Frequently Asked Questions

This information is intended for healthcare providers and subject matter experts, it is not intended for use by patients and the general population.

These responses are an educational aid to practice and do not set a standard of care. They do not set a single best course of management, nor do they include all available management options. They were developed by an interdisciplinary team based on published evidence and expert opinion; as the literature develops best practices may change.

They should never be used as a substitute for clinical judgement. Individual providers are responsible for assessing the unique circumstances and needs of each case. Adherence to these guidelines will not ensure successful treatment in every situation. This information is intended for healthcare providers and subject matter experts, it is not intended for use by patients and the general population.

About Buprenorphine

Buprenorphine in the Emergency Department

Medication for Opioid Use Disorder (MOUD) in the Hospital

PHARMACY

Referrals from the Acute Care Setting

Policy

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About Buprenorphine

What is buprenorphine?

Buprenorphine (BUP) is a unique schedule III opioid used for the treatment of acute and chronic pain, opioid withdrawal, and maintenance treatment of opioid addiction. The most common formulations are sublingual (alone or in combination with naloxone: Suboxone), transdermal (10mcg/hr = about 0.5mg/day), and intravenous (Buprenex).

How long has buprenorphine been around?

Since the 1970’s. Initially, buprenorphine was used as an intravenous, perioperative, analgesic. It was used later because of its long-action ability to block the euphoric effects of heroin. Safety profile sublingual buprenorphine was developed for opioid substitution treatment in the 1990s and was approved for use in the US in 2002. Most recently, buprenorphine is increasingly used for the treatment of chronic pain.

Is buprenorphine safe?

Rates of adverse events following home or emergency department initiation of buprenorphine are very low. Because buprenorphine has a “ceiling” effect at usual doses with opioid receptor agonism, it has a very low rate of respiratory depression or overdose. Case reports have occurred, usually when buprenorphine is coadministered with large amounts of alcohol or benzodiazepines. A more common risk is precipitated withdrawal if buprenorphine is given too soon--this is uncomfortable but not life threatening. In published data, reductions in the use of illicit opioid medications were reported, conferring a presumed safety benefit. Additionally, a Cochrane Analysis reported no difference in adverse event rates with buprenorphine compared to non-opioid treatments for managing opioid withdrawal.

  1. Cunningham CO, Giovanniello A, Li X, Kunins HV et al. A Comparison of Buprenorphine Induction Strategies: Patient-Centered Home-Based Inductions versus Standard-of-Care Office-Based Inductions.  J Subst Abuse Treat. 2011 Jun;40(4):349-56.

  2. Lee JD, Vocci F, Fiellin DA. Unobserved "home" induction onto buprenorphine. J Addict Med. 2014 Sep-Oct;8(5):299-308.

  3. Erik W. Gunderson et al., "Unobserved versus Observed Office Buprenorphine/Naloxone Induction: A Pilot Randomized Clinical Trial," Addictive Behaviors 35, no. 5 (May 2010): 537-40, doi:10.1016/j.addbeh.2010.01.001.

  4. D'Onofrio G, O'Connor PG, Pantalon MV, Chawarski MC et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015 Apr 28;313(16):1636-44

  5. D'Onofrio G, Chawarski MC, O'Connor PG, Pantalon MV et al. Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: Outcomes During and After Intervention. J Gen Intern Med. 2017 Jun;32(6) 

How long does buprenorphine take to act and when does it peak?

Sublingual buprenorphine takes 15 minutes to act when held under the tongue and peaks in one  hour. A typical 0.3mg IV buprenorphine begins to work immediately after an IV push with peak effect in 5-10 minutes.

What is the difference between buprenorphine and Suboxone®?

Suboxone is the trademark name for buprenorphine + naloxone. The naloxone component is an abuse deterrent that is inert when the tablet is taken sublingually. The naloxone is only active if the tablet is injected.

Are there contraindications for buprenorphine?

