Carfentanil Signals Alert | Millennium Health

Millennium Health Signals Alert™

Carfentanil Extends Deadly Reach in Year Following Reemergence

Published September 2024

Urine drug testing (UDT) data show carfentanil detections grew from 2023-2024 nationally, are geographically widespread, and associated with high rates of polysubstance use

Carfentanil is a fentanyl analogue 100× more potent than fentanyl that was associated with a dramatic spike in overdose deaths in 2016-2017.^1,2
Here we extend our previous analyses^3,4 to show the frequency and geographical distribution of carfentanil detection in fentanyl-positive UDT specimens nationally from August 2019 through June 2024 and compare rates of polysubstance use based on carfentanil detection status.
Carfentanil was detected 277 times nationally between August 2019 and July 2020. It then virtually disappeared from our database for nearly three years, only being detected 11 times in total across the U.S. from August 2020 through June 2023 (Top Left Figure).
Carfentanil reemerged, appearing more consistently in mid 2023; it was detected 134 times from July 2023 through June 2024 (Top Left Figure).
Carfentanil was detected in 21 states between July 2023 and June 2024 (Top Right Figure) compared to 9 states (AK, FL, IL, KY, LA, OH, RI, WA, WI) between August 2019 and July 2020 and 6 states (GA, KY, LA, OH, PA, NY) between August 2020 and June 2023.
Polysubstance use rates were higher among those positive for carfentanil for each drug shown (Bottom Figure); many of which can result from the illicit manufacture of fentanyl or are directly added to illicit supplies of fentanyl and other drugs.⁵
Carfentanil’s reemergence has prompted warnings from health officials recently^6-11 because it may contribute to overdose outbreaks and complicate treatment efforts.^2,12 Given these rapidly evolving trends, we are monitoring carfentanil closely and will provide timely updates to raise awareness of its presence in our communities.

National Frequency and Geographical Distribution of Carfentanil Detection in Fentanyl-Positive Specimens

National Carfentanil Detection Rate and Frequency

(August 2019 – June 2024)

Carfentanil Detection by State

(July 2023 – June 2024)

Drug Detection in Fentanyl-Positive Specimens With and Without Carfentanil (July 2023 – June 2024)

TOP LEFT: National, weekly carfentanil detection rate (%, gray bars) and the four-week, rolling average carfentanil detection rate (blue line) in fentanyl-positive specimens collected between August 1, 2019 and June 30, 2024.

TOP RIGHT: Geographical distribution of carfentanil detection in fentanyl-positive specimens by state between July 1, 2023 and June 30, 2024.

BOTTOM: Detection rate (%) for additional drugs (i.e., polysubstance use rates) in fentanyl-positive specimens stratified by carfentanil detection status. Only specimens with valid/ordered test results for all 10 drugs/drug categories were included for analysis. Novel Illicit Benzodiazepines includes 8-aminoclonazolam, etizolam, flualprazolam, and flubromazolam. Novel Illicit Opioids includes 2-methyl-AP-237, brorphine, and metonitazine.

Note: All analyses were performed on specimens positive for fentanyl. Specimens collected within 30 days of a previous specimen for any given patient were removed to help identify positive results that are more likely to represent unique instances of carfentanil use or exposure.

Methods

Sample Population

This cross-sectional analysis evaluated 158,668 definitive urine drug testing (UDT) results derived from testing performed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on patient specimens from across the U.S. and multiple health care specialties. The LC-MS/MS testing method is a laboratory-developed test with performance characteristics determined by Millennium Health, San Diego, California, which is certified by the Clinical Laboratory Improvement Amendments and accredited by the College of American Pathologists for high-complexity testing. Specimens were collected between August 1, 2019 and June 30, 2024 from patients aged 18 years or older. All specimens had positive UDT results for fentanyl. Specimens collected within 30 days of a previous specimen for any given patient were removed to help identify positive results that are more likely to represent unique instances of carfentanil use or exposure.

The following drugs and drug categories were tested for in patient specimens (all analytes tested are in parentheses): fentanyl (fentanyl, norfentanyl), carfentanil (carfentanil), parafluorofentanyl (parafluorofentanyl), acetylfentanyl (acetylfentanyl, acetylnorfentanyl), acrylfentanyl (acrylfentanyl), heroin (6-monoacetylmorphine [6-MAM], morphine), tramadol (N-desmethyl-tramadol, O-desmethyl-tramadol, tramadol), novel illicit opioids (2-methyl-AP-237, brorphine, metonitazene), novel illicit benzodiazepines (8-aminoclonazolam, etizolam, alpha-hydroxyetizolam, flualprazolam, flubromazolam), xylazine (xylazine, 4-OH-xylazine), methamphetamine (methamphetamine) and cocaine (benzoylecgonine). If any parent drug or metabolite for a given drug/drug category was ordered and detected, the result for that drug/drug category was considered positive. Fentanyl analogues, including carfentanil, are only evaluated if a specimen tests positive for fentanyl. Note that morphine is both a metabolite of heroin and an individual drug, which may lead to an overestimation of heroin positivity. We examined analyte results consistent with either illicit or non-medical drug use; specimens with reported prescriptions for any of the UDT drug categories above were excluded from analysis.

Statistical Methods

The weekly, national carfentanil positivity rate (i.e., number of carfentanil-positive specimens/total number of fentanyl-positive specimens x 100) was analyzed and specimens collected during the first 12-month period (August 2019 – July 2020) and last 12-month period (July 2023 – June 2024) were compared to better understand changes in carfentanil positivity and geographical distribution over time. State-level carfentanil detection was evaluated across the analyzed period and represented visually for the July 2023 – June 2024 time period. Polysubstance use was evaluated during the last 12-month period (July 2023 -June 2024) by comparing positivity rates for 10 drugs/drug categories between specimens that were or were not positive for carfentanil. Positivity rates with 95% confidence interval (CI) values that did not overlap were considered statistically significant.

References

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