Pharmacy Times, March 2016 Central Nervous System, Volume 82, Issue 3

The FDA has approved Belbuca buccal film for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

The FDA has approved Belbuca (buprenorphine; Endo Pharmaceuticals) buccal film for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The approval carries the limitations that because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with long-acting opioid formulations, the use of Belbuca should be reserved for patients in whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient pain management. The limitation also states that Belbuca is not indicated as an as-needed analgesic.1 Belbuca uses a dissolving film that is absorbed through the inner lining of the cheek, and it is the first and only buprenorphine product to be administered this way.2 Belbuca is a Schedule III controlled substance.1

Pharmacology and Pharmacokinetics

Belbuca is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. Its mean plasma elimination halflife is approximately 27 hours.1

Dosage and Administration

Belbuca should only be prescribed by providers who are knowledgeable in the use of potent opioid medications for chronic pain management. Opioid-naïve patients should begin treatment with 75 mcg Belbuca once daily or every 12 hours, as tolerated, for at least 4 days before increasing the dose to 150 mcg every 12 hours. Patients currently using other opioid medications should be tapered to a daily opioid dose of 30 mg or less of oral morphine sulfate—equivalents before converting to treatment with Belbuca.

Belbuca should not be abruptly discontinued in a physically dependent patient. Patients with severe hepatic impairment or oral mucositis should receive half the starting and incremental doses.1

Clinical Trials

The FDA approval was based on data from two 12-week, double-blind, randomized, placebo-controlled trials in patients with moderate to severe chronic lowback pain. One study consisted of opioidexperienced patients, and the other consisted of opioid-naïve patients. In both trials, patients were titrated to a tolerated, effective dose of Belbuca and then randomized to receive either continuation of Belbuca or placebo. Both trials demonstrated a consistent, statistically significant improvement in patientreported pain relief in the Belbuca group compared with the placebo group.2

Contraindications, Warnings, and Precautions

Belbuca carries a boxed warning regarding its potential to lead to addiction, abuse, misuse, lifethreatening respiratory depression, and accidental exposure, especially in children. The boxed warning also states that prolonged use of Belbuca during pregnancy can result in neonatal opioid withdrawal syndrome.

Treatment with Belbuca is contraindicated in patients with significant respiratory depression, acute or severe asthma, known or suspected gastrointestinal obstruction (including paralytic ileus), and hypersensitivity to buprenorphine. Elderly, cachectic, debilitated patients and patients with chronic pulmonary disease are more likely to develop life-threatening respiratory depression and should be monitored closely. Some patients using Belbuca experienced a prolonged QTc interval. Severe hypotension may also occur during treatment. Patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness should be monitored closely for sedation and respiratory depression. The use of Belbuca should also be avoided in patients with impaired consciousness or coma.

Because Belbuca may cause fetal harm, it should not be used in patients who are breast-feeding. Patients with moderate or severe hepatic impairment who are using Belbuca should be monitored for signs and symptoms of toxicity or overdose.

Concomitant use of Belbuca with central nervous system depressants may result in profound sedation, respiratory depression, and death. Use of Belbuca with benzodiazepines may increase buprenorphineinduced respiratory depression. An increase in buprenorphine plasma concentrations may occur with the initiation of CYP3A4 inhibitors or the discontinuation of CYP3A4 inducers. The combination of Belbuca and mixed agonist/antagonist and partial agonist opioid analgesics should be avoided, as this may result in a reduction of analgesic effect or a precipitation of withdrawal symptoms.

The most common adverse reactions (>5%) were nausea, constipation, headache, vomiting, dizziness, and somnolence.1

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.


  • Belbuca [prescribing information]. Malvern, PA: Endo Pharmaceuticals; 2015.
  • US FDA approves Belbuca (buprenorphine) buccal film for chronic pain management [press release]. Dublin, Ireland, and Raleigh, NC: Endo Pharmaceuticals; October 26, 2015. Accessed December 2015.