If a patient dependent on opioids takes buprenorphine when they have opioid in their system, the buprenorphine will rapidly block the effects of their opioid causing what is termed “precipitated withdrawal.” The severity of this effect varies from mild discomfort to severe distress. This is why there is a washout period for opioid tolerant patients before starting buprenorphine.

Once significant withdrawal has begun the administration of buprenorphine produces relief of withdrawal, anxiolysis, and analgesia. Some patients with significant liver disease (ALT > 5x normal) may not be able to take buprenorphine long-term. Avoid in patients with hypersensitivity to buprenorphine or naloxone.

Is there a need for an Alpha 2 agonist such as Clonidine?

No, nothing else is needed. However, adjunct medications such as clonidine, zofran, and loperamide can be helpful in some cases. We avoid routine use of benzodiazepines.

How long do people use buprenorphine?

It depends.

An ED patient might receive a few doses buprenorphine to treat withdrawal and then go right back to using street opioids. Most patients with opioid use disorder don’t establish long-term abstinence on the first go around. The hope is that, having a positive experience with buprenorphine treat- ment can be a motivation to pursue long-term treatment.

The evidence is clear: the more weeks of stability on buprenorphine that a person with opioid use disorder can string together, the more their mortality risk goes down. We see patients stop and start frequently and that’s common. Each medical encounter is an opportunity to make another attempt at long-term recovery.

Once patients have stabilized on buprenorphine patients should be contin- ued on it indefinitely. When patients stop their maintenance buprenorphine or methadone, all cause mortality more than doubles. The underlying concept is that the neural architecture of the brain is changed by addiction and it takes years to recover. When patients are in recovery they develop whole new patterns of behavior, stress response, and reward seeking that then get “hardwired” into the brain. This process cannot be rushed and has very little to do with patient motivation or insight.

Sordo L, Barrio G, Bravo M, Indave B, Degenhardt L, Wiessig L, Ferri M, Pastor-Barriuso R. Mortality Risks During and After Opioid Substitution Treatment: Systematic Review and Meta-Analysis of Cohort Studies. BMJ 2017; 357:j1550.

 

Buprenorphine in the Emergency Department

What forms of buprenorphine should we have on the formulary?

At minimum, sublingual tablet formulations of buprenorphine should be available to be administered and/or prescribed from the ED. The most common formulations are sublingual (alone or in combination with naloxone: Suboxone), transdermal (10mcg/hr = about 0.5mg/day), and intravenous (Buprenex).

When do you administer buprenorphine in the ED?

Buprenorphine will displace other drugs from opioid receptors, replacing the high-intensity stimulation from drugs like heroin or oxycodone with stable drug levels over 2-3 days, eliminating craving and withdrawal symptoms. Starting BUP when patients have moderate withdrawal symptoms provides immediate relief, stopping withdrawal discomfort without causing euphoria or sleepiness. Do NOT start BUP on opioid-dependent patients who are not in withdrawal. For these patients, the BUP causes withdrawal, and decreases patients’ desire to stay on BUP or to try BUP again.

How does a clinician give buprenorphine in the ED?

Generally start with  4-8 mg as sublingual tablet (Suboxone or Subutex) under the tongue. IV BUP (0.3mg ) can be used for patients unable to tolerate sublingual tablets. If the tablets are swallowed, very little BUP gets absorbed.  Repeat doses up to 32mg SL can be administered depending on the clinical situation. It is okay to administer BUP in low-acuity, “fast-track” type areas of the ED. A single 8 mg dose will have peak effect by about 1 hour and control withdrawal symptoms 6-12 hours. Transdermal buprenorphine will generally be too weak to prevent withdrawal symptoms and is best used for patients with chronic pain. See ED-BRIDGE Guide to Emergency Buprenorphine Treatment.

How should an ED discharge a patient?

Always offer a naloxone prescription or kit.

  • Option 1. No DEA X waiver: Prescribe comfort meds (e.g. clonidine, loperamide, ondansetron, NSAIDS) and recommend follow-up at treatment center. It is legal in all states to offer return ED visits for BUP administration for 3 days in a row if necessary.

