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Buprenorphine use in the Emergency Department Tool

BUPE Overview
Buprenorphine is a synthetic opioid, mu receptor partial agonist, effective in the treatment of acute opioid withdrawal, opioid use disorder (OUD), opioid dependence, and pain.
Buprenorphine has a longer half-life and causes less respiratory depression compared to most other opioids.
In patients with opioid dependence, buprenorphine is very unlikely to cause significant respiratory depression, unless it is combined with another sedative.1
MAT, “Medication for Addiction Treatment” (previously an abbreviation for “medication assisted treatment”) is treatment for opioid addiction, a potentially life-saving intervention, and NOT the “substitution of one addiction for another.”1,2,3,4,5
Section IconBegin Prescribing (B)
Indications and Contraindications
Indications
  • Patients in at least mild acute opioid withdrawal (as defined by Clinical Opiate Withdrawal Score (COWS) score of at least 8).6,7
  • Patients with “Opioid Use Disorder,” OUD, (i.e. addiction), as defined by the DSM V ready to begin medication for treatment.8
    • A patient with OUD who has not used in a day or more, may have a low, or improving COWS (improving acute physiologic withdrawal symptoms), but may benefit from buprenorphine if strong cravings for opioids persist.
Contraindications
  • Patient refusal.
  • Patients taking opioids regularly, who are NOT in opioid withdrawal, or are only in early (less than mild) withdrawal – buprenorphine may precipitate a rapid onset severe withdrawal. For more information see below ↓
    • Consider a prescription for delayed induction (if licensed to prescribe), or advise patient to return later when in withdrawal:6
    • Perform a COWS to determine severity of withdrawal.
  • Patients taking long-acting opioids, particularly methadone. Suggest ensuring patient is in at least moderate withdrawal (COWS at least 13).
    • Additionally, if patient is in methadone MAT program, CAUTION if patient will be resuming dosing in methadone clinic (complex decision).
  • Although less problematic if only treating acute opioid withdrawal, careful considerations should be taken in patients with the following conditions:
    • Alcohol Use Disorder;
    • Other polysubstance abuse history;
    • Taking other sedating medications (e.g. benzodiazepines, “Z-drug” hypnotics for insomnia, carisoprodol “Soma,” pregabalin “Lyrica,” sedating antipsychotics such as quetiapine “Seroquel,” etc.) - [Caution, and dose adjustment advised. See recent FDA comments8,9,10];
  • Moderate to Severe liver disease (OK for single dose for withdrawal). If prescribing, get LFTS, adjust dosing.
  • Pregnancy (point of caution – must be sure patient has OUD and is in withdrawal).
    • Buprenorphine is safe during pregnancy and breast feeding.
  • Increasing evidence that buprenorphine/naloxone dual product formulations are also safe in pregnancy.13,14,15
    • However, opioid withdrawal, including BPW, can increase risk of miscarriage and/or preterm labor.
    • Know local protocols. If greater than 24 weeks gestation, buprenorphine commonly begun with fetal monitoring and close observation (often on the Labor & Delivery unit).
  • Do not delay buprenorphine if patient is in severe opioid withdrawal.
Additional information:
Additional Information on BPW
Precipitated withdrawal can occur when an antagonist (or partial antagonist, such as buprenorphine) is administered to a patient dependent on full agonist opioids. Due to buprenorphine’s high affinity but intermediate intrinsic activity at the mu receptor, the partial antagonist displaces agonist opioids from the mu receptors, without activating the receptor to an equivalent degree, resulting in a net decrease in agonist effect, thus precipitating a withdrawal syndrome.6
It is a common misconception that the naloxone in buprenorphine/naloxone combinations formulations (e.g. “Suboxone,” “Zubzolv,” or “Bunavail) precipitate withdrawal. This is false. The naloxone only precipitates withdrawal if injected into a person dependent upon opioids. Taken sublingually the naloxone has virtually no effect.6
How to avoid precipitated withdrawal:
  • The best way to avoid this condition is through patient education. The patient should be informed, prior to the induction, of what precipitated withdrawal is and how to avoid it. The patient who understands that under reporting his/her use history and last use puts him/her at high risk for rapid and intense onset of withdrawal syndrome, is more likely to accurately report recent/last use.6
  • Discuss with the patient his/her history of withdrawal symptoms. Look for these S/S before administering the first dose at induction.6
  • Perform a COWS score.7
Procedure and Administration
Sublingual (SL) administration is most common, and usually effective (even in severe acute withdrawal). Should not be swallowed; sublingual bioavailability is ~ 50% (buccal and oral much less).8,10,11,12
IV access/IV fluids are usually NOT necessary:
  • Unless acute opioid withdrawal is associated with severe dehydration, or exacerbates other chronic health conditions such as IDDM (DKA), epilepsy (seizures), heart failure, etc.12,18,19
  • Most cases of N/V due to opioid withdrawal can be managed with oral antiemetics until the buprenorphine takes effect (Consider ondansetron ODT followed by buprenorphine SL).18
IV buprenorphine formulation (if available), “Buprenex” is effective, and indicated in cases of severe emesis (when patient can’t absorb sublingual medication). IV buprenorphine not usually necessary, except in cases of severe dehydration or severe illness (when IV access is required).12 The usual beginning dose is 0.3mg IV, effective in 2-5 minutes, peak effect in ~ 15 minutes.
Buprenorphine and Naloxone: mono drug, combination drug, and brand namess. See below for more information ↓
Buprenorphine and Naloxone: mono drug, combination drug, and brand names
Buprenorphine comes in both a mono-product (e.g. brand name of “Subutex”) and as a dual product of ~4mg:1mg ratio of buprenorphine and naloxone (e.g. “Suboxone” and “Zubsolv”), and ~6-7mg:1mg ratios (e.g. “Bunavail”):
  • The absorption of naloxone sublingually is neglibible.16 When absorbed in the stomach naloxone undergoes rapid first pass hepatic metabolism, and thus exerts no clinically significant effect.17
  • Dual product: designed for outpatient prescription addiction treatment to prevent the patient from crushing the tablets, then snorting or injecting (as may be abused with the mono-product).8
  • Some dual products also come in dissolvable film strips (Suboxone and Bunavail)
  • Mono-product: for pregnant women (naloxone may possibly be teratogenic – a pregnancy compliance risk/benefit decision), and when the medication is administered by a nurse (in the ED, in the hospital, etc.).8,11,13,14,15
  • Note: Mono-product formulations are less expensive (but easier to abuse).8

