BUPRENORPHINE/ NALOXONE FILM,SUBLINGUAL
Clinical Criteria Summary
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Perioperative Pain Management Principles
- Buprenorphine treatment should not be routinely discontinued in the perioperative period for patients on stable MOUD therapy.
- Discontinuation may confer medical risks including return to active opioid use (50-90%), risk of overdose, prolonged hospital stay, and increased patient burden.
- A buprenorphine taper to < 16 mg/day may be considered for patients prescribed higher doses (> 16 mg) with anticipated high post-surgical pain.
- Utilize a multimodal pain approach including systemic non-opioid analgesics (acetaminophen, NSAIDs, gabapentinoids, ketamine, magnesium, systemic lidocaine, alpha-2 agonists, glucocorticoids), regional/local analgesics, and psychosocial interventions.
- When a full μOR agonist is needed to adequately control perioperative pain, use opioids with similar lipophilicity and binding affinity toward μORs; fentanyl and hydromorphone are reasonable alternatives.
Pre-operative Assessment & Planning
- Perform patient evaluation including pain history, physical examination, medication reconciliation, assessment of physical/psychiatric comorbidities, and urine drug monitoring (including methadone, fentanyl, buprenorphine/metabolites).
- Verify prescription adherence via PDMP database.
- Conduct universal substance use disorder screening; perform detailed questioning and appropriate referrals for positive responses.
- Provide pre-operative counseling with written instructions regarding risks of opioid exposure/undertreating pain as relapse triggers.
- Determine procedure-related pain severity (minimal/no pain vs. significant pain) to guide dose adjustment or continuation.
- Plan continuity of care: taper off short-acting opioids prior to discharge; restrict IR opioids to short-term rescue use perioperatively; coordinate with waivered provider/OUD team for outpatient post-op pain care; preschedule follow-up with OUD/chronic pain provider; ensure sufficient buprenorphine supply at discharge.
Elective Procedure Management Criteria
- For most patients, continue buprenorphine throughout the operative period.
- Minimally painful surgery: Continue current home dose unchanged, or divide and administer every 6 to 8 hours. Total daily dose may be titrated up to 32 mg/day in divided doses if needed for pain management (does not apply to extended-release injection).
- Painful surgery (moderate/severe pain): Continue baseline dose > 16 mg/day, OR reduce to < 16 mg/day to allow addition of an IR full μOR agonist. Expect higher doses of full μOR agonists requiring close monitoring (e.g., ICU or step-down unit).
- Examples of minimal pain procedures: tooth extraction, endoscopy, colonoscopy, bronchoscopy.
- Examples of moderate/severe pain procedures: laparoscopic, intra-abdominal, intra-thoracic, and orthopedic procedures.
Emergent Procedure Management Criteria
- Anticipated minimal to no pain: Continue buprenorphine throughout procedure with non-opioid medications. Dose may be increased until adequate pain relief is achieved. Taper off short-acting opioids prior to discharge.
- Anticipated moderate to severe pain (Continue method): Continue buprenorphine throughout operation; increase dose postoperatively (except implant or BUP XR INJ) or use short-acting opioids. Taper off short-acting opioids prior to or shortly after discharge.
- Anticipated moderate to severe pain (Discontinue method): Discontinue per specified discontinuation criteria.
Discontinuation Criteria & Management
- Discontinuation is indicated only when: patient requests to stop (after discussing pros/cons with provider and OUD team); medical contraindication exists; or all other options (maximizing dose, splitting dose, multimodal therapy) are insufficient.
- Emergency procedures: Discontinue immediately upon admission in lieu of high-dose short-acting μOR agonist.
- Elective procedures: Discontinue 24-72 hours prior to surgery. Restart after resolution of acute postoperative pain.
- Monitor respiratory function when using high doses of full μOR agonists as buprenorphine clears; adjust doses to prevent opioid-induced respiratory depression (OIRD).
- Use short-acting full opioid agonists to mitigate withdrawal symptoms. Non-opioid adjuncts for withdrawal (alpha-2 receptor agonists, loperamide, ondansetron, diphenhydramine) may be used as appropriate.
Restarting Buprenorphine Criteria
- Taper off short-acting opioid and convert back to previous buprenorphine dose in consultation with waivered provider/OUD team.
- Restart when initial withdrawal signs are observed (for clinic induction) or by patient (for home induction).
