Effect of restricting the legal supply of prescription opioids on buying through online illicit marketplaces: interrupted time series analysis.

OBJECTIVE: To examine the effect on the trade in opioids through online illicit markets ("cryptomarkets") of the US Drug Enforcement Administration's ruling in 2014 to reschedule hydrocodone combination products. DESIGN: Interrupted time series analysis. SETTING: 31 of the world's largest cryptomarkets operating from October 2013 to July 2016. MAIN OUTCOME MEASURES: The proportion of total transactions, advertised and active listings for prescription opioids, prescription sedatives, prescription steroids, prescription stimulants, and illicit opioids, and the composition of the prescription opioid market between the US and elsewhere. RESULTS: The sale of prescription opioids through US cryptomarkets increased after the schedule change, with no statistically significant changes in sales of prescription sedatives, prescription steroids, prescription stimulants, or illicit opioids. In July 2016 sales of opioids through US cryptomarkets represented 13.7% of all drug sales (95% confidence interval 11.5% to 16.0%) compared with a modelled estimate of 6.7% of all sales (3.7% to 9.6%) had the new schedule not been introduced. This corresponds to a 4 percentage point yearly increase in the amount of trade that prescription opioids represent in the US market, set against no corresponding changes for comparable products or for prescription opioids sold outside the US. This change was first observed for sales, and later observed for product availability. There was also a change in the composition of the prescription opioid market: fentanyl was the least purchased product during July to September 2014, then the second most frequently purchased by July 2016. CONCLUSIONS: The scheduling change in hydrocodone combination products coincided with a statistically significant, sustained increase in illicit trading of opioids through online US cryptomarkets. These changes were not observed for other drug groups or in other countries. A subsequent move was observed towards the purchase of more potent forms of prescription opioids, particularly oxycodone and fentanyl.

Opioid Prescriptions in Older Medicare Beneficiaries After the 2014 Federal Rescheduling of Hydrocodone Products.

OBJECTIVES: To examine how an October 2014 Drug Enforcement Administration policy reclassified hydrocodone product from schedule III to II has affected older adults, who are among the largest consumers of prescription opioids in the United States. DESIGN: Retrospective cohort study. SETTING: United States. PARTICIPANTS: A 20% sample of Medicare Part D beneficiaries aged 65 and older from 2013 through 2015 (> 2,500,000 beneficiaries each year) MEASUREMENTS: From January 2013 to December 2015, we calculated the monthly prevalence of opioid prescriptions and the prevalence of individuals who received prescriptions for a 90-day supply or longer (prolonged), as well as hospitalizations related to opioid toxicity in 2013 and 2015. RESULTS: From 2013 to 2015, the proportion of Medicare Part D enrollees who received a hydrocodone prescription in a year decreased from 21.9% to 18.3%. Monthly rates for hydrocodone prescriptions declined significantly in 2014. The risk of receiving prolonged opioid prescriptions decreased by approximately 7% in the multivariable analyses comparing 2015 to 2013 (prevalence ratio=0.93, 95% confidence interval (CI)=0.93-0.94). Medicare enrollees with an original entitlement because of disability or with Medicaid eligibility had smaller decreases in prolonged prescriptions and, unexpectedly, small increases in high-dose prescriptions. Opioid-related hospitalizations did not change significantly, but opioid-related hospitalizations without a documented opioid prescription increased (odds ratio=1.24, 95% CI=1.03-1.50). CONCLUSION: The 2014 change in hydrocodone from schedule III to schedule II was associated with modest decreases in rates of opioid use in the elderly. The unexpected increase in opioid-related hospitalizations without documented opioid prescriptions may represent an increase in illegal use.

Impact of the Hydrocodone Schedule Change on Opioid Prescription Patterns in South Dakota.