Buprenorphine Quick Product Guide

Sublingual Tablets and Film Strips
  • Most common
  • Dissolve Fast
  • Tend not to taste too bitter
  • ½ life as an analgesic is ~8 hrs
  • ½ life when treating OUD is ~36 hrs (but dose dependent)
Injectable
  • Buprenex – 0.3 mg/1 mg vials
  • Rapid onset, similar half-life to SL bupe formulationst
  • IV buprenorphine not commonly used in the US (check hospital formulary)
Transdermal Patches
  • Butrans FDA indication only for chronic pain in “opioid-experienced” patients
  • Dosing strength of 5, 7.5, 10, 15 and 20 mcg/hr and changed every 7 days
  • 10 mcg/hr patch is ~equianalgesic to 80 mcg/day of oral morphine
Implantable
  • “Probuphine” delivers continuous, stable blood level of buprenorphine for treatment of OUD
  • 4 implants inserted subdermally in upper arm release total dose of buprenorphine similar to a daily sublingual 8 mg dose for 6 mo.
Depot Subcutaneous
  • “Sublocade”
  • Injected monthly in 100 and 300 mg doses into abdominal subcutaneous tissue
  • Continuously releases dosage equivalent to 8-24 mg/day of sublingual buprenorphine
  • Other products soon to be released.
Dosing for Acute Withdrawal or Initiating MAT
Most patients coming to the ED in opioid withdrawal are likely to be moderate to heavy users (using ~> 1 gram/day of heroin, or ~>80mg/day of oxycodone or hydrocodone): Initiate treatment with buprenorphine 8mg SL.6,8,12,18,19
For patients using < 0.5 G/day of heroin, or <40mg/day of oxycodone/hydrocodone, may initiate treatment with buprenorphine 2-4mg SL.16,8,12,18,19 For more information, see below ↓
Many patients have previously experienced acute opioid withdrawal and have self-medicated with buprenorphine. Consider asking the patient about the dose the patient has tolerated or needed in the past.
Although sublingual buprenorphine peaks at ~ 60 minutes, improvement is usually noticeable in ~15-20 minutes. If not improving after 30 minutes, consider repeating the dose.8,18,19
Majority of ED patients in acute opioid withdrawal will be adequately controlled with 8mg to 16mg (but some patients may need more).
  • If possible, the goal should be to abolish withdrawal symptoms while the patient is in the ED, so that the patient will be more receptive to peer counseling, and referral to outpatient treatment.
  • Traditional guidelines advise a limit of 8mg on the first day of office induction. However, many patients have previously tolerated much higher doses of buprenorphine (self-treatment, or prior treatment). Furthermore, with adequate observation in the ED, a patient’s initial dose can be titrated up until acute withdrawal symptoms have resolved.8,18,19,20
    • In some ED protocols, if there are no contraindications, a total of up to 32mg is administered, “buprenorphine loading,” (with 60 minutes of post dose observation), to extend the time window for patients to follow up in a clinic before withdrawal symptoms return.8,18,19,20 For more information, see below ↓
    • If treated at a lower dose in the ED (e.g. 8mg SL, as per some protocols), a patient may need to return the next day for additional dosing (see “3 Day Rule” discussion), and may benefit from a higher dose on the 2nd day (e.g. 16mg SL).6,8
    • If the ED physician has an “X-waiver,” a prescription can be provided, in lieu of “buprenorphine loading,” or a planned return ED visit.6,8
    • Patients are dosed as MAT, from 2 to 32mg/SL per day (daily or divided BID), and the majority of patients will ultimately be treated with doses of 12 to 24mg/day (daily or divided BID)
Heroin street terminology, and gram equivalents
