FDA WARNS THAT BUPRENORPHINE MEDICATIONS DISSOLVED IN MOUTH INCREASE RISK OF DENTAL PROBLEMS

January 28, 2022

Here’s an important alert for patients using buprenorphine products dissolved in the mouth. Buprenorphine, a partial opioid agonist, is available as a single-ingredient product in multiple forms, including two that are taken by dissolving them in the mouth:

• tablets placed under the tongue for treatment of opioid-use disorder (marketed in multiple generic versions)[2]
• films placed inside the cheek for pain management (sold under the brand name BELBUCA[3] and in one generic version[4])

Buprenorphine is also available in combination products containing the opioid antagonist naloxone for treatment of opioid-use disorder in two forms that are to be taken by dissolving them in the mouth:

• tablets administered under the tongue (marketed under the brand name ZUBSOLV[5] and in multiple generic versions)
• films placed under the tongue or inside the cheek (sold under the brand name SUBOXONE[6] as wells as in multiple generic versions)

On Jan. 12, 2022, the Food and Drug Administration (FDA) warned that dental problems have been reported in patients using buprenorphine-containing tablets and films that are taken by dissolving them in the mouth.[7] These problems have included tooth decay, cavities, oral infections and loss of teeth. The FDA noted that these problems can be serious and have occurred in people with no history of dental issues. The FDA concluded that the benefits of these products for treating opioid-use disorder and pain continue to outweigh their risks.

The FDA alert was based on a review of adverse-event reports submitted to the agency or reported in the medical literature through December 2018. The FDA’s review identified 305 cases of dental adverse events associated with use of buprenorphine medications dissolved in the mouth, with 131 of these adverse events being classified as serious.

The agency noted that although patients with opioid-use disorder are more likely to have poor dental health, 26 of the 305 cases involved severe dental adverse events in patients with no reported prior dental problems. In addition, although most of the adverse-event reports involved patients using buprenorphine for opioid-use disorder, there were 28 patients who experienced severe dental problems while using buprenorphine products approved only for pain management (for example, Belbuca) or who had reported taking buprenorphine for pain.

The average age of the patients for the 305 cases reviewed by the FDA was 42 years (range 18-71 years). For some cases, the dental problems occurred as soon as two weeks after beginning the buprenorphine treatment, with the median time to diagnosis being about two years after initiating therapy.

Many of the cases reported to the FDA involved a combination of dental decay, tooth loss and tooth fracture in many teeth. Many reports were submitted by health care professionals who documented extensive dental involvement, including, for example, “all upper,” “all lower,” “all,” ”majority,” “most” or “multiple” teeth or “rampant decay.” Some cases mentioned involvement of 11 or more teeth, with 11 cases noting that all teeth were affected. Of the 305 cases, 151 reported treatment for the dental adverse events, with 71 cases requiring tooth extraction or removal. Other treatments included root canal, dental surgery, and dental restoration procedures involving crowns and implants.

Notably, there are other forms of buprenorphine products that are administered by injection or skin patch, but the FDA did not identify concerns about dental adverse events for these other forms of the drug. This suggests the direct exposure of teeth to buprenorphine makes the teeth susceptible to decay and damage.

To address this newly identified risk associated with buprenorphine, the FDA is requiring the addition of a new warning to the product labeling, including to the patient medication guides, for all buprenorphine-containing medications dissolved in the mouth. The new labeling will include strategies for maintaining or improving oral health while using these drugs, including recommendations for prescribers to refer patients to dental care services and encourage them to have regular dental checkups during buprenorphine therapy.

What You Can Do

If you are currently taking a buprenorphine product that is dissolved in the mouth, you should continue taking it as prescribed, particularly if you are using it to treat opioid-use disorder. The benefits of taking such buprenorphine products for treatment of opioid-use disorder outweigh these drugs’ risks, including the risk of dental adverse events. Do not stop taking buprenorphine products that are dissolved in the mouth without first talking to your doctor because suddenly stopping these medications can cause severe withdrawal symptoms or relapse of opioid misuse, which could result in overdose and death.

Before using a buprenorphine medicine that is to be taken by dissolving it in the mouth, inform your health care professional if you have a history of tooth problems, including cavities. You should schedule a dentist visit soon after starting this medication and schedule regular dental checkups as long as you are taking it. You should contact your doctor and dentist immediately if you experience any problems with your teeth or gums.

When using buprenorphine medicine dissolved in the mouth, after a dose of the medicine is completely dissolved, you should take a large sip of water, swish it gently around your teeth and gums, and swallow. You should wait at least one hour before brushing your teeth to avoid damage to your teeth and allow your mouth time to return to its natural state.

If you experience dental adverse effects involving a buprenorphine medication dissolved in the mouth, talk to you doctor about whether you should switch to a different form of buprenorphine, such as a skin-patch version, or change to another drug for treating your opioid-use disorder or pain. You also should report the dental adverse event to the FDA MedWatch program online at https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=consumer.reporting1.

To see the FDA’s safety alert, visit the following link: https://www.fda.gov/media/155352/download.
 

References

[1] Food and Drug Administration. Drug safety communication: FDA warns about dental problems with buprenorphine medicines dissolved in the mouth to treat opioid use disorder and pain. January 12, 2022. https://www.fda.gov/media/155352/download. Accessed January 24, 2022.

[2] Actavis Pharma, Inc. Label: buprenorphine sublingual tablets. August 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=03819118-86f6-4329-adaf-4599e7b71f46&type=display. Accessed January 24, 2022.

[3] BioDelivery Sciences International, Inc. Label: buprenorphine buccal film (BELBUCA). March 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/207932s015lbl.pdf. Accessed January 24, 2022.

[4] Food and Drug Administration. Approval letter for ANDA 211594. August 3, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2021/211594Orig1s000ltr.pdf. Accessed January 24, 2022.

[5] Orexo US, Inc. Label: buprenorphine and naloxone sublingual tablets (ZUBSOLV). March 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204242s019lbl.pdf. Accessed January 24, 2022.

[6] Indivior Inc. Label: buprenorphine and naloxone sublingual film (SUBOXONE). March 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022410s042lbl.pdf. Accessed January 24, 2022.

[7] Food and Drug Administration. Drug safety communication: FDA warns about dental problems with buprenorphine medicines dissolved in the mouth to treat opioid use disorder and pain. January 12, 2022. https://www.fda.gov/media/155352/download. Accessed January 24, 2022.