Drug Detail:Belbuca (Buprenorphine (oral/buccal) [ bue-pre-nor-feen ])
Generic Name: buprenorphine hydrochloride 75ug
Dosage Form: buccal film
Drug Class: Opioids (narcotic analgesics)
Important Dosage and Administration Instructions
BELBUCA should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
- Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].
- Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)].
- Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with BELBUCA and adjust the dosage accordingly [see Warnings and Precautions (5.3)].
BELBUCA buccal film is for oral buccal use only and is to be applied to the buccal mucosa every 12 hours.
Instruct patients not to use BELBUCA if the pouch seal is broken or the buccal film is cut, damaged, or changed in any way and to avoid applying BELBUCA to areas of the mouth with any open sores or lesions.
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 [see Warnings and Precautions (5.3), Patient Counseling Information (17)].
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).
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 [see Warnings and Precautions (5.1, 5.3, 5.5)].
Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.
Initial Dosing
Use of BELBUCA as the Initial Opioid Analgesic (opioid-naïve patients) or in Patients who are not Opioid Tolerant (opioid-non-tolerant patients)
Initiate treatment in opioid-naïve and opioid-non-tolerant patients with a 75 mcg film once daily or, if tolerated, every 12 hours (see Table 1) for at least 4 days, then increase dose to 150 mcg every 12 hours. Individual titration to a dose that provides adequate analgesia and minimizes adverse reactions should proceed in increments of 150 mcg every 12 hours, no more frequently than every 4 days. Doses up to 450 mcg every 12 hours were studied in opioid-naïve patients in the clinical trials [see Clinical Studies (14)].
Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression [see Warnings and Precautions (5.3)].
Conversion from Other Opioids to BELBUCA
Discontinue all other around-the-clock opioid drugs when BELBUCA therapy is initiated.
There is a potential for buprenorphine to precipitate withdrawal in patients who are already on opioids. To reduce the risk of opioid withdrawal, taper patients to no more than 30 mg oral morphine sulfate equivalents (MSE) daily before beginning BELBUCA. Following analgesic taper, base the starting dose on the patient's daily opioid dose prior to taper, as described in Table 1. Patients may require additional short-acting analgesics during the taper period and during titration.
BELBUCA may not provide adequate analgesia for patients requiring greater than 160 mg oral MSE per day. Consider the use of an alternate analgesic.
There is inter-patient 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 (e.g., immediate-release opioid) than to overestimate the 24-hour buprenorphine dosage and manage an adverse reaction due to overdose.
In a BELBUCA clinical trial with an open-label titration period, patients were converted from their prior opioid to BELBUCA using Table 1 as a guide for the initial BELBUCA dose.
| Prior Daily Dose of Opioid Analgesic Before Taper to 30 mg Oral MSE | Initial BELBUCA Dose |
|---|---|
| Less than 30 mg oral MSE | BELBUCA 75 mcg once daily or every 12 hours |
| 30 mg to 89 mg oral MSE | BELBUCA 150 mcg every 12 hours |
| 90 mg to 160 mg oral MSE | BELBUCA 300 mcg every 12 hours |
| Greater than 160 mg oral MSE | Consider alternate analgesic |
BELBUCA doses of 600 mcg, 750 mcg, and 900 mcg are only for use following titration from lower doses of BELBUCA. Individual titration should proceed in increments of 150 mcg every 12 hours, no more frequently than every 4 days.
Conversion from Methadone to BELBUCA
Close monitoring 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.
Titration and Maintenance of Therapy
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 and the relative incidence of adverse reactions and monitor for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics.
Patients who experience breakthrough pain may require dosage adjustment of BELBUCA or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the BELBUCA dose.
The minimum titration interval of BELBUCA is 4 days, based on the pharmacokinetic profile and time to reach steady-state plasma levels [see Clinical Pharmacology (12.3)]. Individual titration should proceed in increments of no more than 150 mcg every 12 hours.
The maximum BELBUCA dose is 900 mcg every 12 hours. Do not exceed a dose of BELBUCA 900 mcg every 12 hours due to the potential for QTc interval prolongation [see Warnings and Precautions (5.13), Adverse Reactions (6.1), Clinical Pharmacology (12.2)]. If pain is not adequately managed on BELBUCA 900 mcg, consider an alternate analgesic.
If unacceptable opioid-related adverse reactions are observed, adjust the dose to obtain an appropriate balance between the management of pain and opioid-related adverse reactions.
Safe Reduction or Discontinuation of BELBUCA
Do not abruptly discontinue BELBUCA in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.
When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking BELBUCA, there are a variety of factors that should be considered, including the dose of BELBUCA the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication-assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist.
There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on BELBUCA who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.
When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.15), Drug Abuse and Dependence (9.3)].
Dosage Modifications in Patients with Severe Hepatic Impairment
In patients with severe hepatic impairment (i.e., Child-Pugh C), reduce the starting dose and reduce the titration dose by half that of patients with normal liver function, from 150 mcg to 75 mcg [see Warnings and Precautions (5.11), Use in Special Populations (8.6), Clinical Pharmacology (12.3)].
Dosage Modifications in Patients with Oral Mucositis
In patients with known or suspected mucositis, reduce the starting dosage and titration incremental dosage by half compared to patients without mucositis [see Warnings and Precautions (5.18), Clinical Pharmacology (12.3)].
Administration of BELBUCA
BELBUCA should not be used if the package seal is broken or the film is cut, damaged, or changed in any way.
First, the patient must use the tongue to wet the inside of the cheek or rinse the mouth with water to wet the area for placement of BELBUCA. BELBUCA is then applied immediately after removal from the individually sealed package. The yellow side of the BELBUCA film is placed against the inside of the cheek. The entire BELBUCA film is held in place with clean, dry fingers for 5 seconds and then left in place on the inside of the cheek until fully dissolved.
BELBUCA adheres to the moist buccal mucosa and will completely dissolve after application, usually within 30 minutes. The film should not be manipulated with the tongue or finger(s) and eating food and drinking liquids should be avoided until the film has dissolved.
Advise patients to do the following after the product has completely dissolved in the oral mucosa: take a sip of water, swish gently around the teeth and gums, and swallow. Advise patients to wait for at least one hour after taking BELBUCA before brushing teeth [see Warnings and Precautions (5.12), Postmarketing Experience (6.2), Information for Patients (17), and the Medication Guide].
A BELBUCA film, if chewed or swallowed, may result in lower peak concentrations and lower bioavailability than when used as directed.
Demonstrate proper administration technique to the patient [see Patient Counseling Information (17)].
