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Reframe severe and persistent pain treatment with BELBUCA®*
(buprenorphine buccal film)

BELBUCA has 7 dose strengths, allowing for flexible dosing options to reach optimal dose¹

Titrate BELBUCA to a dose that provides adequate analgesia and minimizes adverse reactions.¹ Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals.

BELBUCA available in 7 dose strengths: 75 mcg, 150 mcg, 300 mcg, 450 mcg, 600 mcg, 750 mcg, 900 mcg with the first three noted as starting doses.

Serious, life-threatening, or fatal respiratory depression may occur, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of BELBUCA are essential.

A 3-step approach to starting and titrating to an optimal dose

Learn more

Use the MME Conversion Calculator to determine appropriate starting dose and potential titration steps

BELBUCA is different from transdermal buprenorphine1,2:

BELBUCA offers more dosing options and strengths than the transdermal patch—with a higher bioavailability of buprenorphine.1-4

BELBUCA was studied in a patient population with moderate to severe chronic low back pain and prior opioid use. BELBUCA was studied in patients up to 160 MME

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The transdermal patch was studied in patients up to 80 MME

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There are no head-to-head studies between BELBUCA and other opioids

BELBUCA1,3
Transdermal buprenorphine2,4
Total daily dose of prior opioid†
0-160 MME
0-80 MME
Bioavailability
46%–65%
~15%
Total no. of dose strengths
7
5
Maximum dose
900 mcg
20 mcg/hr
Dosing interval
q12h
q7d
Titration interval
4 days
3 days
Method of application
Apply to inside of cheek every 12 hours. Typically dissolves in 30 minutes
Apply to skin at 1 of 8 designated sites every 7 days. Do not apply to same site for 21 days

There are no head-to-head studies comparing pharmacokinetics, bioavailability, safety, and efficacy of the 2 products.

Table is based on information included in the full Prescribing Information for each product.
Transdermal buprenorphine hourly dosing: 0.005 mg/hr; 0.0075 mg/hr; 0.01 mg/hr; 0.015 mg/hr; 0.02 mg/hr.

†Total daily MME of the opioid medications patients took prior to enrolling in clinical trials.

MME=morphine milligram equivalent.

Starting your patients on BELBUCA

A 3-step approach to starting your patient on BELBUCA and titrating to an optimal dose¹

There are 7 dose strengths to identify your patient's optimal dose for treating severe and persistent pain1*

Identify current daily opioid MME dose and taper it to ≤30-mg oral MME daily1

IDENTIFY CURRENT DAILY MME AND TAPER DOWN
<30-mg oral MME
30- to 89-mg oral MME
90- to 160-mg oral MME
Taper opioid-experienced patients' current opioid dose to ≤30-mg MME daily

No CDC MME conversion factor with buprenorphine5

CDC MME guidelines provide direction but should not replace clinical judgment. Refer to your state-specific guidelines regarding MME conversions.During taper and titration, patients may need additional short-acting analgesics. Individualized supplementary options, like short-acting opioids or nonopioids, should only be decided upon in consultation with an HCP. During the taper phase of the double-blind, placebo-controlled study, opioid-experienced patients were permitted to use HC/APAP 5 mg/325 mg (PRN q6h with a maximum of 4 tablets per day) as analgesic rescue.

In patients with severe hepatic impairment or with known or suspected mucositis, reduce starting and titration dose by half that of patients with normal liver function or without mucositis.

CDC=Centers for Disease Control and Prevention; HC/APAP=hydrocodone/acetaminophen; MME=morphine milligram equivalent; PRN=as needed.

Determine appropriate BELBUCA starting dose based on patient's total daily opioid dose prior to taper1

FIND PREVIOUS DOSE
DETERMINE BELBUCA STARTING DOSE
<30-mg oral MME
75 mcg† QD or q12h
30- to 89-mg oral MME
150 mcg q12h
90- to 160-mg oral MME
300 mcg q12h

Q12h=every 12 hours; QD=once daily.

†For opioid-naive and opioid-intolerant patients, begin at 75 mcg QD or q12h.

When BELBUCA therapy is initiated, discontinue all other opioid analgesics other than those used on an as-needed basis for breakthrough pain when appropriate.