  • Option 2. DEA X waiver: Give bridge script to last until outpatient visit: e.g., 8mg Suboxone, SL tabs; Take 1 tab under the tongue twice a day for withdrawal symptoms; Dispense #6-7

Medication for Opioid Use Disorder (MOUD) in the Hospital

What licensing do I need to prescribe buprenorphine or methadone for an inpatient, either as a new start or as an initiation?

No additional licensing is required to prescribe buprenorphine or methadone for patients in the hospital who are admitted with a primary medical problem other than opioid dependency. This is true even for patients who have not previously started to take buprenorphine or methadone. An X (Data 2000) waiver is required for discharge prescriptions, therefore it is recommended to have at least one provider who is X waivered. See appendix for full regulations.

What if the patient does not have a primary medical problem separate from opioid dependency or is not admitted?

Even in cases where a patient does not have a primary medical problem, buprenorphine or methadone may be administered for up to 72 hours. Most often, this comes up when a patient presents to the ED in withdrawal but does not need admission, or when an admitted patient has been discharged and has a short wait before they can be seen in an outpatient clinic. Buprenorphine or methadone can be administered without registration as a narcotic treatment program under Title 21, Code of Federal Regulations, Part 1306.07(b), provided:

  • Not more than one day’s medication may be administered or given to a patient at one time

  • Treatment may not be carried out for more than 72 hours

  • The 72-hour period cannot be renewed or extended  

This is generally done with the intent to bridge a patient until they can connect with ongoing treatment, often in an ED or bridge clinic setting.  Of note, medications need to be administered i.e. dosed on site, not prescribed.  Patients should not be admitted to the hospital solely for this purpose. After the 72-hours, the patient will need to receive methadone or buprenorphine from a opioid treatment program (OTP). Alternatively, prescribers with a DATA 2000 waiver are able to prescribe buprenorphine for the treatment of opioid use disorder outside on an OTP.

I want to continue methadone for a patient stabilized on an outpatient dose, what steps should I take?

It is recommended to continue a patient’s methadone therapy during their inpatient hospitalization whenever possible. The last dose amount and date should be confirmed with the patient’s opioid treatment program upon admission.

What if I cannot confirm a patient’s outpatient methadone dose?

If a patient has evidence of opioid use disorder, and presents with opioid withdrawal symptoms, but their outpatient methadone clinic cannot be reached to confirm a dose, they should be treated as a new methadone start. Give methadone per the guidelines, and call the methadone clinic as early as possible to confirm date and amount of their last dose.

I want to continue buprenorphine for a patient stabilized on an outpatient dose, what steps should I take?

A call to the patient’s pharmacy can help confirm that a patient is prescribed buprenorphine and at what dose. Additionally, buprenorphine prescriptions are transmitted to CURES, California’s prescription drug monitoring program, and dose and quantity prescribed can be found at https://cures.doj.ca.gov. Please also confirm with the patient directly that they have been taking it as prescribed. If they have not been consistently taking the medication and have used other opioids, restarting the medication without treating it as a new induction increases the risk of precipitated withdrawal.

What if the patient has pain or will have surgery?

Continue their outpatient dose! Home buprenorphine or methadone can be split BID or TID to improve pain control, and additional non-opioid and opioid analgesics should be used. Buprenorphine and methadone will not prevent opioid analgesia from being effective. If the patient is on a stable dose of buprenorphine, receiving additional opioids will not put them at risk for precipitated withdrawal. See our perioperative and acute pain guidelines for further details.

My patient has renal impairment, can I continue/start buprenorphine, buprenorphine/naloxone or methadone?

Yes, neither buprenorphine, naloxone nor methadone are renally cleared to a clinically significant degree.

My patient has hepatic impairment, can I continue/start buprenorphine, buprenorphine/naloxone or methadone?

