Belbuca

— THERAPEUTIC CATEGORIES —
  • Narcotic analgesics

Belbuca Generic Name & Formulations

General Description

Buprenorphine 75mcg, 150mcg, 300mcg, 450mcg, 600mcg, 750mcg, 900mcg; buccal films; peppermint flavor.

Pharmacological Class

Opioid (partial agonist-antagonist).

How Supplied

Films—60

Generic Availability

NO

Mechanism of Action

Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. The principal action of therapeutic value of buprenorphine is analgesia and is thought to be due to buprenorphine binding with high affinity to opioid receptors on neurons in the brain and spinal cord.

Belbuca Indications

Indications

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

Due to risks of addiction, abuse, and misuse with opioids (can occur at any dosage or duration); increased risks of overdose and death with extended-release/long-acting opioid formulations, reserve for use in patients for whom alternative treatment options are ineffective, not tolerated, or inadequate to provide analgesia. Not indicated as an as-needed (prn) analgesic.

Belbuca Dosage and Administration

Adult

Use lowest effective dose for shortest duration. Apply against inside of cheek; do not chew or swallow. Avoid food or drinks until film dissolves. Rinse teeth/gums with water after film dissolves, and swallow. Individualize. Opioid-naive or opioid non-tolerant: initially 75mcg once daily or every 12hrs (if tolerated) for at least 4 days, then increase to 150mcg every 12hrs. Titrate in increments of 150mcg every 12hrs no sooner than every 4 days. Max 900mcg every 12hrs; consider alternate analgesic if inadequate. Conversion from other opioids: see full labeling. Use 600mcg, 750mcg, and 900mcg doses only following titration from lower doses of Belbuca. Severe hepatic impairment or oral mucositis: reduce initial and titration doses by ½. Concomitant use or discontinuation of CYP3A4 inhibitors or inducers: monitor closely and consider dose adjustments (see full labeling). Withdraw gradually (esp. if opioid-dependent), taper by ≤10–25% every 2–4 weeks.

Children

Not established.

Administration

Wait at least 1hr before brushing teeth.

Belbuca Contraindications

Contraindications

Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Known or suspected GI obstruction, including paralytic ileus.

Belbuca Boxed Warnings

Boxed Warning

Serious and life-threatening risks from use of Belbuca: Addiction, abuse, and misuse; Life-threatening respiratory depression; Accidental exposure; Risks from concomitant use with benzodiazepines or other CNS depressants; Neonatal opioid withdrawal syndrome; Opioid analgesic risk evaluation and mitigation strategy (REMS).

Belbuca Warnings/Precautions

Warnings/Precautions

Assess the potential need for access to naloxone when initiating and renewing therapy. Consider prescribing naloxone based on risk factors for overdose (eg, history of opioid use disorder, prior opioid overdose, household members or other close contacts at risk for accidental ingestion or overdose). Abuse potential (monitor). Life-threatening respiratory depression esp. during initiation or following dose increases. Accidental exposure may cause fatal overdose (esp. in children). Opioid-induced hyperalgesia (OIH) and allodynia; consider dose reduction of current opioid or opioid rotation if OIH is suspected. Sleep-related breathing disorders (including central sleep apnea (CSA), sleep-related hypoxemia); consider dose reduction if CSA develops. COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; monitor and consider non-opioid analgesics. Adrenal insufficiency. Monitor for signs of hypotension when initiating or titrating dose. Head injury. Increased intracranial pressure, brain tumors; monitor. Seizure disorders. CNS depression. Impaired consciousness, coma, shock; avoid. Biliary tract disease. Acute pancreatitis. Oral mucositis: use lower dose; monitor for toxicity. Drug abusers. Moderate or severe hepatic impairment. Hepatotoxicity: obtain baseline LFTs in at-risk patients and monitor during treatment. Risk of QT prolongation (esp. in those with hypokalemia, bradycardia, recent conversion from atrial fibrillation, CHF, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, severe hypomagnesemia). Advise patients to obtain regular dental checkups during treatment. Reevaluate periodically. Avoid abrupt cessation. Elderly. Cachectic. Debilitated. Pregnancy; potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.

REMS

YES

Belbuca Pharmacokinetics

Absorption

Absolute bioavailability: 46–65%.

Systemic exposure was reduced by 23–27% by the ingestion of liquids (cold, hot, and room temperature water) during film administration; coadministraiton with low pH liquid (eg, decaffeinated cola) reduced exposure by ~37%.

Distribution

Plasma protein bound: ~96%.

Metabolism

N-dealkylation (CYP3A4), glucuronidation. 

Elimination

Fecal (69%), renal (30%). Half-life: 27.6 ± 11.2 hours.

Belbuca Interactions

Interactions

Increased risk of hypotension, respiratory depression, sedation with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, general anesthetics, phenothiazines, tranquilizers, muscle relaxants, antipsychotics, alcohol, other opioids); reserve concomitant use in those for whom alternative options are inadequate; limit dosages/durations to minimum required; monitor closely; consider prescribing naloxone if concomitant use is warranted. Avoid concomitant Class 1A (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmics (eg, sotalol, amiodarone, dofetilide). During or within 14 days of MAOIs: not recommended. Risk of serotonin syndrome with serotonergic drugs (eg, SSRIs, SNRIs, TCAs, triptans, 5-HT3 antagonists, mirtazapine, trazodone, tramadol, cyclobenzaprine, metaxalone, MAOIs, linezolid, IV methylene blue); monitor and discontinue if suspected. Avoid concomitant mixed agonist/antagonist and partial agonist opioids (eg, butorphanol, nalbuphine, pentazocine); may reduce effects and/or precipitate withdrawal symptoms. Potentiated by CYP3A4 inhibitors (eg, macrolides, azole antifungals, protease inhibitors). Antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin). May antagonize diuretics; monitor. Paralytic ileus may occur with anticholinergics. Concomitant NNRTIs (eg, efavirenz, nevirapine, etravirine, delavirdine) or PIs (eg, atazanavir, ritonavir); monitor and adjust buprenorphine dose, if needed.

Belbuca Adverse Reactions

Adverse Reactions

Nausea, constipation, headache, vomiting, dizziness, somnolence; respiratory depression, orthostatic hypotension, syncope, hypersensitivity reactions, dental adverse events (eg, tooth fracture, tooth loss), OIH and allodynia.

Belbuca Clinical Trials

See Literature

Belbuca Note

Not Applicable

Belbuca Patient Counseling

See Literature

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