DESCRIPTION

Naloxone and nalmefene are narcotic antagonists.

FORMS AND USES

• Substances include naloxone (Narcan) and nalmefene (Revex).
• These drugs are used for the reversal of narcotic toxicity.
  • Naloxone hydrochloride is available in 0.02, 0.4, and 1.0 mg/ml injectable form.
  • Nalmefene is available in 0.1- or 1.0-mg concentrations.

MECHANISM OF ACTION

• These drugs compete and displace opioid drugs from µ, kappa-, and sigma- opioid receptors, thereby reversing the effect of narcotic administration.
• Neither drug has agonist activity.
• At lower doses, naloxone and nalmefene have clinically indistinguishable durations of action.
• At higher doses, nalmefene has a longer duration; activity may extend up to 8 hours after a 2-mg dose.

DRUG AND DISEASE INTERACTIONS

• Naloxone and nalmefene prevent action of all opioid drugs.
• Patients may develop agitation, hypertension, or ventricular irritability when sympathomimetic drugs are also present.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category B. Animal studies indicate no fetal risk, and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in pregnant women do not.
• Withdrawal may be precipitated in unborn children when the mother receives naloxone during labor.
• Narcotic antagonists should be used during pregnancy only when the mother's life is endangered by opioid toxicity.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Altered mental status of undetermined etiology
• Respiratory depression from known opioid overdose
• CNS depression from known opioid overdose without respiratory depression
  • When treating known heroin overdose, it may be prudent to observe those patients who can maintain their airway and oxygenation rather than to treat them with naloxone.
  • This may allow discharge of the patient without the concern of recurrent opioid toxicity or withdrawal.
• Reversal of opioid anesthesia
• Clonidine intoxication. Conflicting evidence exists concerning use of naloxone for clonidine intoxication, and it is not routinely recommended.

Known hypersensitivity to naloxone or nalmefene contraindicates their use.

ADVERSE EFFECTS

• Withdrawal can occur in opioid-dependent patients.
• Withdrawal seizures in neonates of opioid-dependent mothers may be life threatening.
• Noncardiogenic pulmonary edema occurs rarely.
  • High-dose opioid administration may reverse the pulmonary edema
  • Generally, supportive care is sufficient.

ALTERED MENTAL STATUS OF UNDETERMINED ETIOLOGY

Naloxone

• Dose in adult or pediatric patients is 2.0 to 10.0 mg administered intravenously in 2.0-mg increments.
• If no response is observed after each 2.0-mg bolus, another 2.0 mg may be administered.
• A cumulative dose of 10 to 20 mg may be needed for intoxication with propoxyphene, nalbuphine, or butorphanol.
• Although these routes are less desirable, naloxone also may be administered by endotracheal, intramuscular, intralingual, intraosseous, or subcutaneous injection as circumstances demand.
• If reversal response occurs, patients should be observed for 4 hours after final dose; repeat bolus doses may be needed.
• A patient with persistent or recurrent effects may be treated with constant infusion of naloxone; naloxone should be mixed in D5W and administered at a rate that delivers two thirds of the initially effective bolus dose per hour, titrated to effect.

Nalmefene

• Patient can receive a cumulative dose of 0.5 to 1.5 mg.
• The recommended starting dose of 0.5 mg should be administered as an intravenous push; if the patient exhibits no response, an additional 1 mg should be given. However, some practitioners start with a dose of 1.0 mg followed by another dose of 1.0 mg, if needed.
• Higher doses of nalmefene appear to give prolonged activity; 1.5 mg of nalmefene was effective in blocking opioid activity up to 8 hours.
• If repeat dosing is required, the patient should be admitted.
• Nalmefene may be administered by intravenous, intramuscular, or subcutaneous administration. The dose is the same, but onset of effect may be delayed 10 to 15 minutes.

RESPIRATORY DEPRESSION FROM KNOWN OPIOID OVERDOSE

• Naloxone is the first choice; 2.0 to 10.0 mg is administered in 2.0-mg increments.
• A cumulative dose of 10 to 20 mg may be needed for propoxyphene, nalbuphine, or butorphanol, administered as described for altered mental status above.
• Nalmefene is effective but difficult to use appropriately unless the patient's likelihood of dependency is known; it should be administered as described above for altered mental status.

CNS DEPRESSION FROM KNOWN OPIOID OVERDOSE WITHOUT RESPIRATORY DEPRESSION

• Because time is less urgent, smaller doses (with lower risk of producing florid withdrawal) may be used.
• Treatment should begin with a bolus dose of naloxone of 0.1 to 0.4 mg, escalating to typical 2.0-mg dose as described for altered mental status above, if needed.

REVERSAL OF OPIOID ANESTHESIA

If anesthesia has resulted in depression of respiratory or CNS function, 0.4 to 2.0 mg naloxone can be administered in an intravenous push as dictated by the urgency of the situation. If serious respiratory depression has developed, the initial dose should be 2.0 mg.

CLONIDINE INTOXICATION

Conflicting evidence exists concerning use of naloxone for clonidine intoxication, and it is not routinely recommended.

Section Outline:

• ALTERED MENTAL STATUS OF UNDETERMINED ETIOLOGY
  • Naloxone
  • Nalmefene
• RESPIRATORY DEPRESSION FROM KNOWN OPIOID OVERDOSE
• CNS DEPRESSION FROM KNOWN OPIOID OVERDOSE WITHOUT RESPIRATORY DEPRESSION
• REVERSAL OF OPIOID ANESTHESIA
• CLONIDINE INTOXICATION

• Because of the short duration of action for naloxone, opioid toxicity may recur after discharge of the patient.
• Precipitation of withdrawal in opioid-dependent patients may be severe, although not considered life-threatening; however, an agitated patient may disrupt or injure health-care personnel.
• Infants of dependent mothers may develop status epilepticus after naloxone administration.
• Withdrawal seizures in infants may be life-threatening.
• Withdrawal also may be life-threatening in geriatric patients with underlying cardiac diseases.
• Geriatric patients with chronic pain may be opioid dependent.

Poisoning by central nervous system stimulants: opiate antagonists.

See Also: SECTION IV, Clonidine and Narcotics chapters.

RECOMMENDED READING

Gal TJ, Difazio CA. Prolonged antagonism of opioid action with intravenous nalmefene in man. Anesthesiology 1986;64:175-180.

Weisman RS. Naloxone. In: Goldfrank L, Flomenbaum N, Lewin N, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. East Norwalk, CT: Appleton & Lange, 1998.

Author: Kennon Heard

Reviewer: Katherine M. Hurlbut