Eluxadoline Dispensing in Medicare Peaked in 2018, Then Fell as Costs Climbed

Dispensing of eluxadoline, a US Food and Drug Administration-approved therapy for irritable bowel syndrome with diarrhea, rose sharply in Medicare Part D after its 2015 approval, peaked in 2018, and then declined through 2023, according to a retrospective repeated cross-sectional analysis of federal prescribing data published in Drugs – Real World Outcomes.

The dataset contained 7,826 prescriber-year observations corresponding to 3,866 unique prescribers, of whom 1,878 appeared in more than one calendar year. Because the public use files suppress any prescriber-drug record derived from fewer than 11 claims, all figures reflect observable utilization and may underestimate true totals, particularly for low-volume prescribers, smaller specialties, and less populous states. The authors measured utilization primarily in standardized 30-day fills, a metric that converts varying days of supply into comparable fill equivalents, so that a 90-day supply counts as three fills. Total claims served as a secondary measure.

Nationally, standardized 30-day fills climbed from 4,410.9 in 2016 to 17,685.3 in 2017 and peaked at 19,860.2 in 2018 before declining gradually to 15,326.0 in 2023. Total claims followed a similar trajectory, peaking at 18,148 in 2018. The number of unique observable prescribers jumped from 265 in 2016 to 1,029 in 2017, reached a high of 1,192 in 2020, and fell back to 964 by 2023. Mean days supplied per claim remained stable at roughly 30 days throughout the period, indicating that the volume trends were not driven by shifts toward longer or shorter prescriptions.

Spending moved in the opposite direction of volume in the later years. Total drug costs grew from $4.50 million in 2016 to $21.66 million in 2023, and the inflation-adjusted cost per standardized 30-day fill, expressed in 2023 US dollars using the Medical Care component of the Consumer Price Index for All Urban Consumers, rose steadily from $1,021 to $1,414. The authors note that this divergence between falling volume and rising per-fill cost is consistent with documented pricing behavior for branded single-source drugs in Part D, where average net prices of brand-name prescriptions more than doubled between 2010 and 2019. However, the public use files report gross drug cost before manufacturer rebates and discounts, so the mechanism behind eluxadoline’s price trajectory cannot be confirmed from these data.

Geographically, dispensing was markedly uneven. Median state dispensing rates, calculated as standardized 30-day fills per 100,000 Part D utilizers, rose from 7.3 in 2016 to 43.7 in 2018 and then ranged between 27.6 and 35.9 from 2019 through 2023. Averaged across the study period, the highest rates appeared in New Jersey at 102.8 and Connecticut at 81.3 per 100,000, followed by Kentucky, South Dakota, and Missouri. In absolute terms, dispensing was concentrated in a handful of large states: California, Texas, New Jersey, New York, and Florida together accounted for 39.5 percent of all observed fills.

The analysis distinguished between volume and intensity. State Part D utilizer counts correlated strongly with total fills each year, with Spearman rank correlation coefficients between 0.80 and 0.89, meaning larger states naturally contributed more dispensing. In contrast, correlations between utilizer counts and population-adjusted rates were weak, ranging from 0.03 to 0.34, and did not remain statistically significant after multiple-comparison adjustment. Kruskal-Wallis tests comparing dispensing rates across US Census regions produced nominal p-values between 0.009 and 0.223, but no year met the adjusted significance threshold of q below 0.05, with the smallest adjusted value at 0.054. Unweighted mean regional rates were consistently highest in the Northeast and lowest in the West.

Geographic concentration, quantified with Gini coefficients across all 50 states and the District of Columbia, was highest in 2016 at 0.463, dropped to 0.292 in 2017, and settled in a moderate range of 0.307 to 0.352 from 2018 to 2023. Outlier detection using modified Z-scores based on the median absolute deviation flagged New Jersey as a recurrent high-rate outlier in 2016, 2019, and 2021 through 2023, with South Dakota also flagged in 2019. Sensitivity analyses that excluded zero-observable or sparsely observed state-years generally produced lower Gini coefficients, particularly for 2016, and changed some outlier designations: South Dakota was no longer an outlier in 2019, while Connecticut emerged as one in 2023. New Jersey remained a high-rate outlier across all specifications. The authors emphasize that greater concentration does not itself indicate inappropriate prescribing, unequal access, or differences in clinical need.

