Naloxone

Administration of naloxone causes the release of catecholamines, which may precipitate acute withdrawal or unmask pain in those who regularly take opioids. Symptoms of acute withdrawal in opioid-dependent patients may include pain, tachycardia, hypertension, fever, sweating, abdominal cramps, diarrhea, nausea, vomiting, agitation, and irritability. In neonates born to mothers with opioid dependence, opioid withdrawal may be life-threatening and symptoms may include excessive crying, shrill cry, failure to feed, seizures, and hyperactive reflexes. In settings other than acute opioid overdose (eg, postoperative patients), carefully titrate the dose to reverse hypoventilation; do not fully awaken patient or reverse analgesic effect. The 2 mg nasal dose (off-label) is less likely to precipitate severe opioid withdrawal compared to the 4 mg dose; however, the 2 mg dose may not provide an adequate and timely reversal in patients who have been exposed to an overdose of a potent or very high dose of opioids. Disease-related concerns:

Use with caution in patients with cardiovascular disease or in patients receiving medications with potential adverse cardiovascular effects (eg, hypotension, pulmonary edema or arrhythmias); pulmonary edema and cardiovascular instability, including ventricular fibrillation, have been reported in association with abrupt reversal when using opioid antagonists.

Use caution in patients with history of seizures; avoid use in the treatment of meperidine-induced seizures. Dosage form specific issues:

When administered to infants Other warnings/precautions:

To prevent overdose deaths, there are initiatives to dispense naloxone for self- or buddy-administration to patients at risk of opioid overdose (eg, recipients of high-dose opioids, suspected or confirmed history of illicit opioid use) and individuals likely to be present in an overdose situation (eg, family members of illicit drug users) (Albert 2011; Bennett 2011). Clinical practice guidelines recommend patients being treated for opioid use disorder should be given prescriptions for naloxone. Patients and family members/significant others should be trained in the use of naloxone in overdose (Kampman [ASAM 2015]). Evzio is indicated for emergency treatment. Needleless administration via nebulization and the intranasal route using the injectable solution (with a mucosal atomization device) by first responders and bystanders has also been described (Doe-Simkins 2009; Weber 2012). Needleless administration provides an alternative route of administration in patients with venous scarring due to illicit drug use (eg, heroin). There is a low incidence of death following naloxone reversal of opioid toxicity in patients who refuse transport to a healthcare facility (Wampler 2011). Nevertheless, patients who received naloxone in the out-of-hospital setting should seek immediate emergency medical assistance after the first dose due to the likelihood that respiratory and/or central nervous system depression will return.

Recurrence of respiratory and/or CNS depression is possible if the opioid involved is long-acting; continuously observe patients until there is no further risk of recurrent respiratory or CNS depression.

Reversal of partial opioid agonists or mixed opioid agonist/antagonists (eg, buprenorphine, pentazocine) may be incomplete and larger or repeat doses of naloxone may be required.

Appropriate use: Excessive dosages should be avoided after use of opioids in surgery. Abrupt postoperative reversal may result in nausea, vomiting, sweating, tachycardia, hypertension, seizures, and other cardiovascular events (including pulmonary edema and arrhythmias).