into respiratory depression, repeat as necessary at 2- to 3-minute intervals until emergency care arrives.^{127 405} Prescribe the 2-mg strength for opioid-dependent patients expected to be at risk for severe opioid withdrawal only when the risk for accidental or intentional opioid exposure by household contacts is low.¹²⁷

IO† or Endotracheal†

Optimal dosage not established; typical dose given by the endotracheal route is 2–2.5 times the recommended IV dose.⁴¹⁶

Diagnosis of Opioid Overdosage

IV

No specific recommendations at this time.^{113 120 127 404 405} If no response observed after administration of 10 mg of naloxone, diagnosis of opioid-induced toxicity should be questioned.^{113 120}

Naloxone Challenge Test

Administration of naloxone hydrochloride 0.4–0.8 mg before initiating treatment with naltrexone may assist in documenting the absence of physiological dependence and minimizing the risk for withdrawal.¹³⁵

Septic Shock

IV

Optimal dosage and treatment regimens not established.^{113 120}

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{113 120 127 404 405}

Renal Impairment

No specific dosage recommendations.^{113 120}

Geriatric Patients

No specific dosage recommendation; use caution when selecting dosage.^{113 120 127 404 405}

Cautions for Naloxone Hydrochloride

Contraindications

• Known hypersensitivity to the drug or any ingredient in the formulation.^{113 120 127 404 405}

Warnings/Precautions

Other Resuscitative Measures

When used in management of acute opioid 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.^{113 120 127 404 405}

Excessive Doses in Postoperative Patients

Excessive doses in postoperative patients have resulted in agitation and reversal of analgesia.^{113 120 127 404 405}

Use in Patients with Cardiovascular Disorders

Hypotension, hypertension, ventricular tachycardia/fibrillation, pulmonary edema, and cardiac arrest reported in postoperative patients receiving naloxone, sometimes resulting in death, coma, or encephalopathy.^{113 127} Reported mainly in patients with preexisting cardiovascular disorders or receiving other drugs with similar adverse cardiovascular effects.^{113 127}

Use with caution in patients with preexisting cardiovascular disease or in those receiving potentially cardiotoxic drugs; monitor such patients for hypotension, ventricular tachycardia or fibrillation, and pulmonary edema.^{113 127}

Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists

Reversal of respiratory depression resulting from overdosage of opioid partial agonists (e.g., buprenorphine, pentazocine) may be incomplete and require higher or repeated doses of naloxone.^{113 120 127 404 405}

Precipitation of Severe Opioid Withdrawal

May precipitate severe opioid withdrawal symptoms.^{113 120 127 404 405} Abrupt postoperative reversal of opioid effects may result in nausea, vomiting, sweating, tremor, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia/ fibrillation, pulmonary edema, and cardiac arrest, which may result in death.^{113 120 127 404 405}

Administer with caution to patients known or suspected to be physically dependent on opioids (including neonates born to women who are opioid dependent), particularly in patients with cardiovascular disease.^{113 120 127 404 405} (See Use in Patients with Cardiovascular Disorders under Cautions.)

Risk of Recurrent Respiratory and CNS Depression

Duration of action of most opioids may exceed that of naloxone resulting in a return of respiratory and/or CNS depression after an initial improvement.^{113 120 127 404 405} Monitor patients closely and administer repeated doses of naloxone when necessary.^{113 120 127 404 405} Patients with life-threatening overdosage of a long-acting or extended-release opioid may require longer periods of observation.¹⁹⁶ Monitor pediatric patients who have responded to naloxone for at least 24 hours.^{113 120 127 404 405}

Risk of Accidental Needlestick Injury

A needlestick injury could occur in emergency situations with use of naloxone prefilled syringes (Zimhi).⁴⁰⁴ If an accidental needlestick occurs, seek medical attention.⁴⁰⁴ Stress to patients the importance of familiarizing themselves with the device prior to emergency situation.⁴⁰⁴

Specific Populations

Pregnancy

Limited data on use in pregnant women.^{113 120 127 404 405} Use only when clearly needed.^{113 120 127 404 405} Consider risk-benefit ratio before administering naloxone to a pregnant woman with known or suspected opioid dependence.^{113 120} Naloxone crosses the placenta; risk of opioid withdrawal in both the pregnant woman and fetus.^{113 120 127 405} Monitor for fetal distress.^{113 120 127 404}