- Initial dosing: 2 mg or 4 mg. If withdrawal is alleviated, restart remaining prior maintenance dose on day 1.
- Re-induction protocol: Start when clear signs of opioid withdrawal are present. Begin with 2-4 mg dose or 2/0.5 to 4/1 mg buprenorphine/naloxone. After approximately 2 hours, administer additional 2-4 mg if continued withdrawal and lack of sedation.
- FDA label maximum: 8 mg on Day 1 and 16 mg on Day 2. Document clinical rationale for dosing outside FDA recommendations. Individualize dosing; some patients stabilize on lower doses.
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Indications & Pharmacological Properties
- Approved for management of pain severe enough to require around-the-clock, long-term opioid treatment.
- Functions as a partial agonist at mu-opioid receptors (MORs) and antagonist at kappa-opioid receptors (KORs).
- Exhibits high binding affinity toward MORs with an extremely slow dissociation rate, making it difficult to displace from receptors once bound.
Perioperative Management
- Maximize all other non-opioid and non-pharmacological interventions for pain control.
- When a full MOR agonist is clinically necessary, utilize opioids with similar lipophilicity and binding affinity toward MORs (e.g., fentanyl, sufentanil, hydromorphone) to more effectively compete with buprenorphine.
- Consult waivered providers or an interdisciplinary team experienced with buprenorphine use when available.
- Communicate treatment plans directly with the buprenorphine prescriber to facilitate optimal transition of care postoperatively.
Discharge Planning & Continuity of Care
- Schedule patients with their SUD provider or chronic pain provider after discharge for close follow-up.
- Provide a warm hand-off for continued buprenorphine adherence upon discharge, particularly for high-risk patients.
- Discharge patients with an adequate supply of buprenorphine to last until their next scheduled follow-up appointment.
Naloxone Education & Counseling
- Evaluate the necessity of naloxone based on the specific indication for buprenorphine prescription.
- For buprenorphine buccal film prescribed for chronic pain without a history of OUD or other SUD and with minimal risk for abusing other opioids, naloxone may not be required unless immediate-release (IR) opioids are initiated postoperatively with plans to discharge on them.
- Conduct overdose education during hospitalization and prescribe naloxone at discharge for patients considered at risk for opioid overdose.
- Provide explicit instruction to patients on how to use the prescribed naloxone product.
Safety Screening
- Assess all patients for suicidal ideation prior to discharge per VA strategy and facility protocol.
- Recognize that chronic pain, history of or active SUD/OUD, acute stresses to health, and behavioral health comorbidities (e.g., depression, anxiety, PTSD) significantly heighten suicide risk.
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Patient Identification & Surgical Classification
- Surgical team/PreOP Clinic identifies patient on buprenorphine (Butrans®, Suboxone®, Subutex®, Zubsolv®, Belbuca® , Temgesic® , Sublocade ® , Buprenex®)
- Classify surgery as minimally painful or painful
Minimally Painful Surgery Criteria
- NO or minimal need for postop opioid therapy expected (e.g., endoscopy, cataracts)
- Continue home dose through procedure day and after discharge
- Avoid discontinuation or holding of buprenorphine doses
Painful Surgery & Dose Stratification
- High-dose patients: > 16 mg/day Suboxone/Subutex, > 11.4 mg/day Zubsolv
- Low-dose patients: < 16 mg/day Suboxone/Subutex, < 11.4 mg/day Zubsolv, Transdermal Buprenorphine (Butrans Patch) or Buccal Film (Belbuca), ANY DOSE
- No preoperative dose adjustment required for specified doses
Pre-operative Management
- Elective surgery: Contact buprenorphine prescriber to discuss dose continuation or gradual dose reduction in anticipation of elective surgery
- Pre-operative dose adjustment not possible: Schedule PreOP Clinic appointment within 2-4 weeks, not later than one week before surgery
- Management options: Continue BUP method (preferred) or Discontinue BUP method
- Anticipate need for high doses of opioids for better pain coverage, or dose reduction to <16 mg/day Suboxone/Subutex, <11.4mg/day Zubsolv by time of surgery
- Update and record prescriber name and contact information in PreOP Clinic
- Consult acute pain service IF expected inpatient stay
Day of Surgery / Intraoperative Management
- Perioperative plan per OR Anesthesia team / Acute Pain Team (if available)
- Use non-opioid analgesics (gabapentin, pregabalin, acetaminophen, NSAIDS) pre-operatively if not contraindicated
- Use continuous regional anesthesia techniques if possible (epidural and peripheral nerve catheters)
- Use IV ketamine, lidocaine intra-operatively if not contraindicated
Postoperative Management
- Pain Service will follow patients postoperatively if needed; pain management plan per Pain Service recommendations
- Maintenance or placement of axial or peripheral nerve catheters, or short-term nerve blocks as necessary
- Focus on non-opioid medication (gabapentinoids, acetaminophen, NSAIDs, antidepressants, α2 agonists etc.)