Prescriber type emerged as a consistent differentiator. Gastroenterologists accounted for the largest share of unique eluxadoline prescribers in every study year, comprising 57.4 percent in 2016 and between 41.5 and 46.6 percent during 2017 through 2023. Primary care clinicians made up 13.2 to 23.4 percent of prescribers, and nurse practitioners 6.8 to 13.0 percent. In negative binomial models of annual claim counts with calendar-year and geographic fixed effects and standard errors clustered at the prescriber level, gastroenterologists showed higher dispensing intensity than primary care clinicians, with an incidence rate ratio of 1.17 and a 95 percent confidence interval of 1.13 to 1.21. Nurse practitioners, physician assistants, internal medicine clinicians, and other prescriber categories each showed modestly higher intensity than primary care as well. The authors caution that these estimates are conditional on prescribers with observable utilization meeting the reporting threshold and do not represent the likelihood of eluxadoline use among all clinicians within each specialty.

The safety context is central to interpreting these patterns. Eluxadoline, a mixed mu-opioid and kappa-opioid receptor agonist and delta-receptor antagonist that reduces gastrointestinal motility and visceral pain signaling, carries important contraindications. Post-marketing surveillance identified rare but serious adverse events including pancreatitis and sphincter of Oddi spasm, with heightened risk among patients without a gallbladder and those who consume alcohol. In 2017, the FDA issued a safety communication warning of increased pancreatitis risk in patients without a gallbladder. The study’s post-2018 decline in dispensing is temporally consistent with a response to that communication, but the authors stress that the data cannot distinguish reduced use in newly contraindicated patients from other explanations, including rising cost, plan-level utilization management, treatment discontinuation due to insufficient benefit or adverse effects, or switching to alternatives such as alosetron, rifaximin, or tricyclic antidepressants.

The authors frame the work as descriptive and hypothesis generating rather than evaluative. The public use files contain aggregate prescriber-drug data without beneficiary-level clinical detail, so indication, contraindications, appropriateness, initiation versus continuation, and clinical outcomes cannot be assessed. State rates were standardized to all Part D utilizers rather than to beneficiaries with IBS-D, so differences may reflect disease prevalence, age structure, contraindication prevalence, and specialist supply in addition to dispensing practices. The analysis also excludes dispensing outside Part D, such as commercial insurance or cash-paid use, and prescriber state may not reflect beneficiary residence. Because irritable bowel syndrome frequently affects younger and middle-aged adults, Part D captures only a subset of US eluxadoline utilization, and international generalizability is limited since the European Union marketing authorization was withdrawn in December 2020 at the manufacturer’s request. The authors call for beneficiary-level studies to evaluate how much observed variation reflects case mix, contraindication prevalence such as prior cholecystectomy, and plan coverage, and whether utilization patterns are associated with safety outcomes such as pancreatitis-related hospitalization.

Subject of Research: National and state-level trends in eluxadoline dispensing and spending in Medicare Part D from 2016 to 2023

Article Title: Eluxadoline Utilization in Medicare Part D, 2016–23: National Trends, Geographic Variation, Prescriber-Type Patterns, and Spending

Article References: Hammersmith, A. R., Yunusa, I., Cai, C., & Love, B. L. (2026). Eluxadoline Utilization in Medicare Part D, 2016–23: National Trends, Geographic Variation, Prescriber-Type Patterns, and Spending. Drugs – Real World Outcomes. https://doi.org/10.1007/s40801-026-00587-1

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00587-1

Keywords: eluxadoline, Medicare Part D, irritable bowel syndrome with diarrhea, pharmacoepidemiology, geographic variation, prescriber specialty, gastroenterology, drug spending, CMS public use files, drug safety, health services research, older adults