INTRODUCTION: Prescription opioid use is becoming increasingly common; consequently, opioid overdose deaths are increasing at an alarming rate. Hydrocodone, one of the most commonly abused opioids, was changed from a schedule III controlled substance to the more stringent schedule II to decrease abuse and diversion, effective Oct. 6, 2014. The objective of this study was to examine the impact of the hydrocodone schedule change on opioid prescribing in South Dakota. METHODS: Opioid prescription patterns were examined in the following six-month phases: the baseline phase before the change, the transition phase when existing hydrocodone prescriptions could still be refilled, and the final phase. The South Dakota Board of Pharmacy Prescription Drug Monitoring Program provided aggregate monthly data for South Dakota opioid prescriptions (i.e., total number of prescriptions and days supplied), including urban and rural stratification. T-tests were performed on the monthly values for each phase to determine the significance of differences in prescription features between phases. RESULTS: The number of hydrocodone prescriptions significantly decreased 14 percent from baseline to final phase, while the days supplied per prescription significantly increased 7.4 percent. These changes were greater in rural areas than in urban areas. Conversely, the number of other opioid prescriptions significantly increased by 6.5 percent over this timeframe. CONCLUSIONS: The number of hydrocodone prescriptions decreased, while the days supplied per prescription increased. These changes were greater in rural areas than in urban areas. In addition, the number of other opioid prescriptions increased. These trends may reflect some unintended effects of the schedule change.

Zohydro approval by food and drug administration: controversial or frightening?

The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health consequences, despite numerous regulations enforced by multiple organizations. The approval of Zohydro and its defense from the FDA were based on a misunderstanding of the prevalence of chronic severe disabling pain. Based on inaccurate data from the Institute of Medicine, in part caused by conflicts of interest, 100 million persons have been described to suffer from severe pain - the correct number is 22.6 million. This manuscript analyzes 3 important principles of drug approval and utilization based on safety, efficacy, and medical necessity. Based on the limited literature that the authors were able to review including that which was submitted to the FDA by the manufacturers, it appears the safety, efficacy, and medical necessity were not demonstrated. In fact, the study submitted to the FDA showed a 50% pain improvement in only 48% of the patients in the treatment group and 21% of the patients in the placebo group at 85 day follow-up. This is a statistically significant result but its clinical relevance is unknown. The FDA approval decision occurring against the backdrop of the advisory panel recommendation is concerning and may result in serious consequences in the future.

The epidemiologic association between opioid prescribing, non-medical use, and emergency department visits.

INTRODUCTION: Since the 1990s prescriptions for and the non-medical use of opioids have increased. This study examines associations between opioid prescribing, non-medical use, and emergency department (ED) visits. METHODS: Data were abstracted from four federally sponsored, nationally representative, annual surveys (National Hospital Ambulatory Medical Care Survey, National Ambulatory Medical Care Survey, National Survey on Drug Use and Health, and Drug Abuse Warning Network). RESULTS: For hydrocodone and oxycodone, associations between prescribing and non-medical use, and prescribing and ED visits were statistically significant (p-values < 0.04) and strongly associated (correlation coefficient range 0.73 to 0.87). Male gender, White race, and age > or = 35 were all statistically significant (p-values < 0.0001) predictors of receiving a hydrocodone or oxycodone-containing prescription. CONCLUSION: The increased number of prescriptions written for hydrocodone and oxycodone between 1995 and 2004 was associated with similar increases in non-medical use and the number of ED visits during this time period.

The availability of web sites offering to sell opioid medications without prescriptions.

OBJECTIVE: This study was designed to determine the availability of web sites offering to sell opioid medications without prescriptions. METHOD: Forty-seven Internet searches were conducted with a variety of opioid medication terms, including "codeine," "no prescription Vicodin," and "OxyContin." Two independent raters examined the links generated in each search and resolved any coding disagreements. The resulting links were coded as "no prescription web sites" (NPWs) if they offered to sell opioid medications without prescriptions. RESULTS: In searches with terms such as "no prescription codeine" and "Vicodin," over 50% of the links obtained were coded as "NPWs." The proportion of links yielding NPWs was greater when the phrase "no prescription" was added to the opioid term. More than 300 opioid NPWs were identified and entered into a database. CONCLUSIONS: Three national drug-use monitoring studies have cited significant increases in prescription opioid use over the past 5 years, particularly among young people. The emergence of NPWs introduces a new vector for unregulated access to opioids. Research is needed to determine the effect of NPWs on prescription opioid use initiation, misuse, and dependence.