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Fentanyl-based OUD guidance needed in light of crisis
Roger Selvage 1990

Fentanyl-based OUD guidance needed in light of crisis

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Loren Bonner

The latest CDC data find that deaths involving synthetic opioids like fentanyl increased by a staggering 80% over the past 2 years. These drugs were involved in more than two-thirds of the overdose deaths in the year ending March 2022. But fentanyl isn’t just causing fatal overdoses; it’s also making it harder for patients to start treatment for opioid use disorder (OUD).

Due to its potency and increased prevalence of misuse, fentanyl has presented challenges in starting patients on medications for opioid use disorder (MOUD) like buprenorphine.

“Patients started on buprenorphine following fentanyl use often experience significant precipitated withdrawal, which can lead the patient to not continue the buprenorphine or to return to fentanyl use,” said Sarah Melton, PharmD, a professor of pharmacy practice at the Gatton College of Pharmacy at East Tennessee State University. “Because the precipitated withdrawal felt so horrible, many patients will refuse to ever try buprenorphine again.”

Individuals with fentanyl OUD are at higher risk of overdose and death, creating an urgent situation that warrants evaluation of improved treatment approaches in addition to expanding and improving access to evidence-based care.

“Guidance is needed as the overdose rates are skyrocketing from fentanyl and fentanyl-analogues,” said Melton. “Traditional treatment with methadone and buprenorphine is not as straightforward as with prescription opioids such as oxycodone or morphine.” She said it’s paramount that fentanyl-based OUD guidance for prescribers and pharmacists be published and distributed.

In late 2022, Congress passed the Mainstreaming Addiction Treatment Act, which would eliminate DEA’s “X-waiver.” Melton said more health care professionals will be able to prescribe buprenorphine for OUD with limited training now that this requirement is removed.

Microdosing protocol

“Fentanyl has a distinct pharmacological profile compared with other opioids that contributes to this high risk of precipitated withdrawal from buprenorphine administration,” said Melton, who also practices as a clinical pharmacist at a community health center.

Fentanyl is 100 times more potent than morphine and has a gradual release from lipid tissue, which increases the half-life.

“When patients refuse to continue to take buprenorphine because of a severe precipitated withdrawal, it is considered a ‘failed induction,’ ” said Melton.

In order to treat patients who use fentanyl—and in the absence of sufficient research, data, and guidance—many clinicians have begun using microdosing approaches.

In a microdosing protocol, the patient receives a low dose of buprenorphine, which is gradually increased over several days to the target dose. A patient can continue to take a full dose of fentanyl until the therapeutic dose of buprenorphine has been achieved. At that point, the full opioid agonist or fentanyl is discontinued.

Melton said the microdosing process usually takes 3 to 10 days to work. According to the theory behind the approach, gradually adding buprenorphine on to the μ receptors using very small doses that are escalated daily will avoid displacement of the full agonist all at once, which is what triggers precipitated withdrawal, said Melton. “There are many proposed microdosing regimens that are being used in clinical practice and the literature does not support one over another,” she said.

While the research is continuing to evaluate the best way to prevent precipitated withdrawal in patients who are using high potency fentanyl, the approach has helped clinicians treat patients during this time.

Melton recommends all interested health care professionals become familiar with Providers Clinical Support System ( and review education about treatment of OUD, especially education on microdosing of buprenorphine for those using fentanyl.


For patients seeking treatment for OUD, stigma continues to be an issue.

“Pharmacists need to be on the front line to fight stigma by stocking buprenorphine in their pharmacies, being willing to dispense it, educating patients about and providing fentanyl test strips, providing naloxone, and collaborating with prescribers to ensure patients are getting comprehensive substance use treatment,” said Melton.

She said stigma will only worsen as the prevalence of fentanyl, combined with the drug xylazine, spreads across the United States.

Individuals who use these drugs in combination present with severe ulcers and wounds when injected, and the combination is increasing the severity of substance use disorders and making treatment more difficult, according to Melton. ■

APhA–APPM’s Pain, Palliative Care and Addiction Special Interest Group offers a resource for pharmacists that is designed to provide evidence-based information addressing misconceptions surrounding OUD and MOUD and reduce stigma available at:



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