Naloxone Indications Beyond Opioid Overdose
Naloxone has three FDA-approved indications beyond acute opioid overdose: (1) reversal of opioid-induced respiratory depression in therapeutic settings, (2) diagnosis of suspected acute opioid overdosage, and (3) as an adjunctive agent to increase blood pressure in septic shock. 1
Primary Non-Overdose Indications
Reversal of Therapeutic Opioid-Induced Respiratory Depression
Naloxone is indicated for complete or partial reversal of opioid depression, including respiratory depression, induced by therapeutic use of natural and synthetic opioids including propoxyphene, methadone, and mixed agonist-antagonist analgesics (nalbuphine, pentazocine, butorphanol, cyclazocine). 1
In cancer patients receiving opioid therapy, naloxone should be administered cautiously when respiratory depression develops, as it may precipitate acute withdrawal syndrome in opioid-tolerant patients. 2
For opioid-induced respiratory depression in therapeutic settings, use low-dose naloxone (0.04-0.4 mg) with careful titration to avoid precipitating severe withdrawal, hypertension, tachycardia, pulmonary edema, cardiac arrhythmias, and seizures. 2, 3
Diagnostic Use
- Naloxone is FDA-approved for diagnosis of suspected or known acute opioid overdosage, serving as a diagnostic tool when opioid intoxication is uncertain. 1
Adjunctive Use in Septic Shock
Naloxone may be useful as an adjunctive agent to increase blood pressure in the management of septic shock. 1
Naloxone has been shown in some cases of septic shock to produce a rise in blood pressure lasting up to several hours, though this pressor response has not been demonstrated to improve patient survival. 1
Treatment with naloxone in septic shock has been associated with adverse effects including agitation, nausea and vomiting, pulmonary edema, hypotension, cardiac arrhythmias, and seizures. 1
The decision to use naloxone in septic shock should be exercised with caution, particularly in patients who may have underlying pain or have previously received opioid therapy and may have developed opioid tolerance. 1
Optimal dosage and treatment regimens for septic shock have not been established due to limited patient numbers. 1
Preventive Co-Prescribing for High-Risk Patients
Risk Mitigation Strategy
Clinicians should consider offering naloxone when prescribing opioids to patients at increased risk for overdose, including patients with history of overdose, history of substance use disorder, those taking benzodiazepines with opioids, patients at risk for returning to high doses after tolerance loss (e.g., recently released from prison), and patients taking higher dosages of opioids (≥50 MME/day). 2
Naloxone co-prescribing is a risk mitigation strategy for patients on chronic opioid therapy, not treatment of active overdose. 2
Practices should provide education on overdose prevention and naloxone use to patients receiving naloxone prescriptions and to members of their households. 2
Results from a nonrandomized intervention study showed that patients receiving long-term opioid analgesia who were coprescribed naloxone had fewer opioid-related emergency department visits compared with those who were not prescribed naloxone. 2
Availability for Caregivers
Naloxone may be made available to caregivers to administer when needed for patients taking opioids who are at high risk for respiratory depression and sedation. 2
The availability of needle-free naloxone preparations (e.g., nasal spray) facilitates use in the outpatient setting. 2
Caregivers who are provided naloxone must be educated in the proper indications and usage to prevent inappropriate administration. 2
Critical Safety Considerations
Avoiding Precipitated Withdrawal
In opioid-tolerant patients, abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, pulmonary edema, cardiac arrhythmias, and cardiac arrest. 2
Naloxone should be administered cautiously in opioid-tolerant patients to avoid precipitating acute opioid withdrawal syndrome. 2, 4
The severity and duration of withdrawal syndrome are related to the dose of naloxone and to the degree and type of opioid dependence. 1
Duration of Action Concerns
Since the duration of action of naloxone (typically 30-60 minutes, up to 2 hours) may be shorter than that of some opioids, the effects of the opioid may return as the effects of naloxone dissipate. 1, 5
Patients should be observed in a healthcare setting until the risk of recurrent opioid toxicity is low and vital signs have normalized. 2
Repeated small doses or an infusion of naloxone can be beneficial if recurrent opioid toxicity develops. 2
End-of-Life Considerations
- At end-of-life in patients receiving comfort measures only, slowed respiration is expected and naloxone administration may be inconsistent with goals of care in these patients. 2
Common Clinical Pitfalls
A retrospective case series found that no patient receiving long-term opioid therapy who was administered naloxone had evidence of respiratory depression, and all naloxone doses administered were higher than recommended by national guidelines for this patient group. 6
Verbal and physical stimulation as well as oxygenation should be considered prior to naloxone administration in patients on chronic opioid therapy, followed by close observation, hydration, renal function tests and opioid dose review. 6
Clinicians often overestimate the dose of naloxone needed to achieve the desired clinical outcome, precipitating acute opioid withdrawal syndrome. 3