Lactation

Not known whether naloxone is distributed into milk or has any effect on the breast-fed infant or on milk production, use naloxone with caution in nursing women.^{113 120 127 404 405} Does not affect prolactin or oxytocin concentrations in nursing women, and oral bioavailability is minimal.^{127 404 405}

Females and Males of Reproductive Potential

Animal studies revealed no evidence of impaired fertility.^{127 404 405}

Pediatric Use

Naloxone may be used to reverse effects of opioids in infants and children.^{113 120 127 404 405} Safety and efficacy of prefilled syringes for IM or Sub-Q use (Zimhi) or nasal spray (e.g., Narcan, Kloxxado) established in pediatric patients of all ages for emergency treatment of known or suspected opioid overdosage.^{127 404 405} Such use in pediatric patients supported by adult bioequivalence studies and evidence from other naloxone products.^{127 404 405}

Absorption following intranasal administration or IM or sub-Q injection in pediatric patients may be erratic or delayed; carefully monitor pediatric patients ≥24 hours.^{113 120 127 404 405}

Safety and efficacy in management of hypotension associated with septic shock not established in pediatric patients.^{113 120} In a study of 2 neonates with septic shock, treatment with naloxone produced positive pressor response; however, one patient subsequently died after intractable seizures.^{113 120}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{113 120 127 404 405} Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.^{113 120 127 404 405}

Hepatic Impairment

Safety and efficacy not established; use with caution.^{113 120}

Renal Impairment

Safety and efficacy not established; use with caution.^{113 120}

Common Adverse Effects

Intranasal naloxone: abdominal pain, asthenia, dizziness, headache, increased blood pressure, constipation, toothache, muscle spasms, musculoskeletal pain, nasal congestion, nasal discomfort, nasal dryness, nasal edema, nasal inflammation, presyncope, rhinalgia, xeroderma.^{127 405}

Parenteral naloxone (postoperative use): Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest reported; sequelae include death, coma, and encephalopathy.^{113 120} Cardiovascular effects most common in patients with preexisting cardiovascular disease or in those receiving other drugs that produce similar adverse cardiovascular effects.^{113 120}

Naloxone injection for IM or sub-Q use (Zimhi): dizziness, elevated bilirubin, lightheadedness, and nausea.⁴⁰⁴

Abrupt reversal of opiate effects may precipitate acute withdrawal and aggressive behavior.^{113 120}

Drug Interactions

Metabolized in the liver primarily by glucuronide conjugation.^{113 120 127 404 405}

Specific Drugs

Naloxone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly inactivated following oral administration.¹³⁵

Prefilled syringes (Zimhi): IM administration of 5-mg dose provided significantly higher peak plasma concentration and AUC compared to a single IM injection of 2 mg naloxone hydrochloride.⁴⁰⁴

Naloxone nasal spray (Narcan): Time to peak plasma concentration similar to that observed following IM injection.¹²⁷ Dose-normalized bioavailability approximately 43–54% that of IM dose.¹²⁷ Peak plasma concentrations and AUC substantially higher following intranasal administration of a 2-mg dose as a single spray in one nostril (approximately 3.3- and 2.6-fold higher, respectively), a 4-mg dose as a single spray in one nostril (approximately 5.5- and 4.4-fold higher, respectively), a 4-mg dose as one 2-mg spray in each nostril (approximately 7.2- and 5.4-fold higher, respectively), or an 8-mg dose as one 4-mg spray in each nostril (approximately 11- and 8.7-fold higher, respectively) compared with a 0.4-mg IM dose.¹²⁷

Kloxxado nasal spray: Time to peak plasma concentration with 8-mg single spray similar to that observed following IM injection of a 0.4-mg dose.⁴⁰⁵ Dose-normalized bioavailability relative to that of IM injection ranged from 42–47%.⁴⁰⁵

Onset

IV: Within 1–2 minutes.^{113 120 404}

Sub-Q or IM: Within 2–5 minutes.^{113 120 404}

Duration

Depends on the dose and route of administration and is more prolonged following IM than IV administration.^{113 120}

Distribution

Extent

Parenteral: Rapidly distributed into body tissues and fluids.^{113 120 127 404 405}

