Naloxone Hydrochloride

Pronunciation: NAL-ox-ohn HIGH-droe-KLOR-ide
Class: Antidote

Trade Names

Naloxone Hydrochloride
- Injection, solution 0.04 mg/mL
- Injection, solution 1 mg/mL

Pharmacology

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

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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 glucuronide conjugation (major metabolite naloxone-3-glucuronide).

Elimination

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

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, methadone, and certain narcotic-antagonist analgesics (eg, nalbuphine, pentazocine, and butorphanol); diagnosis of suspected or known opioid overdosage; adjunctive agent to increase BP in management of septic shock.

Contraindications

Hypersensitivity to naloxone.

Dosage and Administration

IV/IM/Subcutaneous 0.01 mg/kg. Dose may be repeated in accordance with adult administration guidelines for postoperative opioid depression. When using in neonates, a product containing naltrexone 0.02 mg/mL should be used.

IV Use IM/subcutaneous if IV route is unavailable. 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.

IV Use IM/subcutaneous if IV route is unavailable. Initial dose is 0.01 mg/kg; may give a subsequent dose of 0.1 mg/kg.

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-h intervals, depending on amount, type, and time interval since last administration of an opiate. Supplemental IM doses have been shown to produce a longer-lasting effect.

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 (eg, adequate ventilation without significant pain). Repeat doses may be required at 1- or 2-h intervals, depending on amount, type, and time interval since last administration of an opiate.

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

General Advice

• For IV, IM, or subcutaneous injection; most rapid onset of action is by IV administration injection.
• Dilute prescribed dose in sodium chloride 0.9% injection. If necessary, naloxone can be diluted with sterile water for injection or 5% dextrose. The addition of naloxone 2 mg in 500 mL provides a concentration of 0.004 mg/mL.
• Do not administer if particulate matter, cloudiness, or discoloration noted.
• Do not mix with bisulfite, metabisulfite, long-chain or high molecular weight anions or any solution having an alkaline pH.
• Titrate the rate of administration in accordance with the patient's response.

Storage/Stability

Store between 59°F and 86°F. Protect from light. Use diluted solution for infusion within 24 h. Discard any unused infusion solution after 24 h.

Drug 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/Subcutaneous in children and neonates to reverse the effects of opiates. IM/Subcutaneous 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.

Special Risk Patients

Use with caution in patients with preexisting cardiac disease or in patients receiving potentially cardiotoxic drugs.

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, hypertension/hypotension, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest, which may result in death.

Respiratory depression

Not effective against respiratory depression due to nonopioid drugs; reversal of buprenorphine-induced respiratory depression may be incomplete.

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

• Advise patient or caregiver that medication will be prepared and administered by a health care professional in a medical setting.

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