- Use full agonist opioid with high binding affinity (hydromorphone, fentanyl, or sufentanil) orally, IV, or by PCA
- Avoid use of long-acting opioids
- Continuation of buprenorphine at home dose, lower dose, or higher dose
- Consider Ketamine infusion protocol (1-5mcg/kg/min infusion) if applicable
- Use Non-medication/non-procedural adjuncts (acupuncture, pet therapy, PT and mechanical supports as appropriate)
Re-induction Planning
- Re-induction planning should not be necessary if patients continued to take buprenorphine during hospital stay or were on buprenorphine formulations for pain management (transdermal patch or buccal film)
- If buprenorphine was discontinued, pain service attending decides, in collaboration with buprenorphine prescriber or X-waivered provider, which re-induction strategy is appropriate
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Indications & Clinical Appropriateness
- FDA-approved for management of moderate to severe chronic pain requiring a continuous, around-the-clock opioid analgesic for an extended period of time.
- Appropriate when there is lack of progress towards functional goals and/or inadequate analgesic benefit with full mu agonist opioid.
- Appropriate when high potential for adverse effects exists due to medical conditions, mental health, or behavioral considerations with full mu agonist LTOT.
- Preferred for patients assessed as high risk for traditional oral opioid therapy where alternate buprenorphine products are not advisable, or for patients with documented difficulty swallowing/poor or unpredictable gastrointestinal absorption.
- More appropriate than transdermal patch for moderate MEDD dosing conversions (50-90 MEDD).
Contraindications & Inappropriateness
- Infrequent use of immediate-release opioid medication for episodic pain (e.g., PRN).
- Demonstrating functional improvement and expressing preference to remain on full agonist LTOT, in absence of medical, mental health, or behavioral risk for adverse effects.
- May not provide adequate analgesia for patients requiring greater than 160 mg oral morphine equivalent daily dose (MEDD); consider alternate analgesic.
- Not indicated as an as-needed (PRN) analgesic.
Dosing & Administration Guidelines
- Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
- For opioid-naïve/non-tolerant patients: Initiate with 75 mcg film once daily or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg every 12 hours.
- Titrate in increments of 150 mcg every 12 hours, no more frequently than every 4 days, to achieve adequate analgesia while minimizing adverse reactions.
- Initial dosing based on prior opioid expressed as oral MEDD: <30 mg MEDD (75 mcg qd or q12h), 30-89 mg MEDD (150 mcg q12h), 90-160 mg MEDD (300 mcg q12h).
- Discontinue all other around-the-clock opioid drugs when BUP BF therapy is initiated.
- For oral buccal use only; apply to the buccal mucosa every 12 hours.
- Wait at least one hour after taking before brushing teeth; swish gently and swallow after dissolution.
- Do not apply to areas of the mouth with open sores or lesions.
- Do not use if pouch seal is broken or film is cut/damaged.
Initiation & Transition Strategies
- Follow FDA-approved labeling for new starts and standard opioid transitions.
- STOP-START method: Stop full agonist opioids for 12-24 hours and start buprenorphine in early stages of withdrawal to decrease risk of precipitated withdrawal.
- Low dose buprenorphine initiation (microdosing/overlapping dosing): Allows short-term overlap of buprenorphine titration while on full agonist to mitigate withdrawal and discomfort.
- Published conversion recommendations are highly conservative (reduced 50-75%) and already include reduction for lack of tolerance or cross-tolerance.
- Avoid rapid titrations without assessing effectiveness and tolerability at steady state; due to long half-life, takes about five days to achieve steady state.
Monitoring, Evaluation & Safety Considerations
- LTOT principles should be followed: focus on functional improvement in physical, social, and psychological domains consistent with the biopsychosocial model of care.
- Assess risks versus benefits periodically; tapering or discontinuing should be considered when risks outweigh benefits or based on patient preference.