Although heroin potency/concentration is inconsistent, and may vary widely, as a general rule, using a gram/day of black tar heroin (the most prevalent in the USA), is moderate use. “China white” heroin is usually less concentrated.
Some heroin users are able to clearly speak in terms of “grams,” but others may only speak in terms of “20’s,” “BB’s,” “8 Balls,” “bags,” “balloons,” etc., but they know if they are low or high dose users. May help to inquire how often the patient doses (3x or more/day?).
Buprenorphine Loading Dose Precautions
Although less problematic if only treating acute opioid withdrawal, careful considerations should be taken in patients with the following conditions:
  • Alcohol Use Disorder;
  • Other polysubstance abuse history;
  • Taking other sedating medications (e.g. benzodiazepines, “Z-drug” hypnotics for insomnia, carisoprodol “Soma,” pregabalin “Lyrica,” sedating antipsychotics such as quetiapine “Seroquel,” etc.) -- [Caution, and dose adjustment advised. See recent FDA comments8,9,10];
Moderate to Severe liver disease (OK for single dose for withdrawal). If prescribing, get LFTS, adjust dosing
Buprenorphine Precipitated Withdrawal (BPW) Management
If buprenorphine precipitates acute opioid withdrawal, there are two avenues of treatment, which can be administered exclusively or in combination.
  • Traditional non-opioid agonist, symptom focused medications (alpha-2 agonists, anti-emetics, anti-diarrhea medications, anxiolytics, etc.) .Some institutional protocols for BPW only use non-opioid agonists. Watch for sedation (a common complication of these medications). A prolonged ED stay may be required. View table of medications below ↓
  • Additional buprenorphine: Although there is limited published data, it is the experience among many experts, that generally, additional buprenorphine is more rapidly effective, and less sedating (and potentially obviates the need for an IV). Depending on initial dose of buprenorphine administered, administer additional 4-8mg Q 30 min until withdrawal symptoms abate.19,20,21,22
  • Observe for at least 30 minutes after last dose of buprenorphine (when treating BPW) for sedation or adverse effects. In doses above 16mg SL patients, should be observed for one hour.8,19,20,22
Nausea & Vomiting after buprenorphine – special note
Buprenorphine does make some patients nauseated (as all opioids can), even patients with OUD, and this nausea can be severe.
  • If the patient starts vomiting after buprenorphine administration, evaluate for other signs of withdrawal (perform a COWS):
  • If COWS is low, then nausea is probably not due to precipitated withdrawal. Treat with anti-emetics.
  • If COWS is at least 8, or higher than the initial COWS, then consider additional buprenorphine (and anti- emetics), as treatment for BPW (section above).
Other Appropriate Withdrawal Management Medications
Scroll Chart →

Specific Symptom Management Medications

Symptoms
Drug
Dosing
Links
Nausea and Vomiting
Promethazine (Phenergan)
25 mg orally 6 hr as needed for nausea (can also be effective for restless leg syndrome
 
Ondansetron (Zofran)
4-8 mg PO (by mouth) every 8 hr as needed
Diarrhea
Loperamide (Imodium)
4 mg orally for diarrhea, then 2 mg orally every 6 hr as needed for loose bowel movements (Max. dose = 16 mg/24 hr)
Myalgias
Acetaminophen (Tylenol)
325-650 mg orally every 8 hr with meals then reduce to twice daily as needed
 
Ibuprofen (Advil)
400-800 mg orally every 8 hr with meals then reduce to twice daily as needed
Anxiety, dysphoria, lacrimation, rhinorrhea
Hydroxyzine (Vistaril)
25-50 mg orally three time daily as needed
 