There is interpatient variability in the relative potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of BELBUCA. It is safer to underestimate a patient's 24-hour oral buprenorphine dosage and provide rescue medication (eg, immediate-release opioid) than to overestimate the 24-hour buprenorphine dosage and manage an adverse reaction due to overdose.

Proceed with titration in increments of 150 mcg until patient reaches optimal dose1

BELBUCA® Starting Dose
TiTrate to optimal dose with appropriate q12h doses§¶
1
2
3
4
5
6
75 mcg‡ QD or q12h
150 mcg
300 mcg
450 mcg
600 mcg
750 mcg
900 mcg
150 mcg q12h
300 mcg
450 mcg
600 mcg
750 mcg
900 mcg
300 mcg q12h
450 mcg
600 mcg
750 mcg
900 mcg

BELBUCA can be titrated as often as every 4 days until patients reach their optimal dose.1

Regular evaluation is of particular importance when converting from methadone to other opioid agonists, including BELBUCA. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

In the clinical trials, optimal dose6 was defined as a dose satisfactory for both analgesia and tolerability:

Without the need
for rescue medication
OR
With no more than 2 tablets
of HC/APAP per day

‡Titration should occur no more frequently than every 4 days, with doses in q12h intervals.

§Only doses up to 450 mcg q12h were studied in opioid-naive patients. For opioid-naive and opioid-intolerant patients, begin at 75 mcg QD or q12h for at least 4 days before continuing in increments of 150 mcg q12h.

Maximum dose is 900 mcg every 12 hours. Do not exceed due to the potential for QTc interval prolongation. If pain is not managed at this maximum dose, or for patients previously taking >160 MME, consider an alternate analgesic.

Individually titrate BELBUCA to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving BELBUCA to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for the development of addiction, abuse, or misuse. Monitor patients closely with use of BELBUCA, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of BELBUCA are essential.

Calculating the BELBUCA Starting Dose: Use the MME conversion calculator

How to use the MME Conversion Calculator:

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Determine current daily MME, then taper current opioid dose to 30-mg oral MME daily

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Use the MME conversion calculator provided to determine the appropriate BELBUCA starting dose based on the patient's total daily opioid dose prior to taper

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For opioid-naive and opioid-intolerant patients, begin at 75 mcg QD or q12h for at least 4 days before continuing in increments of 150 mcg q12h

Note: There is no associated CDC MME conversion factor with buprenorphine. CDC MME guidelines are for guidance only and are not a substitute for clinical decision making. Refer to your state-specific guidelines regarding MME conversions.5

A conservative approach is advised when determining the total daily dosage of BELBUCA. The MME Conversion Calculator should not be used as a substitute for clinical judgment.

MME Conversion Calculator Interface

Establishing the Morphine Milligram Equivalents

The Opioid Conversion Guide provided here contains a summary of information from the Centers for Disease Control and Prevention (CDC) on opioids and their oral morphine milligram equivalent (MME) conversion factors.

Opioid Conversion Guide

Conversion tools are not a substitute for clinical decision making. Assess patient’s risk for opioid addiction, abuse, or misuse prior to prescribing BELBUCA and reassess regularly for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as BELBUCA, but use in such patients necessitates intensive counseling about the risks and proper use of BELBUCA, along with intensive monitoring for signs of addiction, abuse, or misuse.

References:

1. BELBUCA [Prescribing Information]. Stoughton, MA: Collegium Pharmaceutical, Inc.; December 2023. 2. BUTRANS [Prescribing Information]. Stamford, CT: Purdue Pharma L.P. December 2023. 3. Priestley T, et al. Pain Med. 2018;19(10):1988-1996. 4. Wang Y, et al. J Clin Pharmacol. 2016;56(10):1263-1271. 5. Dowell D, Ragan K, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain. MMWR. 2022;71(3):1-95. 6. Hale M, Urdaneta V, Kirby MT, Xiang Q, Rauck R. Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids. J Pain Res. 2017;10:233-240. 7. US Department of Health and Human Services. Opioid oral morphine milligram equivalent. Accessed August 9, 2022. https://www.hhs.gov/guidance/document/opioid-oral-morphine-milligram-equivalent-mme-conversion-factors-0

IMPORTANT SAFETY INFORMATION ABOUT BELBUCA®

INDICATION

*BELBUCA® (buprenorphine buccal film) is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.

