Buprenorphine/Naloxone Toxicity Treatment & Management

Updated: Dec 29, 2015
  • Author: Timothy J Wiegand, MD; Chief Editor: Asim Tarabar, MD  more...
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Treatment

Prehospital Care

Stabilize all acute life-threatening conditions.

  • Ensure a patent airway. Intubate, if necessary, such as to manage respiratory depression.
  • Establish intravenous (IV) lines.
  • Obtain information about the overdose or exposure, including the following:
    • Amount of pills
    • Dosage
    • Last date the prescription was filled (the bottles should be brought to the hospital if possible)
    • Check blood glucose levels with a fingerstick, or administer a bolus of dextrose if bedside testing is not available.
    • Administration of high-dose naloxone may be indicated if the patient has altered mental status (stupor or coma) and/or depressed respiration.

Naloxone may have variable efficacy in reversing the clinical effects of the Suboxone preparation when administered after an ingestion or overdose. Naloxone has been reported to prevent the clinical effects of buprenorphine if administered prior to buprenorphine; however, it has been reported to be less effective at reversing clinical effects (eg, sedation, respiratory depression) once they are manifest. Despite these data, naloxone has demonstrated efficacy in the treatment of respiratory depression and sedation in pediatric patients inadvertently exposed to Suboxone . [11, 9, 10]

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Emergency Department Care

The clinical presentation of a patient with Suboxone exposure may differ significantly depending on patient characteristics (eg, opioid naive or vulnerable patient, opioid tolerant, or opioid dependent), route of administration, and coingestants. Pediatric patients, in particular infants or toddlers, may experience profound sedation or respiratory depression after Suboxone exposure despite the purported ceiling effect in regard to respiratory depression. Opioid-dependent patients may present to the ED with a precipitated withdrawal syndrome after exposure to Suboxone.

Treatment

See the list below:

  • Treatment of patients with Suboxone (buprenorphine/naloxone) exposure includes mainly supportive therapies such as management of the airway, breathing, and circulation (ABCs). Oxygenation, administration of intravenous fluids, and monitoring may be necessary. Despite the purported safety of the Suboxone formulation compared to full opioid analgesics, coma and significant respiratory depression can occur. Resuscitative maneuvers (eg, intubation) should be performed as needed. After initial stabilization and consideration for administration of naloxone, the patient may need prolonged observation and monitoring.
  • The initially asymptomatic adult patient should be monitored for at least 6 hours after exposure (although pediatric patients may require longer monitoring if there is any question of exposure, as subtle signs and symptoms from Suboxone exposure may be easily missed in this population). If no sedation, respiratory depression, or other signs or symptoms are observed, the patient should be safe for discharge or psychiatric evaluation.

Treatment with naloxone

See the list below:

  • Based on previous clinical experience with adult exposures, it is recognized that relatively low doses of naloxone (eg, 0.4-2 mg), in most instances, will have no effect on reversal of buprenorphine-induced respiratory depression.
  • Relatively high doses (2.5-10 mg) of naloxone caused only partial reversal of the respiratory effects of buprenorphine.
  • Individuals may need multiple repeat doses of naloxone after Suboxone exposure because the half-life for naloxone is significantly less than that observed for buprenorphine (half-life of naloxone in healthy adult patients is 33 min). [6] Most sources provide a range for the duration of naloxone effect from 60 minutes to 4 hours, [10] and the clinical effects seen with buprenorphine may persist for extended durations because of slow dissociation from opioid receptors. Recrudescence of symptoms after initial naloxone administration has been reported. [11]
  • After naloxone administration, pediatric patients, in particular, should be observed either overnight or for at least 8 hours while being monitored for any return of symptoms. Some authors advocate monitoring even asymptomatic pediatric patients for 24 hours due to concern for delayed respiratory depression; [11] however, it appears that patients who are truly asymptomatic, not requiring initial naloxone antidotal therapy or other supportive cares, do not have spontaneous delayed toxicity. Careful initial assessment is important to discern subtle clinical effects.
  • Providers need to consider that there exists a high-degree of stimulation in the emergency department or in the hospital setting that may not exist outside this environment, which may artificially facilitate "alertness". Once this degree of stimulation has diminished, the patient may then become susceptible to the respiratory and CNS depressant effects of the buprenorphine preparation.
  • Some literature reports resistance or difficulty reversing clinical effects of buprenorphine with naloxone. However, clinical trial simulations have demonstrated that complete reversal of respiratory depression by naloxone is feasible. Specifically, complete reversal of low-dose buprenorphine-induced respiratory depression may be achieved with a continuous infusion of naloxone at doses of naloxone from 2-4 mg/70 kg/hour. [6] Additional experiments with incremental doses of buprenorphine and naloxone describe an optimal reversal of respiratory depression with doses of naloxone that would fit a bell-shaped curve with both low- and high-dose naloxone being less effective. The optimal dose for a 0.2 and 0.4 mg exposure of buprenorphine is reported to be from 2-4 mg/70 kg by weight. [20]
  • If administered in single-dose increments, high doses of naloxone (up to 10 mg) may be needed to reverse the clinical effects of buprenorphine.
  • If naloxone does not reverse clinical effects, it is imperative that supportive ventilatory care continues.

Case reports

See the list below:

  • In one report, a 2-year-old boy was found with one tablet of Suboxone (8 mg buprenorphine/2 mg naloxone) in his mouth. The tablet was described as "partly dissolved". The child experienced sedation (but was arousable), nausea, and vomiting. The child was not administered naloxone. The patient was ambulatory at 5 hours postingestion and discharged to home 6 1/2 hours post exposure asymptomatic and stable. [10]
  • In a report of 5 children exposed to Suboxone , the exposure produced a classic opioid toxidrome of respiratory depression (including apnea), CNS depression, and miosis. Four out of 5 children received naloxone, including multiple doses and prolonged, continuous, intravenous infusions, which successfully reversed the respiratory and CNS depression. One child was intubated and mechanically ventilated. The authors of this report caution about the potential for delayed onset of CNS and respiratory depression after buprenorphine exposure. [11]
  • In another case, a 28-month-old boy was found with a Suboxone (8 mg buprenorphine/2 mg naloxone) tablet in his mouth. The tablet was noted to be moist but intact. At 1.5 hours from time of discovery, the child was found with depressed level of consciousness and bradypnea (slow and shallow breathing). CNS and respiratory depression were significantly reversed with 0.2 mg of naloxone administered intramuscularly; however, the child needed 2 additional doses of naloxone, administered intramuscularly (both 0.2 mg) due to persistence of symptoms. The child was discharged, asymptomatic, after being monitored in the PICU overnight (approximately 24 hours). [19]

Decontamination

See the list below:

  • GI decontamination has no role after isolated sublingual Suboxone exposure. The risks of administration of activated charcoal to the patient with altered mental status far outweigh any possible benefit of administration.
  • Patients with protected airway (eg, endotracheal intubation, normal mental status), who were recently exposed to toxic co-ingestants, may receive charcoal after thorough clinical consideration of risks and benefits.
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Consultations

Consult a regional poison control center certified by the American Association of Poison Control Centers (AAPCC) at (800) 222-1222, a medical toxicologist certified by the American College of Medical Toxicology or a clinical toxicologist certified by the American Board of Applied Toxicology.

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