Diphenhydramine (Benadryl)
25-50 mg orally every 6 hr as needed
Insomnia
Trazodone (Trazorel)
50-100 mg orally at bedtime as needed
 
Quetiapine (Seroquel) Melatonin
50-100 mg orally at bedtime as needed
5-10 mg orally at bedtime as needed
Abdominal Cramping
Dicylcomine (Bentyl)
20 mg every 6 hr as needed for abdominal cramping
Restlessness
Clonidine (Catapres) Also effective for stress-induced cravings in the long term
0.1-0.2 mg TID (3 times daily) for 3 days, then 0.1 mg BID (2 times daily) (often used for blood pressure)
 
Gabapentin (Neurontin) Also used for neuropathic pain
300-600 mg TID
Other Medications
Ketamine
Myalgias, Agitation, Restlessness
0.1-0.3 mg/kg slow IVP or IVPB Q 30 min (watch for hallucinations)
Lofexidine
Mitigation of opioid withdrawal symptoms
3x0.18 mg tablets (orally) 4 times every 6 hr as needed. May be continued for up to 14 days with dosing guided by symptoms. Discontinue with a gradual dose reduction over 2-4 days.
Section IconUtilize Naloxone (U)
Naloxone in the ED
Naloxone distribution programs and community overdose education and naloxone distribution programs have been shown to decrease overdose deaths, and not increase opioid use. The emergency department (ED) is an ideal setting for opioid overdose death prevention through the distribution of (or prescribing of) overdose naloxone rescue kits, overdose prevention and response education.
  • In multiple states and municipalities, naloxone can be obtained without a prescription, and in others there are also good Samaritan laws to protect those who administer it. Learn More
Forms of Naloxone for Patients/Community Use
For more information and product comparison of Naloxone Download PDF
Section IconProvide Linkage to Treatment (P)
Opportunity for Intervention
Buprenorphine often produces a rapid, dramatic improvement in opioid withdrawal symptoms.
After receiving treatment for acute opioid withdrawal, patients may be more receptive to discussing addiction treatment, and referral to a treatment center.5 Engage social services and/or a peer counselor to facilitate when available.5
Key Points
If the ED physician only has a phone number or website to offer for referral, it is still preferable to treat withdrawal with buprenorphine than a traditional “kick kit.”
If buprenorphine is used for acute withdrawal management in the ED the patient can still be treated with buprenorphine, methadone, or potentially naltrexone, when receiving follow up care for OUD treatment in an addiction clinic.19
MAT is usually only successful as a long-term treatment. When buprenorphine or other MAT medications are used just to “detox” patients, there is an extremely high rate of relapse. Best to set this expectation with the patient.
Discharge Instructions
If there is a clinic which provides MAT to refer patients for treatment, be sure to refer!
  • Ideally an ED case manager can optimize successful clinic referral with awareness of clinic hours, breadth of clinic services, insurance acceptance, etc.
Remind the patient that buprenorphine is an opioid, and
  • Must NOT be mixed with alcohol, benzos, etc., as it can be extremely dangerous
  • Must be stored safely and securely in a locked/child-proof container and kept away from the reach of children
Section IconEducate on Rules & Regulations (E)
X-waiver
An X-waiver to your DEA registration is NOT required to order/administer a dose of buprenorphine in the hospital, or in the ED.23
A patient may come to the ED 3 days consecutively to be treated with buprenorphine in the ED, for opioid withdrawal or for the initiation of MAT (“the 3 day rule”).18
An X-waiver IS, however, required in order to WRITE A PRESCRIPTON (to be filled at a pharmacy) for buprenorphine for addiction treatment, withdrawal, or to “detox.”23
Most hospitals are probably NOT licensed to dispense buprenorphine (patients should NOT be sent home with take home doses of buprenorphine, unless the ED provider has an X-waiver, and approved by the hospital).23
Any practitioner with a DEA registration can prescribe buprenorphine for pain management.23
Caution:
Buprenorphine is a potent analgesic, and should be considered as a pain management option, particularly for patients already taking buprenorphine.
However, dosing for acute pain, in the opioid naïve is not yet well determined, but is markedly lower than dosing to treat OUD, and even at low doses, in the opioid naïve can result in prolonged sedation and/or nausea.