Both buprenorphine and naloxone are hepatically metabolized. Moderate and severe hepatic impairment prolong the half-lives of both buprenorphine and naloxone. If the combination product is used, however, the half-life of naloxone is prolonged to a greater degree than buprenorphine, which may rarely lead to accumulation and precipitated withdrawal. It is not recommended to use the combination product in severe hepatic impairment, and it should be used cautiously in moderate hepatic impairment. A buprenorphine solo product may be used cautiously in patients with hepatic impairment--generally however it is avoided if AST or ALT is > 5x the upper limit of normal.

The manufacturer of methadone does not provide guidance on dose adjustment in liver impairment. However, because methadone is metabolized by the liver, the half-life may be prolonged in moderate to severe liver impairment and dose reductions may be required.

What is the risk of precipitated withdrawal with buprenorphine initiations?

One of the primary concerns with initiating buprenorphine is precipitated withdrawal in patients who are currently tolerant to a full opioid agonist. This risk is mitigated with assessing recent opioid use and ensuring the patient is experiencing mild to moderate opioid withdrawal symptoms at the time of treatment (COWS ≥ 8 with some objective signs). Risk is highest if the patient is transitioning from methadone to buprenorphine. If a patient was recently hospitalized, incarcerated, or otherwise not using opioids for >7 days, but does have documented opioid use disorder, they may safely be started without risk of precipitated withdrawal.

A careful conversation with the patient about the risk of precipitated withdrawal may be necessary. If the patient is not currently in opioid withdrawal but is interested in medication-assisted treatment, referral to outpatient treatment with or without a prescription are still appropriate. One retrospective evaluation of buprenorphine initiated in a single ED reported no instances of precipitated withdrawal in 158 cases of initiation. Notably, this study included only patients who presented in active withdrawal.

If my patient is on buprenorphine, will opioid analgesics cause withdrawal or be ineffective for pain?

Although this is a common concern among patients on buprenorphine therapy, if a patient is currently taking buprenorphine, addition of a full opioid agonist does not precipitate withdrawal. Precipitated withdrawal only occurs in patients physically dependent on a full opioid agonist is given a partial opioid agonist or opioid antagonist. Once a patient has been taking buprenorphine, they may add opioid agonists without risking precipitated withdrawal with their next dose of buprenorphine. Given a patients opioid tolerance they may need higher doses of opioid analgesics than non dependent patients, but opioid analgesics should be effective.

How long do I need to observe a patient prior to discharge after a dose of buprenorphine?

Multiple studies have confirmed the safety and efficacy of home buprenorphine induction without direct observation. Low doses of buprenorphine should not cause respiratory depression in patients with known opioid tolerance. Monitoring following dosing inpatient or in the emergency department is only necessary for ensuring that the dose improved withdrawal, for about 1 hour.

Pharmacy

Buprenorphine isn’t available at my institution, how can I get it on formulary?

Most institutions allow for requests for formulary additions by providers within the system. This generally requires a provider on record to either develop or work with a member of the pharmacy staff to develop a drug monograph and presentation at a Pharmacy and Therapeutics (P&T) committee. We provide a template monograph for buprenorphine that can be adjusted to the specifications of your hospital system.

I’m caring for a patient taking buprenorphine/naloxone, but we only have the buprenorphine mono product (or vice-versa) at my institution, can I substitute?

Yes. Naloxone is added to deter injection of the buprenorphine. While these products are not considered “A” rated (therapeutically bioequivalent) by the FDA and cannot be interchanged by an outpatient pharmacy without a prescriber order, they can be considered clinically similar at equivalent dosages and frequencies. Continuation of a patient’s buprenorphine therapy should not be withheld due to lack of availability of a specific product as long as an equivalent dose is available.

How does a clinician give buprenorphine?

Buprenorphine tablets or films should be administered sublingually. IV formulations can also be used in some situations. If buprenorphine tablets or films are swallowed, very little medicine gets absorbed. No observation is required. Transdermal buprenorphine will generally be too weak to prevent withdrawal symptoms and is best used for patients with chronic pain.

What buprenorphine formulations are available for the treatment of opioid use disorder?

