Responding to advocacy by the AMA and other medical organizations, the Food and Drug Administration (FDA) has clarified that buprenorphine labeling does not require a maximum-dose restriction and that dosage decisions should be made on an individualized basis. The AMA is urging all payers and states to remove policies that include a maximum dose restriction.
For many buprenorphine products used to treat opioid-use disorder, FDA labels have downplayed the effectiveness of daily doses above 24 mg. The AMA has pointed out that these labels are old and don’t reflect current use of illicitly manufactured and highly potent fentanyl, which accounted for 70% of all overdose deaths in 2022.
The agency is now recommending that higher doses of buprenorphine are suitable, when warranted, to treat certain cases of substance-use disorder.
Dosing can be tailored
Late last year, the FDA issued a Federal Register notice stating that current “labeling for [buprenorphine] products may be misinterpreted by some as establishing a maximum dosage when none exists.” The concern is misinterpretation of these labeling statements may be affecting patient access to medication.
The notice provided updated FDA-recommended language. “After treatment induction to the recommended dose of [equivalent 16 mg buprenorphine OR equivalent 16 mg/4 mg buprenorphine/naloxone] per day, dosing should be further adjusted based on the individual patient and clinical response,” the agency clarified.
Daily doses higher than 24 mg buprenorphine or equivalent to 24 mg/6 mg buprenorphine/naloxone “have not been investigated in randomized clinical trials but may be appropriate for some patients,” the FDA said.
The notice also accounted for use of buprenorphine during pregnancy, stating that “dosage adjustments of buprenorphine, such as using higher doses, may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy.”
The agency is encouraging manufacturers of supplemental new drug applications to modify labeling statements for buprenorphine-containing products for the treatment of opioid-use disorders.
Why higher doses can help
AMA policy recommends that patients should be able to receive doses exceeding FDA-approved limits when clinically recommended by their prescriber.
Bolstering the AMA’s stance, recent research published in JAMA® found an association between higher doses of buprenorphine and lower rates of subsequent behavioral health-related emergency department and inpatient-care visits. Specifically, patients taking more than 16–24 mg of buprenorphine daily took 20% longer than those taking between 8–16 mg of buprenorphine to seek ED or inpatient health care related to behavioral health within the first year after receiving treatment.
Those taking daily doses exceeding 24 mg of buprenorphine went 50% longer before needing care, compared to those taking 8–16 mg a day.
“Policymakers must take note of these findings and the growing body of evidence that further affirm buprenorphine as a safe, effective and lifesaving tool in the fight against the illicit fentanyl overdose epidemic,” Bobby Mukkamala, MD, said when the analysis was released last fall. Dr. Mukkamala is the AMA’s president-elect and chair of the AMA Substance Use and Pain Care Task Force.
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Payers have restricted buprenorphine
It’s also critical that health insurance companies, Medicaid and Medicare remove dosage caps for buprenorphine, Dr. Mukkamala added.
The AMA has received multiple reports from physicians that health insurers have been using current FDA labeling to impose restrictions such as prior authorization, quantity limits, or outright denials on daily doses of 24 mg or higher of buprenorphine. These restrictions often prevent patients from accessing buprenorphine at a dose that can effectively manage their opioid-use disorder, which can have tragic results. Several states also have statutory buprenorphine dose restrictions based on the outdated FDA labeling.
The AMA has urged that outdated policies be revised to ensure patients with opioid-use disorder can access lifesaving, evidence-based care. In its 2024 report on the drug-related overdose and death epidemic, the AMA recommended the removal of harmful, one-size-fits-all restrictions on opioid therapy that contradict policies from Centers for Disease Control and Prevention and the Federation of State Medical Boards. Also, in recent comments on 2026 Medicare Advantage and Part D proposals, the AMA urged that prior authorization and quantity limits on buprenorphine be prohibited in these programs.
The AMA believes that science, evidence and compassion must continue to guide patient care and policy change as the nation’s opioid epidemic evolves into a more dangerous and complicated illicit drug overdose epidemic. Learn more at the AMA’s End the Epidemic website.
