Risky Fentanyl ‘Candy’ Drugs Finally Discontinued in the United States

In September 2024 the Food and Drug Administration (FDA) announced that all approved transmucosal immediate-release formulations of the opioid analgesic (painkiller) fentanyl (hereafter, transmucosal fentanyl) would be removed from the U.S. market by the end of the month.[1] Common examples of these drugs are ACTIQ and its generics,[2] which are sweetened lozenges on a stick that are often called fentanyl “lollipops.”

Although the withdrawal of these opioids is welcome news, the FDA never should have approved them in the first place because they contributed to the U.S. opioid epidemic.

About fentanyl

Classified as a Schedule II controlled substance, fentanyl is a synthetic opioid that is considered one of the most potent and fastest-acting opioids ever developed;[3] it is up to 50 times stronger than heroin and 100 times stronger than morphine.[4]

There are two types of fentanyl: pharmaceutical fentanyl and illicitly made fentanyl. In 2022 fentanyl (primarily illicit versions) was involved in most U.S. overdose-related deaths.[5]

In 1993 the FDA approved the first candy form of fentanyl (ORALET) for use alongside anesthesia in children and adults. As early as 1989, Public Citizen’s Health Research Group urged the FDA to stop the clinical trials of Oralet in children due to its potential for abuse and risk of respiratory depression (slowed breathing, which can be deadly).[6] Oralet was eventually discontinued because it was not a commercial success.

In 1998 the FDA approved the transmucosal fentanyl formulation Actiq. Subsequently the agency approved similar formulations, such as ABSTRAL, FENTORA and generics (tablets that dissolve in the mouth), LAZANDA (a nasal spray), ONSOLIS (a small film that is placed in the mouth) and SUBSYS and generics (sprays that go under the tongue).

The FDA has limited the approved uses of transmucosal fentanyl drugs to treating breakthrough pain (bouts of sudden pain that are not relieved by a patient’s usual pain-management plan) in cancer patients who are already receiving and are tolerant to around-the-clock opioid therapy to manage their persistent cancer pain.[7] This restriction was imposed because the risk of life-threatening respiratory depression is highest in patients who are not opioid tolerant (meaning they have not gotten used to lower doses of such drugs).

Other currently available pharmaceutical formulations of fentanyl include injectable generics (approved for use in anesthesia only)[8] and generic skin patches (approved for consistent, severe pain in opioid-tolerant patients who require an extended treatment period with a daily analgesic and for whom alternative treatment options are inadequate).[9]

The downfall of candy fentanyl

In its September 2024 announcement, the FDA noted that it did not request the removal of transmucosal fentanyl products.[10] Instead these drugs will be voluntarily withdrawn by their manufacturers, including BioDelivery Sciences International, Teva Pharmaceuticals and West Therapeutic Development. The Federal Register indicates that these products were not discontinued or withdrawn for effectiveness or safety reasons.

For decades, however, drugmakers have promoted transmucosal fentanyl products for unapproved uses. For example, in 2008 Cephalon (the former manufacturer of Actiq) entered a criminal plea with the Department of Justice to resolve allegations that it promoted the drug illegally for use in patients who were not opioid tolerant and those with noncancer pain (including those with migraine and sickle cell pain crisis).[11]

In 2011 the FDA established a risk evaluation and mitigation strategy (REMS), involving all drugmakers and pharmacies dispensing transmucosal fentanyl, to attempt to limit the availability of these drugs to approved uses and to mitigate the associated risks (including abuse, addiction, misuse and overdose).[12] In 2020 the FDA tightened the REMS program (including by requiring participating prescribers and pharmacies to document a patient’s opioid tolerance level with each prescription). The tightening was in response to data showing that transmucosal fentanyl continued to be taken by patients who were not opioid tolerant.[13]

However, the lawsuits continued against opioid makers. For example, in 2022 Teva (then the manufacturer of Actiq and Fentora as well as other generic opioids) agreed to pay $4.2 billion over 13 years to settle nationwide allegations that it had marketed its opioid products, including transmucosal fentanyl, illegally and did not maintain effective diversion controls.[14]

As of September 2024 fewer than 150 patients were enrolled in the REMS program for transmucosal fentanyl, according to the FDA. The low enrollment suggests that the voluntary decision to discontinue these products was driven by decreased sales (in contrast, in 2006 the sales of Actiq alone exceeded $590 million).[15]

What You Can Do

Do not use fentanyl unless you are a cancer patient with breakthrough cancer-related pain, are considered opioid tolerant, and are under the care of an experienced clinician.

