DrugindexOnline^{2nd edition}

Pronouncation: (NAL-ox-ohn HIGH-droe-KLOR-ide)
Class: Antidote

Trade Names:
Naloxone Hydrochloride
- Neonatal injection 0.02 mg/mL

Trade Names:
Narcan
- Injection 0.4 mg/mL

Mechanism of Action

Pharmacology

Evidence suggests that naloxone antagonizes opioid effects by competing for opiate receptor sites in the CNS.

Pharmacokinetics

Distribution

Rapidly distributed in the body and readily crosses the placenta. Plasma protein binding is relatively weak.

Metabolism

Metabolized in the liver primarily by glucuronidation (major metabolite naloxone-3-glucuronide).

Elimination

In adults the t _½ ranges from 30 to 81 min, while in neonates the t _½ is about 3 hr. Approximately 25% to 40% is excreted as metabolites in the urine within 6 hr, about 50% in 24 hr, and 60% to 70% in 72 hr.

Onset

Following IV administration, the onset of action is usually apparent within 2 min.

Duration

Duration of effect is more prolonged after IM injection compared with IV administration.

Indications and Usage

Complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids, including propoxyphene; diagnosis of suspected or known opioid overdosage; adjunctive agent to increase BP in management of septic shock.

Contraindications

Standard considerations.

Dosage and Administration

Opioid-induced Depression
Neonates

IV/IM/SC 0.01 mg/kg. Dose may be repeated in accordance with adult administration guidelines for postoperative opioid depression.

Opioid Overdosage
Adults

IV ( IM/SC if IV route is not available) 0.4 to 2 mg; dose may be repeated at 2 to 3 min intervals if desired degree of counteraction and improvement in respiratory function are not obtained. If no response is observed after administration of 10 mg of naloxone, question the diagnosis.

Children

IV ( IM/SC if IV route is not available) Initial dose is 0.01 mg/kg; may give a subsequent dose of 0.1 mg/kg.

Postoperative Opioid Depression
Adults

IV Small doses are usually sufficient. Titrate dose in increments of 0.1 to 0.2 mg IV at 2- to 3-min intervals to the desired degree of reversal (eg, adequate ventilation without significant pain). Repeat doses may be required at 1- or 2-hr intervals, depending on amount, type, and time interval since last administration of an opiate.

Children

IV Inject in increments of 0.005 to 0.01 mg at 2- to 3-min intervals to the desired degree of reversal of respiratory depression. Follow recommendation and cautions for adults.

Septic Shock
Adults

Optimal dose and duration of treatment of hypotension in septic shock have not been established.

General Advice

• For IV, IM, or SC injection.
• Dilute prescribed dose in normal saline or 5% dextrose solution for IV infusion.
• Do not administer if particulate matter, cloudiness, or discoloration noted.
• Discard any unused solution in single-dose ampule. Do not save for future use.

Storage/Stability

Store vials and ampules at controlled room temperature (59°F to 86°F). Protect from light. Use diluted solution for infusion within 24 hr. Discard any unused infusion solution after 24 hr.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension; hypertension; ventricular tachycardia and fibrillation; pulmonary edema; cardiac arrest; death.

CNS

Agitation; seizures; convulsions; paresthesia; hallucinations; tremulousness.

Dermatologic

Sweating; injection site reactions; flushing.

GI

Nausea; vomiting.

Respiratory

Dyspnea; respiratory depression; hypoxia.

Miscellaneous

Coma; encephalopathy; withdrawal.

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

May be given IV/IM/SC in children and neonates to reverse the effects of opiates. IM/SC route for opiate intoxication is not endorsed by the American Academy of Pediatrics because absorption may be erratic or delayed. Safety and efficacy in septic shock not established. It is preferable to administer directly to the neonate if needed after delivery.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Opiate duration

Because duration of action of some opiates may exceed that of naloxone, keep patients under continuous surveillance.

Postoperative

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased BP, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest, which may result in death.

Withdrawal

Use with caution in patients, including neonates of mothers suspected to be physically dependent on opioids because an acute withdrawal syndrome may be precipitated.

Overdosage

Symptoms

Seizures, severe hypertension, bradycardia, cognitive impairment, behavioral symptoms (including irritability, anxiety, tension, suspiciousness, sadness, difficulty concentrating, lack of appetite), somatic symptoms (including dizziness, heaviness, sweating, nausea, stomachaches).

Patient Information

• Explain name, action, and potential side effects of drug.
• Advise patient or caregiver that medication will be prepared and administered by a health care professional in a medical setting.