 
 

Referrals to Ongoing Care Following MOUD Starts from the Acute Care Setting

What should I have in place prior to discharging a patient who has been initiated on buprenorphine or methadone?

Because a discharge prescription will likely be needed, it is helpful to have one or more prescribers with a DATA 2000 x-waiver available during day shifts to prescribe buprenorphine.

Until a routine relationship is established with a local provider or clinic, it is recommended to call a local buprenorphine prescriber (see SAMHSA database at https://tinyurl.com/mtyjtm5) before buprenorphine starts to arrange an appointment for patient. Ideally, this appointment will be within 3 days of discharge.

Similarly, for methadone it is important to call an outpatient methadone clinic prior as soon as possible after admission to arrange for follow up. Physicians outside of these programs cannot prescribe methadone for addiction, therefore discharge prescriptions cannot be written by hospital providers.

What if there are not many outpatient buprenorphine or methadone prescribers in my community?

This is a challenge in many communities. As more providers are receiving their x-waivers, there are more communities where buprenorphine is easier to access outpatient than methadone, therefore may be a better choice logistically. In California, the Hub and Spoke project will be supporting local providers (“spokes”) in prescribing buprenorphine through close partnerships with expert “hubs.” Please see http://www.uclaisap.org/ca-hubandspoke/ for more information.

You can use the SAMHSA treatment finder to locate providers with X waivers in your community (https://tinyurl.com/mtyjtm5) and reach out to see if they would be able to accept your patients. If no providers are available in your community at this point, options like Groups (http://www.chcf.org/projects/2017/groups), Project Echo (https://echo.unm.edu/nm-teleecho-clinics/opioid/), and telemedicine prescribing such as through Bright Heart Health (https://www.brighthearthealth.com/) may be good options for building local capacity.

Federal Regulations

Title 21, Code of Federal Regulations, Part 1306.07(b)

72 HOUR RULE

(Title 21, Code of Federal Regulations, Part 1306.07(b), allows a practitioner who is not separately registered as a narcotic treatment program or certified as a “waivered DATA 2000 physician,” to administer (but not prescribe) narcotic drugs to a patient for the purpose of relieving acute withdrawal symptoms while arranging for the patient’s referral for treatment, under the following conditions: 1) not more than one day’s medication may be administered or given to a patient at one time? 2) this treatment may not be carried out for more than 72 hours and 3) this 72 hour period cannot be renewed or extended.

PART 1306 — PRESCRIPTIONS

GENERAL INFORMATION

§1306.07 Administering or dispensing of narcotic drugs.

(a) A practitioner may administer or dispense directly (but not prescribe) a narcotic drug listed in any schedule to a narcotic dependant person for the purpose of maintenance or detoxification treatment if the practitioner meets both of the following conditions:

(1) The practitioner is separately registered with DEA as a narcotic treatment program.

(2) The practitioner is in compliance with DEA regulations regarding treatment qualifications, security, records, and unsupervised use of the drugs pursuant to the Act.

(b) Nothing in this section shall prohibit a physician who is not specifically registered to conduct a narcotic treatment program from administering (but not prescribing) narcotic drugs to a person for the purpose of relieving acute withdrawal symptoms when necessary while arrangements are being made for referral for treatment. Not more than one day's medication may be administered to the person or for the person's use at one time. Such emergency treatment may be carried out for not more than three days and may not be renewed or extended.

(c) This section is not intended to impose any limitations on a physician or authorized hospital staff to administer or dispense narcotic drugs in a hospital to maintain or detoxify a person as an incidental adjunct to medical or surgical treatment of conditions other than addiction, or to administer or dispense narcotic drugs to persons with intractable pain in which no relief or cure is possible or none has been found after reasonable efforts.

(d) A practitioner may administer or dispense (including prescribe) any Schedule III, IV, or V narcotic drug approved by the Food and Drug Administration specifically for use in maintenance or detoxification treatment to a narcotic dependent person if the practitioner complies with the requirements of §1301.28 of this chapter.