Call 911 immediately in case of an opioid overdose or accidental exposure. Signs and symptoms of dangerous overdose include constricted pupils, decreased level of consciousness, lack of response to stimulation, and slowed breathing.[16]

If you take any opioids or are the caregiver of someone who does, keep over-the-counter naloxone nasal sprays (NARCAN, RIVIVE and generics) readily available to reverse the effects of overdose. Naloxone also is available as prescription nasal sprays (KLOXXADO, REXTOVY, REZENOPY) and as an injectable (ZIMHI).[17]
 

References

[1] Food and Drug Administration. Update: Questions and answers: FDA approves a class Risk Evaluation and Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl (TIRF). September 16, 2024. https://www.fda.gov/drugs/information-drug-class/questions-and-answers-fda-approves-class-risk-evaluation-and-mitigation-strategy-rems-transmucosal. Accessed January 6, 2025.

[2] Teva Pharmaceuticals. Label: fentanyl (ACTIQ). December 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020747s062lbl.pdf. Accessed January 3, 2025.

[3] Thumma A, Mfoafo K, Babanejad N, et al. Abuse potential of fentanyl and fentanyl analogues. Bioimpacts. 2024;14(6):27691.

[4] Centers for Disease Control and Prevention. The facts about fentanyl. https://www.cdc.gov/overdose-resources/pdf/CDC_Fentanyl-Fact-Sheet_General_508.pdf. Accessed January 6, 2025.

[5] Centers for Disease Control and Prevention. Overdose prevention. Fentanyl. October 30, 2024. https://www.cdc.gov/overdose-prevention/about/fentanyl.html. Accessed January 6, 2025.

[6] Public Citizen. Letter to the FDA regarding fentanyl (ORALET) narcotic lollipop. February 22, 1989. https://www.citizen.org/wp-content/uploads/1157.pdf. Accessed January 6, 2025.

[7] Food and Drug Administration. Update: Questions and answers: FDA approves a class Risk Evaluation and Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl (TIRF). September 16, 2024. https://www.fda.gov/drugs/information-drug-class/questions-and-answers-fda-approves-class-risk-evaluation-and-mitigation-strategy-rems-transmucosal. Accessed January 6, 2025.

[8] Rising Pharma. Label: fentanyl injectable (generics only). December 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/016619s054lbl.pdf. Accessed January 6, 2025.

[9] SpecGx LLC. Label: fentanyl transdermal (generics only). May 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/016619s054lbl.pdf. Accessed January 6, 2025.

[10] Food and Drug Administration. Update: Questions and answers: FDA approves a class Risk Evaluation and Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl (TIRF). September 16, 2024. https://www.fda.gov/drugs/information-drug-class/questions-and-answers-fda-approves-class-risk-evaluation-and-mitigation-strategy-rems-transmucosal. Accessed January 6, 2025.

[11] Department of Justice. Biopharmaceutical company, cephalon, to pay $425 million & enter plea to resolve allegations of off-label marketing. September 29, 2008. https://www.justice.gov/archive/opa/pr/2008/September/08-civ-860.html. Accessed January 6, 2025.

[12] Stanley TH. The fentanyl story. J Pain. 2014;15(12):1215-1226.

[13] Food and Drug Administration. Statement. FDA takes further steps to confront opioid crisis through risk evaluation and mitigation strategy programs. December 23, 2020. https://www.fda.gov/news-events/press-announcements/fda-takes-further-steps-confront-opioid-crisis-through-risk-evaluation-and-mitigation-strategy. Accessed January 6, 2025.

[14] Massachusetts Office of the Attorney General. AG Healey announces $6.6 billion nationwide settlement with Teva and Allergan over claims of illegally marketing opioids. November 23, 2022. https://www.mass.gov/news/ag-healey-announces-66-billion-nationwide-settlement-with-teva-and-allergan-over-claims-of-illegally-marketing-opioids. Accessed January 6, 2025.

[15] New York State Department of Financial Services. Statement of charges and notice of hearing in the matter of Teva, Cephalon and other opioid companies. 2020. https://www.dfs.ny.gov/system/files/documents/2020/08/ea20200818_teva_allergan_stmt_charges_notice_hearing.pdf. Accessed January 6, 2024.

[16] California Department of Public Health. Responding to a fentanyl overdose: What California first responders need to know. January 2022. https://www.cdph.ca.gov/Programs/CCDPHP/sapb/CDPH%20Document%20Library/Responding-to-a-Fentanyl-Overdose.pdf. Accessed January 6, 2025.

[17] Opioid overdose antidotes to avoid: High-dose naloxone and nalmefene nasal sprays. Worst Pills, Best Pills News. September 2024. https://www.worstpills.org/newsletters/view/1618. Accessed January 6, 2025.