If treating acute pain with buprenorphine, be sure that the indication for pain is clearly noted in the chart.
“Butrans” dermal patches, have only been FDA approved for pain management in opioid experienced/tolerant patients.
References
  1. Fullerton CA, et al. Medication-assisted treatment with methadone: assessing the evidence. Psychiatric services in advance. November 18, 2013
  2. Thomas CP, et al. Medication-assisted treatment with buprenorphine: assessing the evidence. Psychiatric services in advance. November 18, 2013
  3. Sordo L, Barrio G, Bravo M, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies BMJ 2017; 357:j155
  4. Surgeon General’s Report on Alcohol, Drugs, and Health. Learn More
  5. Ma J, Bao YP, Wang0 et al. Effects of medication-assisted treatment on mortality among opioids users: a systematic review and meta-analysis. Mol Psychiatry. 2018 Jun 22. doi: 10.1038/s41380-018-0094-5
  6. D'Onofrio G, O'Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015 Apr 28;313(16):1636-440
  7. Wesson, D. R., & Ling, W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs, 35(2), 253–9.
  8. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, Md: Substance Abuse and Mental Health Services Administration, 2004
  9. FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. Download PDF
  10. Welsh, C and Valadez-Meltzer, A. Buprenorphine, A (Relatively) New Treatment for Opioid Dependence. Psychiatry, 2005 Dec; 2(12): 29–39.
  11. Kuhlman JJ, Lalani S, Magluilo J, et al. Human pharmacokinetics of intravenous, sublingual, and buccal buprenorphine. J Anal Toxicol. 1996 Oct;20(6):369-78.
  12. Berg, M. L., et al. "Evaluation of the use of buprenorphine for opioid withdrawal in an emergency department." Drug & Alcohol Dependence 86.2 (2007): 239-244.
  13. Nguyen L, Lander LR, O'Grady, KE, et al. Treating women with opioid use disorder during pregnancy in Appalachia: Initial neonatal outcomes following buprenorphine + naloxone exposure. Am J Addict. 2018 Mar;27(2):92-96. doi: 10.1111/ajad.12687. Epub 2018 Feb 23.
  14. Debelak K, Morrone WR, O'Grady KE. Buprenorphine + naloxone in the treatment of opioid dependence during pregnancy-initial patient care and outcome data. Am J Addict. 2013 May-Jun;22(3):252-4
  15. Wiegand SL, Stringer EM, Stuebe AM, et al. Buprenorphine and naloxone compared with methadone treatment in pregnancy. Obstet Gynecol. 2015 Feb;125(2):363-8.
  16. Harris DS, Mendelson JE, Lin ET, et al. Pharmacokinetics and subjective effects of sublingual buprenorphine, alone or in combination with naloxone: lack of dose proportionality. Clin Pharmacokinet. 2004;43(5):329-40
  17. Smith K, Hopp M, Mundin G, et al. Low absolute bioavailability of oral naloxone in healthy subjects. Int J Clin Pharmacol Ther. 2012 May;50(5):360-7.
  18. Oreskovich MR, Saxon AJ, Ellis ML, et al. A double-blind, double-dummy, randomized, prospective pilot study of the partial mu opiate agonist, buprenorphine, for acute detoxification from heroin. Drug Alcohol Depend. 2005 Jan 7;77(1):71-9.
  19. Expert Opinion.
  20. Ang-Lee K, Oreskovich MR, Saxon AJ, et al. Single dose of 24 milligrams of buprenorphine for heroin detoxification: an open-label study of five inpatients. J Psychoactive Drugs. 2006 Dec;38(4):505-12.
  21. Jain K, Jain R, Dhawan A. A double-blind, double-dummy, randomized controlled study of memantine versus buprenorphine in naloxone-precipitated acute withdrawal in heroin addicts. J Opioid Manag. 2011 Jan- Feb;7(1):11-20.
  22. Jutras-Aswad D, Widlitz M, Scimeca MM. Treatment of buprenorphine precipitated withdrawal: a case report. Am J Addict. 2012 Sep-Oct;21(5):492-3.
  23. Special Circumstances for Providing Buprenorphine Learn More
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Acknowledgments

A collaborative educational project of the American College of Emergency Physicians and the American Society of Addiction Medicine.

CONTRIBUTORS

Authors:
Eric Ketcham, MD, MBA, FACEP, FASAM, FACHE Shawn Ryan, MD, MBA, ABEM, ABAM

Reviewers:
Andrew Herring, MD Christie DeFranco, DO Evan Schwarz, MD Herbie Duber, MD, MPH, FACEP Kate Hawk, MD Kurt Kleinschmidt, MD

 

ACEP Staff
Sam Shahid, MBBS, MPH Margaret Montgomery, RN, MSN Lori Vega Riane Gay, MPA

 

Support made possible by Indivior

 

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