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Medications for management of acute opioid withdrawal in adolescents in the emergency setting

Medications for management of acute opioid withdrawal in adolescents in the emergency setting
Medication Initial dose (adolescents) Indication
Opioid
Buprenorphine*

NOTE: Before beginning this regimen, patient needs to have entered withdrawal generally with COWS score >5.

2 mg SL; If withdrawal persists 30 to 60 minutes later without sedation, can give additional 2 to 4 mg SL dose.

Can give additional 2 to 4 mg SL every 1 to 2 hours for continued withdrawal, without increasing COWS score, up to 16 mg total in 24 hours; however, some patients may require up to 24 mg

If COWS score increases, stop induction, treat symptoms with non-opioid adjunctive medications, and reassess in 24 hours.

Parenteral (IV or IM) administration is not routinely used for opioid withdrawal in adolescent patients.
  • Acute opioid withdrawal.Δ
  • A lower-dose initiation is generally preferred in adolescent patients to minimize exposure to opioids (including buprenorphine) during this unique period of brain development and to avoid precipitated withdrawal from potential exposure to fentanyl.
  • Buprenorphine induction is timed to start after the appropriate amount of time following the last opioid exposure has passed. Refer to separate UpToDate table of time windows from last opioid exposure to introducing buprenorphine in adolescents.
  • Buprenorphine is metabolized in the liver by CYP3A4; co-administration with strong inhibitors or inducers of CYP3A4 may require therapy adjustment; refer to drug interactions program.
  • Non-opioid adjunctive medications (below) can be administered with buprenorphine to treat withdrawal symptoms while the buprenorphine dose is gradually titrated.
Non-opioid adjunctive medicationsΔ
Clonidine

0.1 mg orally, may be repeated every 6 to 8 hours if needed with monitoring of blood pressure and heart rate; check blood pressure prior to each dose and hold the dose if hypotension is present

In younger adolescents, start with 0.05 mg initial dose (requires splitting 0.1 mg tablet)

 Anxiety, restlessness, dysphoria, sweating, with elevated or normal blood pressure and heart rate
Ondansetron 4 to 8 mg IV/IM/oral every 4 to 8 hours as needed

Nausea, vomiting

Diphenhydramine and hydroxyzine may also be useful for anxiety and restlessness
Diphenhydramine 1 mg/kg IV, IM or orally every 6 hours as needed; maximum: 50 mg/dose
Hydroxyzine 1 mg/kg IM or orally every 6 hours as needed; maximum: 50 mg/dose
Loperamide 4 mg orally, followed by 2 mg every loose stool; maximum: 8 mg/24 hours Diarrhea, stomach cramps
Bismuth subsalicylate 524 mg orally every 30 to 60 minutes as needed; maximum 4200 mg/24 hours
Acetaminophen 10 to 15 mg/kg orally every 4 to 6 hours as needed; maximum 75 mg/kg/24 hours not to exceed 4000 mg/24 hours Pain, myalgia
Ibuprofen 4 to 10 mg/kg (maximum 600 mg/dose) orally every 6 to 8 hours as needed; maximum 40 mg/kg/24 hours not to exceed 2400 mg/24 hours
The doses listed in this table are appropriate for adolescents aged 12 through 17 years with normal liver function. For additional information on managing symptoms of withdrawal in patients cared for in a non-emergency setting, refer to the UpToDate topics discussing treatment of opioid use disorder.

COWS: Clinical Opiate Withdrawal Scale; IM: intramuscular; IV: intravenous; SL: sublingual.

* Generally administered as a sublingual film or tablet containing buprenorphine 2 mg and naloxone 0.5 mg. The naloxone component has no clinically significant effect when administered sublingually. It is included to deter misuse (eg, IV injection or intranasal use) of buprenorphine. Additional sublingual film strengths include buprenorphine-naloxone 4 mg/1 mg, and 8 mg/2 mg. Sublingual film may be split in half if needed to deliver the appropriate dose.

¶ Buprenorphine is a partial opioid agonist. An increasing COWS score may suggest buprenorphine-precipitated withdrawal.

Δ Opioids are generally more effective than non-opioid adjunctive medications and should be offered to patients in withdrawal. If withdrawal is precipitated by an opioid antagonist (eg, naloxone), non-opioid medications or buprenorphine are reasonable options. Refer to UpToDate topics on opioid withdrawal in adolescents.

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