Naloxone information from DrugsUpdate  

Pharmacodynamics

Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system. Naloxone is a μ-opioid receptor competitive antagonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- and δ-opioid receptors.

Pharmacokinetics

Naloxone is a pure opioid antagonist that acts competitively at opioid receptors.
Onset
2 min (IV); 2-5 min (endotracheal, IM, SC).

Duration
30-120 min depending on route; IV has a shorter duration than IM.

Distribution: Crosses placenta.

Metabolism
Extensively hepatic via glucuronidation.

Excretion
Urine (as metabolites); elimination half-life: 0.5-1.5 hr (adult); 3-4 hr (neonates).

Naloxone Indications / Naloxone Uses

Information Not Available

Naloxone Adverse Reactions / Naloxone Side Effects

Occur secondarily to reversal (withdrawal) of narcotic analgesia and sedation. Mental depression, apathy, inability to concentrate, sleepiness, irritability, anorexia, nausea, and vomiting in high oral doses during initial treatment of opiate addiction.

Potentially Fatal: Severe cardiopulmonary effects (e.g. hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnoea, pulmonary oedema, cardiac arrest) in postoperative patients, most frequently in those with preexisting CV disease. Recurrence of respiratory depression in long-acting opioids.

Precautions

In addition to Naloxone, other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary to counteract acute narcotic poisoning.

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been reported. These have occurred in postoperative patients, most of whom had pre-existing cardiovascular disorders or received other drugs which may have similar adverse cardiovascular effects. Although a direct cause-and-effect relationship has not been established, Naloxone should be used with caution in patients with pre-existing cardiac disease or patients who have received potentially cardiotoxic drugs.

Special Precautions

Patients physically dependent on opioids, or who have received large doses of opioids (acute withdrawal syndrome may be precipitated). Pregnancy and lactation.

Other Drug Interactions

Decreased effect of opioid analgesics.

Potentially Fatal: Acute withdrawal reaction in physically dependent patients may occur with opioid analgesics. Severe cardiopulmonary effects may occur with cardiotoxic drugs.

Other Interactions

Information Not Available

Dosage

Oral
Opioid dependence
Adult: As hydrochloride: 200 mg to 3 g daily.

Intravenous
Opioid overdosage
Adult: As hydrochloride: 0.4-2 mg repeated if necessary at 2-3 min intervals. If there is no response after a total of 10 mg has been given, consider the possibility of overdosage with other drugs. Reduce dose for opioid-dependent patients: 0.1-0.2 mg. IM/SC routes may be used (at IV doses) if IV admin is not feasible.
Child: As hydrochloride: Initially 10 mcg/kg IV followed by 100 mcg/kg IV if necessary. Alternatively, 0.4-0.8 mg IM or SC, repeated as necessary, if IV admin is not feasible.

Intravenous
Reversal of central depression from opioid use during surgery
Adult: As hydrochloride: 100-200 mcg at intervals of 2-3 minute, titrate dose according to response while maintaining analgesia.
Child: As hydrochloride: 5-10 mcg IV at 2-3 min intervals.

Parenteral
Opioid-induced depression in neonates due to obstetric analgesia
Child: As hydrochloride: 10 mcg/kg IV, IM or SC repeated at 2-3 min intervals if necessary or 60 mcg/kg as a single IM dose.

Reconstitution
Stable in 0.9% sodium chloride and 5% dextrose inj at 4 mcg/ml for 24 hr.

Incompatibility
Preparations containing bisulfite, metabisulfite, long-chain or high-molecular wt anions, or solutions with an alkaline pH.

Food(before/after)

Information Not Available

Naloxone and Pregnancy

Caution when used during pregnancy.

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Naloxone and Lactation

 Caution when used during lactation

Naloxone and Children

Narcotic Overdose—Known or Suspected
The usual initial dose in children is 0.01 mg/kg body weight given I.V. If this dose does not result in the desired degree of clinical improvement, a subsequent dose of 0.1 mg/kg body weight may be administered. If an I.V. route of administration is not available, Naloxone may be administered I.M. or S.C. in divided doses. If necessary, Naloxone hydrochloride injection can be diluted with sterile water for injection.

Postoperative Narcotic Depression
Follow the recommendations and cautions under "Adult Postoperative Depression." For the initial reversal of respiratory depression Naloxone hydrochloride should be injected in increments of 0.005 mg to 0.01 mg intravenously at two- to three-minute intervals to the desired degree of reversal.

Naloxone and Geriatic

Information Not Available

Naloxone and Other Contraindications

Hypersensitivity

Storage

Intravenous
Store at 25°C. Protect from light.

Oral
Store at 25°C. Protect from light.

Parenteral
Store at 25°C. Protect from light.

Lab interference

Intravenous
Store at 25°C. Protect from light.

Oral
Store at 25°C. Protect from light.

Parenteral
Store at 25°C. Protect from light.