Readily (within 2 minutes) crosses the placenta.^{113 120 127 404 405}

Unknown whether distributed into breast milk.^{113 120 127 404 405}

Plasma Protein Binding

Weakly bound to plasma proteins (mainly albumin).^{113 120 127 404 405}

Elimination

Metabolism

Rapidly metabolized in the liver, principally by conjugation with glucuronic acid.^{113 120 127 404 405}

Major metabolite is naloxone-3-glucuronide.^{113 120 127 404 405}

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.^{113 120 127 404 405}

Half-life

Naloxone injection in adults: 30–81 minutes.^{113 120}

Naloxone injection in neonates: About 3 hours.^{113 120}

Zimhi injection: 1.2–1.9 hours.⁴⁰⁴

Narcan nasal spray: 1.9–2.1 hours.¹²⁷

Kloxxado nasal spray: 1.8–2.7 hours.⁴⁰⁵

Stability

Storage

Parenteral

Injection

Vials and ampuls: 20–25°C; protect from light.^{113 120}

Zimhi prefilled syringes: 20–25°C; excursions permitted to 15–30°C.⁴⁰⁴ Protect from light.⁴⁰⁴ Do not refrigerate.⁴⁰⁴

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.^{113 120}

Intranasal Preparations

Narcan Nasal spray: 15–20°C; excursions permitted to temperatures up to 40°C.¹²⁷ Do not freeze.¹²⁷ Protect from light.¹²⁷ If nasal spray freezes the device will not spray; if this occurs, do not wait for nasal spray to thaw and seek emergency medical help immediately.¹²⁷ Naloxone nasal spray may still be used if it has been thawed after previously being frozen.¹²⁷

Kloxxado nasal spray: 20–25°C; excursions permitted to 5–40°C.⁴⁰⁵ Do not freeze.⁴⁰⁵ Protect from light.⁴⁰⁵ If nasal spray freezes the device will not spray; if this occurs, do not wait for nasal spray to thaw and seek emergency medical help immediately.⁴⁰⁵ Naloxone nasal spray may still be used if it has been thawed after previously being frozen.⁴⁰⁵

Actions

• Opioid antagonist.^{113 120 127 404 405}

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

• Because the duration of action of naloxone is generally shorter than that of the opioid, the effects of the opioid may return as the effects of naloxone dissipate.^{113 120 127 404 405}

• Does not produce tolerance or physical or psychological dependence.^{113 120}

• It is thought to act as a competitive antagonist at µ, κ, and σ opioid receptors in the CNS; it is thought that the drug has the highest affinity for the μ receptor.^{113 127}

Advice to Patients

• Advise patients, family members, and caregivers to read the FDA-approved patient labeling and to become familiar with all information related to appropriate administration of the provided naloxone formulation.^{127 404 405}

• Instruct patients and family members or close contacts regarding clinical manifestations requiring naloxone administration, proper administration technique, and the importance of seeking emergency care immediately following administration of the initial dose.^{113 120 127 135 404 405}

• Advise caregivers, household members, and other close contacts of where naloxone is stored, and to ensure the location is easily accessible during an emergency (e.g., naloxone should not be stored in a locked container with the opioid).750,

• Instruct patients and their family members or caregivers on recognition of signs and symptoms of opioid overdose (e.g., extreme somnolence, respiratory depression, miosis, bradycardia, hypotension).^{127 404 405}

• Advise patients of the risk of recurrent respiratory and CNS depression, and to seek immediate emergency medical assistance after the first dose of naloxone and to continually monitor the patient.^{127 404 405}

• Advise patients of the potential limited efficacy of naloxone administration when used to reverse respiratory depression caused by partial agonists or mixed agonists/antagonists such as buprenorphine and pentazocine, and that higher doses or additional administration of naloxone may be required.^{127 404 405}

• Instruct patients that administration of naloxone in patients who are opioid-dependent may precipitate severe opioid withdrawal accompanied by symptoms such as body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and hypertension.^{127 404 405} Instruct patients that opioid withdrawal may be life-threatening in neonates if not recognized and properly treated; instruct patients on these signs and symptoms (e.g., convulsions, excessive crying, hyperactive reflexes).^{127 404 405}

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.^{127 404 405}

• Advise women to inform clinicians if they are or plan to become pregnant or plan to breast-feed.⁴⁰⁴

• Inform patients of other important precautionary information.^{127 404 405}

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

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