Effect of Mild or Moderate Hepatic Impairment on the Pharmacokinetics of Avacopan, a Small-Molecule Complement C5a Receptor Antagonist, for the Treatment of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Avacopan is currently approved in several regions of the world as an oral treatment in combination with standard therapy, including glucocorticoids, for adult patients with severe active antineutrophil cytoplasmic autoantibody-associated vasculitis. In vitro and clinical studies have established that avacopan is primarily eliminated through cytochrome P450 3A4 metabolism. This Phase 1, open-label, single-dose study (ClinicalTrials.gov identifier: NCT06004934) was conducted to evaluate the effect of mild (n = 8) or moderate (n = 8) hepatic impairment compared with normal hepatic function (n = 8) on the pharmacokinetics, safety, and tolerability of a single oral dose of 30 mg of avacopan in patients without active antineutrophil cytoplasmic autoantibody-associated vasculitis. Relative to participants with normal hepatic function, in participants with mild or moderate hepatic impairment, the avacopan area under the plasma concentration-time curve from time 0 to infinity geometric mean ratios (90% confidence intervals) were 1.3 (0.9-2.0) and 1.1 (0.6-2.0), respectively, and the avacopan maximum plasma concentration geometric mean ratios (90% CIs) were 1.0 (0.8-1.3) and 0.8 (0.6-1.1), respectively. The geometric mean ratios of metabolite M1 also revealed no pharmacokinetically relevant increase in the peak exposure of M1 in participants with mild or moderate hepatic impairment. Thus, no avacopan dosage adjustment is necessary for patients with mild or moderate hepatic impairment.

Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic.

OBJECTIVES: Opioid use disorder (OUD) is a major public health concern in the USA, resulting in high rates of overdose and other negative outcomes. Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analysed the distribution of methadone for the treatment of OUD across the USA over the past decade and through the COVID-19 pandemic. DESIGN: Retrospective observational study using secondary data analysis of the Drug Enforcement Administration and Medicaid Databases. SETTING: USA. PARTICIPANTS: Patients who were dispensed methadone at US opioid treatment programmes (OTPs). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the overall pattern in methadone distribution and the number of OTPs in the USA per year. The secondary outcome was Medicaid prescriptions for methadone. RESULTS: Methadone distribution for OUD has expanded significantly over the past decade, with an average state increase of +96.96% from 2010 to 2020. There was a significant increase in overall distribution of methadone to OTP from 2010 to 2020 (+61.00%, p<0.001) and from 2015 to 2020 (+26.22%, p<0.001). However, the distribution to OTPs did not significantly change from 2019 to 2021 (-5.15%, p=0.491). There was considerable state-level variation in methadone prescribing to Medicaid patients with four states having no prescriptions. CONCLUSIONS: There have been dynamic changes in methadone distribution for OUD. Furthermore, pronounced variation in methadone distribution among states was observed, with some states having no OTPs or Medicaid coverage. New policies are urgently needed to increase access to methadone treatment, address the opioid epidemic in the USA and reduce overdose deaths.

Pronounced Regional Disparities in United States Methadone Distribution.

BACKGROUND: Methadone is an evidence-based treatment for opioid use disorder (OUD) and pain management. Methadone for OUD may be difficult for some patients to access, particularly those in rural areas. OBJECTIVE: The purpose of this study was to characterize methadone distribution patterns between 2017 and 2019 across the United States. METHODS: The US Drug Enforcement Administration's Automated Reports and Consolidated Ordering System was used to acquire the number of opioid treatment programs (OTPs) per state and methadone distribution weight in grams. Methadone distributions by weight, corrected for state population and number of OTPs, were compared from 2017 to 2019 between states, within regions, and nationally. RESULTS: The national distribution of methadone increased +12.3% for OTPs but decreased -34.6% for pain. Whereas all states saw a decrease in pain distribution, the Northeast showed a significantly smaller decrease than all other regions. Additionally, the majority of states experienced an increase in distribution for OTPs, and most states demonstrated a relatively stable or increasing number of OTPs, with an +11.5% increase nationally. The number of OTPs per 100K state population ranged from 2.1 in Rhode Island to 0.0 in Wyoming. CONCLUSION AND RELEVANCE: Although methadone distribution for OUD was increasing in the United States, the pronounced regional disparities identified warrant further consideration to improve patient access to this evidence-based pharmacotherapy, particularly in the Midwest and West regions. Greater implementation of telehealth and involvement of primary care into opioid treatment practice offer possible solutions to eliminating geographical treatment barriers.