Limitations of Use

  • Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations, reserve BELBUCA for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
  • BELBUCA is not indicated as an as-needed (prn) analgesic.

IMPORTANT SAFETY INFORMATION ABOUT BELBUCA® (cont’d)
CONTRAINDICATIONS

BELBUCA is contraindicated in patients with significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; and hypersensitivity (e.g., anaphylaxis) to buprenorphine.

WARNINGS AND PRECAUTIONS

Addiction, Abuse, and Misuse

  • BELBUCA contains buprenorphine, a Schedule III controlled substance. As an opioid, BELBUCA exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed BELBUCA. Addiction can occur at recommended dosages and if the drug is misused or abused.
  • Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing BELBUCA and reassess all patients receiving BELBUCA for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as BELBUCA, but use in such patients necessitates intensive counseling about the risks and proper use of BELBUCA, along with frequent reevaluation for signs of addiction, abuse, or misuse.
  • Consider prescribing naloxone for the emergency treatment of opioid overdose.
  • Abuse or misuse of BELBUCA by swallowing may cause choking, overdose, and death.

IMPORTANT SAFETY INFORMATION ABOUT BELBUCA®

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF BELBUCA

Addiction, Abuse, and Misuse

BELBUCA exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of BELBUCA, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of BELBUCA are essential. Misuse or abuse of BELBUCA by chewing, swallowing, snorting, or injecting buprenorphine extracted from the buccal film will result in the uncontrolled delivery of buprenorphine and poses a significant risk of overdose and death.

Accidental Exposure

Accidental exposure to even one dose of BELBUCA, especially in children, can result in a fatal overdose of buprenorphine.

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of BELBUCA and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.

Neonatal Opioid Withdrawal Syndrome (NOWS)

If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription.

  • Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing BELBUCA. Strategies to reduce the risk include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and the proper disposal of unused drug. Contact local state professional licensing board or state-controlled substance authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression

  • Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
  • While serious, life-threatening or fatal respiratory depression can occur at any time during the use of BELBUCA, the risk is greatest during initiation of therapy or following a dosage increase.
  • To reduce the risk of respiratory depression, proper dosing and titration of BELBUCA are essential. Overestimating the dose of BELBUCA when converting patients from another opioid product may result in fatal overdose with the first dose.
  • Accidental exposure to BELBUCA, especially in children, can result in respiratory depression and death due to an overdose of buprenorphine.
  • Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose.
  • Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose:

  • Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with BELBUCA. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered.
  • Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone.

Risks due to Interactions with Benzodiazepines or Other Central Nervous System Depressants

  • Profound sedation, respiratory depression, coma, and death may result from the concomitant use of BELBUCA with benzodiazepines or other CNS depressants including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
  • Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.
  • If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Inform patients and caregivers of this potential interaction and educate them on signs and symptoms of respiratory depression (including sedation).
  • If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose.
  • Advise both patients and caregivers about the risks of respiratory depression and sedation when BELBUCA is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

Neonatal Opioid Withdrawal Syndrome (NOWS)

  • Use of BELBUCA for an extended period of time during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of NOWS and manage accordingly. Advise pregnant women using opioids for an extended period of the risk of NOWS and ensure that appropriate treatment will be available.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

  • To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers.

Healthcare providers are strongly encouraged to do all of the following:

  • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
  • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.
  • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
  • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.

To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

Opioid-Induced Hyperalgesia and Allodynia

  • Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.
  • Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching the patient to a different opioid moiety).

Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cathectic, or Debilitated Patients

  • The use of BELBUCA in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
  • BELBUCA-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive, including apnea, even at recommended dosages of BELBUCA.
  • Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
  • Regularly evaluate patients, particularly when initiating and titrating BELBUCA and when BELBUCA is given concomitantly with other drugs that depress respiration.

Adrenal Insufficiency

  • Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include nonspecific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Severe Hypotension

  • BELBUCA may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Regularly evaluate these patients for signs of hypotension after initiating or titrating the dosage of BELBUCA. In patients with circulatory shock, BELBUCA may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of BELBUCA in patients with circulatory shock.

Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

  • In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), BELBUCA may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with BELBUCA.
  • Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of BELBUCA in patients with impaired consciousness or coma.

Hepatotoxicity

  • Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving sublingual formulations of buprenorphine for the treatment of opioid dependence, both in clinical trials and in postmarketing adverse events reports. For patients at increased risk of hepatotoxicity (e.g., patients with a history of excessive alcohol intake, intravenous drug abuse or liver disease), obtain baseline liver enzyme levels and periodically reassess during treatment with BELBUCA.

Risk of Use in Patients with Gastrointestinal Conditions

  • BELBUCA is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
  • BELBUCA may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Regularly evaluate patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Increased Risk of Seizures in Patients with Seizure Disorders

  • The buprenorphine in BELBUCA may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures occurring in other clinical settings associated with seizures. Regularly evaluate patients with a history of seizure disorders for worsened seizure control during BELBUCA therapy.

Dental Adverse Events

  • Cases of dental caries, some severe (i.e., tooth fracture, tooth loss), have been reported following the use of transmucosal buprenorphine-containing products. Reported events include cavities, tooth decay, dental abscesses/infection, rampant caries, tooth erosion, fillings falling out, and, in some cases, total tooth loss. Treatment for these events included tooth extraction, root canal, dental surgery, as well as other restorative procedures (i.e., fillings, crowns, implants, dentures). Multiple cases were reported in individuals without any prior history of dental problems.
  • Refer patients to dental care services and encourage them to have regular dental checkups while taking BELBUCA. Educate patients to seek dental care and strategies to maintain or improve oral health while being treated with transmucosal buprenorphine containing products. Strategies include, but are not limited to, gently rinsing the teeth and gums with water and then swallowing after BELBUCA has been completely dissolved in the oral mucosa. Advise patients to wait for at least one hour after taking BELBUCA before brushing teeth.

QTc Prolongation

  • Thorough QT studies with buprenorphine products have demonstrated QT prolongation ≤15 msec. This QTc prolongation effect does not appear to be mediated by hERG channels. Based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors. The risk of combining buprenorphine with other QT-prolonging agents is not known.
  • Consider these observations in clinical decisions when prescribing BELBUCA to patients with risk factors such as hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, or severe hypomagnesemia.

Anaphylactic/Allergic Reactions

  • Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported.

Withdrawal

  • Do not abruptly discontinue BELBUCA in a patient physically dependent on opioids. When discontinuing BELBUCA in a physically dependent patient, gradually taper the dosage. Rapid tapering of buprenorphine in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.
  • Additionally, the use of BELBUCA, a partial agonist opioid analgesic, in patients who are receiving a full opioid agonist analgesic may reduce the analgesic effect and/or precipitate withdrawal symptoms. Avoid concomitant use of BELBUCA with a full opioid agonist analgesic.

Risks of Driving and Operating Machinery

  • BELBUCA may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to side effects of BELBUCA and know how they will react to the medication.

Risk of Overdose in Patients with Moderate or Severe Hepatic Impairment

  • In a pharmacokinetic study of subjects dosed with buprenorphine sublingual tablets, buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment. For patients with severe hepatic impairment, a dose adjustment is recommended, and patients with moderate or severe hepatic impairment should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine.

Risks of Use in Cancer Patients with Oral Mucositis

  • Cancer patients with oral mucositis may absorb buprenorphine more rapidly than intended and are likely to experience higher plasma levels of the opioid. For patients with known or suspected mucositis, a dose reduction is recommended. Regularly evaluate these patients carefully for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine.

ADVERSE REACTIONS

  • The most common adverse reactions (≥5%) reported by patients treated with BELBUCA in the clinical trials were nausea, constipation, headache, vomiting, fatigue, dizziness, and somnolence.

See full Prescribing Information, including Boxed Warning on Addiction, Abuse and Misuse and other serious risks, accompanying this piece or at BELBUCA.com/pi.

To report SUSPECTED ADVERSE REACTIONS, contact Collegium Pharmaceutical, Inc. at 1-855-331-5615 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.