- Screen for and assess risk for OUD prior to initiation and when patterns of unhealthy medication use emerge during LTOT.
- Baseline evaluation includes: Urine drug screen (UDS), PDMP check, liver transaminases, monitor for effectiveness of pain relief/prevention of withdrawal symptoms, assess risk for physical/psychological dependence, drug diversion, sensitivity to adverse effects (particularly respiratory depression), assess mental status/respiratory status/increased risk for falls.
- Pain Management Teams (PMT) should be available for specialty care support during initiation/stabilization and transitions.
- Shared decision-making and veteran preference should guide treatment approach.
- For patients without diagnosed OUD, the encounter should indicate the pain condition diagnosis and the prescription should state “for pain management”.
Patient Counseling & Special Instructions
- Caution with driving or operating heavy machinery.
- Store in secure place out of reach of children.
- Advise patients to avoid eating or drinking until film dissolves.
- Inform dentist that therapy has been started; wait at least one hour after taking before brushing teeth.
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Indications
- Acute pain
- Intractable pain
- Pain expected to be severe enough to require opioid management
Patient Selection (Appropriate)
- Veterans who may be appropriate for a usual formulary opioid (e.g., fentanyl, hydromorphone, oxycodone, morphine) for acute pain management
- Veterans with known risk factors for hospital Opioid Related Adverse Events (ORADES)
- Veterans already on a buprenorphine pain formulation as an outpatient (e.g., buccal or transdermal)
- Veterans with impaired renal function (dose adjustment not required)
- Veterans who are opioid naïve with other medical risks (e.g., COPD, advanced age)
- Veterans at high risk for opioid dependence (e.g., co-occurring chronic pain syndromes)
- Patients more sensitive to the GI side effects of opioids and surgical procedures
Patient Selection (Inappropriate/Not Recommended)
- Pain not severe enough (or expected to be severe enough) to require opioid therapy
- Patients already on high-dose opioid therapy (prescribed or illicit) or long-acting opioid antagonist treatment (e.g., Vivitrol) due to unknown exact role of pain formulations at this time
Contraindications & Precautions
- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting
- Known or suspected GI obstruction including paralytic ileus
- Hypersensitivity to buprenorphine
- Additive risk with concomitant CNS depressants (similar to other full-agonist opioids)
Dosing & Administration Criteria
- Pre/Peri-operative and PACU: 0.3 mg slow IV (over 2 minutes) pre-op; repeat 0.3 mg slow IV during PACU recovery PRN, may repeat x1 additional dose at 30 minutes if necessary
- PACU to Ward: If IV effective, consider continuing transmucosal formulation (e.g., Belbuca 300 to 450 mcg BID) scheduled for duration of admission; dose adjust based on observed patient response
- Discharge Home: If effective and additional discharge opioids indicated, consider continuing buprenorphine buccal 2-3 times daily PRN for expected post-surgical duration; select outpatient dose based on observed effective minimum dose during inpatient episode
- Emergency Department: Primarily transmucosal; specific use guidance outside scope but studied in renal colic and fractures
- Patients on milligram doses of buprenorphine (8-32 mg/day or LAI): Should NOT be stopped for acute pain management where FAO may be used; continue at maintenance dose and add non-opioid/high-potency FAO as needed. Dose reduction (25-50%) may be considered to allow mu-opioid receptors to “open up” in 12-24 hours, but requires close monitoring due to increased risk of overdose/withdrawals
Clinical Management & Pearls
- Tapering and discontinuing buprenorphine for acute pain should not be needed; self-tapers due to long half-life. Advise patients to stop if pain is well managed with non-opioid only
- Onset of action: within 20 minutes (faster with parenteral); full effect of transmucosal products may take 1-3 hours
- Buccal formulation benefits from mucoadherence; requires no patient participation; can be administered under anesthesia; dry buccal mucosa can be moistened with a gloved finger prior to application; yellow side goes on cheek; do not eat or drink while dissolving; rinse mouth after complete dissolution
- If buprenorphine is ineffective/insufficient: may indicate opioid refractoriness; optimize non-opioid strategies and use high-potency full-agonist opioids (FAO); conventional FAO expected to be fully effective even if microgram doses prove ineffective
- Precipitated withdrawal: Microgram dosing for acute pain would not be expected to result in precipitated withdrawal; incidence <5% even when transitioning from high-dose full-agonists