Naloxane

Uses

Naloxane is used for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids, including propoxyphene, methadone and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine, butorphanol, and cyclazocine. Naloxane is also used for diagnosis of suspected or known acute opioid overdosage. Naloxane may be useful as an adjunctive agent to increase blood pressure in the management of septic shock

Naloxane is also used to associated treatment for these conditions: Opioid Dependence, Opioid Overdose, Pruritus, Respiratory Depression, Septic Shock, Severe Pain, Moderate Pain, Suspected Opioid Overdose

How Naloxane works

Naloxane is a competitive inhibitor of the µ-opioid receptor. Naloxane antagonizes the action of opioids, reversing their effects. If a patient has not taken opioids, naloxone does not have a significant effect on patients.

Dosage

Naloxane dosage

Reversal of central depression from opioid use during surgery:

• Adult:100-200 mcg at intervals of 2-3 minute, titrate dose according to response while maintaining analgesia.
• Child:5-10 mcg IV at 2-3 min intervals.

Opioid overdosage:

• Adult: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: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.

Opioid-induced depression in neonates due to obstetric analgesia:

• Child:10 mcg/kg IV, IM or SC repeated at 2-3 min intervals if necessary or 60 mcg/kg as a single IM dose.

Intravenous:

• Reversal of central depression from opioid: Stable in 0.9% sodium chloride and 5% dextrose inj at 4 mcg/ml for 24 hr.
• Opioid overdosage: Stable in 0.9% sodium chloride and 5% dextrose ing at 4 mcg/ml for 24 hr.

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

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.

Toxicity

If a patient has not taken opioids, naloxone does not have a significant effect on patients.

The oral LD₅₀ in mice and rats is >1 g/kg. The intraperitoneal LD₅₀ is 80 mg/kg in mice and 239 mg/kg in rats. The subcutaneous LD₅₀ is 286 mg/kg in mice and 500 mg/kg in rats.

Precaution

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

Interaction

Decreased effect of opioid analgesics.

Food Interaction

• Take separate from meals. When formulated as a buccal film or sublingual form, avoid eating or drinking until the film has completely dissolved.

Naloxane Drug Interaction

Moderate: hydromorphone, morphine, oxycodoneUnknown: aspirin, epinephrine, lorazepam, diphenhydramine, duloxetine, glucose, furosemide, pregabalin, metoprolol, acetaminophen, promethazine, acetaminophen, diazepam, cyanocobalamin, ascorbic acid, cholecalciferol, ondansetron

Naloxane Disease Interaction

Major: CV disordersModerate: liver disease, renal, septic shock

Volume of Distribution

The volume of distribution of naloxone is 200 L. Naloxane distributes into tissues rapidly. It can also cross the placenta and blood-brain barrier.

Elimination Route

An intranasal dose of naloxone is 42-47% bioavailable. An 8 mg dose of nasal naloxone reaches a C_max of 12.3-12.8 ng/mL, with a T_max of 0.25 hours, and an AUC of 16.7-19.0 h*ng/mL. A 0.4 mg intramuscular dose reaches a C_max of 0.876-0.910 ng/mL, with a T_max of 0.25 hours, and an AUC of 1.94-1.95 h*ng/mL. A 2 mg intravenous dose reaches a C_max of 26.2 ng/mL with an AUC of 12.8 h*ng/mL.

Half Life

The mean half life of naloxone hydrochloride is 1.8-2.7 hours intranasally, 1.4 hours intramuscularly, and 1.2 hours intravenously. In neonates, the mean half life is 3.1 ± 0.5 hours.

Clearance

The clearance of naloxone is 2500 L/day.

Elimination Route

After oral or intravenous administration, naloxone is 25-40% eliminated in the urine within 6 hours, 50% in 24 hours, and 60-70% in 72 hours. The metabolites naloxone-3-glucuronide, noroxymorphone, and naloxol are all detected in the urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Storage Condition

Store at 25° C. Protect from light.

Innovators Monograph

You find simplified version here Naloxane