Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration.

BACKGROUND: Prescription opioid abuse and misuse is a serious and growing public health issue. While the most common form of abuse is swallowing intact tablets/capsules, some abusers manipulate, or tamper with, these medications by altering the dosage form to allow for non-oral routes of administration (e.g., injection, inhalation) in order to achieve more rapid or enhanced psychoactive effects. Because administration of opioids via non-oral routes results in greater systemic availability and more rapid central nervous system penetration, we hypothesized that death and major medical outcomes occur more frequently with non-oral routes compared to oral route alone. METHODS: This retrospective cohort study analyzed data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center Program to investigate relative risk of prescription opioid abuse via oral and non-oral routes. RESULTS: While the oral route was the most commonly reported route of abuse (64.0%), non-oral routes were reported in 14.6% exposures and unknown routes in 21.4% exposures. The relative risk of an exposure resulting in death or major effect was 2.43 (95% CI 1.97, 2.99) if non-oral routes were reported compared to exposures involving oral route only. CONCLUSION: Analysis of acute health events recorded by poison centers indicates that death or major effects are twice as likely to occur with intentional abuse of prescription opioids via non-oral routes of administration than ingestion alone. Effective interventions to prevent abuse via non-oral routes of solid dosage forms of prescription opioids, such as abuse-deterrent formulations could have a significant public health impact.

2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report.

BACKGROUND: This is the 30(th) Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of July 1, 2012, 57 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 7.58 [6.30, 11.22] (median [25%, 75%]) min, creating a near real-time national exposure and information database and surveillance system. METHODOLOGY: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 34 medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death. RESULTS: In 2012, 3,373,025 closed encounters were logged by NPDS: 2,275,141 human exposures, 66,440 animal exposures, 1,025,547 information calls, 5,679 human confirmed nonexposures, and 218 animal confirmed nonexposures. Total encounters showed a 6.9% decline from 2011, while healthcare facility (HCF) exposure calls increased by 1.2%. All information calls decreased by 14.8% and HCF information calls decreased by 1.7%, medication identification requests (Drug ID) decreased by 22.0%, and human exposures reported to US PCs decreased by 2.5%. Human exposures with less serious outcomes have decreased by 3.7% per year since 2008, while those with more serious outcomes (moderate, major, or death) have increased by 4.6% per year since 2000. The top five substance classes most frequently involved in all human exposures were analgesics (11.6%), cosmetics/personal care products (7.9%), household cleaning substances (7.2%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%). Analgesic exposures as a class increased the most rapidly (8,780 calls/year) over the last 12 years. The top five most common exposures in children aged 5 years or less were cosmetics/ personal care products (13.9%), analgesics (9.9%), household cleaning substances (9.7%), foreign bodies/toys/ miscellaneous (7.0%), and topical preparations (6.3%). Drug identification requests comprised 54.4% of all information calls. NPDS documented 2,937 human exposures resulting in death with 2,576 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response, and situational awareness tracking. NPDS is a model system for the nation and global public health.

Do prescription monitoring programs impact state trends in opioid abuse/misuse?

OBJECTIVE: Prescription monitoring programs (PMPs) are statewide databases containing prescriber and patient-level prescription data on select drugs of abuse. These databases are used by medical professionals or law enforcement officials to identify patients with prescription drug use patterns indicative of abuse or providers engaging in illegal activities. Most states have implemented PMPs in an attempt to curb prescription drug abuse and diversion. However, assessment of their impact on drug abuse is only beginning. This study aimed to evaluate the relationship between PMPs and opioid misuse over time in two drug abuse surveillance data sources. METHODS: Data from the RADARS® System Poison Center and Opioid Treatment surveillance databases were used to obtain measures of abuse and misuse of opioids. Repeated measures negative binomial regression was applied to quarterly surveillance data (from 2003 to mid-2009) to estimate and compare opioid abuse and misuse trends. PMP presence was modeled as a time varying covariate for each state. RESULTS: Results support an association between PMPs and mitigated opioid abuse and misuse trends. Without a PMP in place, Poison Center intentional exposures increased, on average, 1.9% per quarter, whereas opioid intentional exposures increase 0.2% (P = 0.036) per quarter with a PMP in place. Opioid treatment admissions increase, on average, 4.9% per quarter in states without a PMP vs 2.6% (P = 0.058) in states with a PMP. In addition to the time trend, population and a measure of drug availability were also significant predictors. A secondary analysis that classified PMP based upon ideal characteristic showed consistent though not significant results. CONCLUSIONS: Two observational data sources offer preliminary support that PMPs are effective. Future efforts should evaluate what PMP characteristics are most effective and which opioids are most impacted.

Prescription drugs purchased through the internet: who are the end users?

Although prescription drugs are readily available on the Internet, little is known about the prevalence of Internet use for the purchase of medications without a legitimate prescription, and the characteristics of those that obtain non-prescribed drugs through online sources. The scientific literature on this topic is limited to anecdotal reports or studies plagued by small sample sizes. Within this context, the focus of this paper is an examination of five national data sets from the U.S. with the purpose of estimating: (1) how common obtaining prescription medications from the Internet actually is, (2) who are the typical populations of "end users" of these non-prescribed medications, and (3) which drugs are being purchased without a prescription. Three of the data sets are drawn from the RADARS (Researched Abuse Diversion and Addiction-Related Surveillance) System, a comprehensive series of studies designed to collect timely and geographically specific data on the abuse and diversion of a number of prescription stimulants and opioid analgesics. The remaining data sets include the National Survey on Drug Use and Health (NSDUH) and the Monitoring the Future (MTF) survey. Our analysis yielded uniformly low rates of prescription drug acquisition from online sources across all five data systems we examined. The consistency of this finding across very diverse populations suggests that the Internet is a relatively minor source for illicit purchases of prescription medications by the individual end-users of these drugs.

Integrating nine prescription opioid analgesics and/or four signal detection systems to summarize statewide prescription drug abuse in the United States in 2007.

PURPOSE: Integrate statewide rankings of abuse across different drugs and/or signal detection systems to summarize prescription drug abuse in each state in 2007. METHODS: Four signal detection systems (Opioid Treatment Programs, Key Informants, Drug Diversion, and Poison Centers) that covered heterogeneous populations collected data on the abuse of nine opioids: hydrocodone, immediate-release oxycodone, tramadol, extended-release [ER] oxycodone, fentanyl, morphine, methadone, hydromorphone, and buprenorphine). We introduce here linearized maps which integrate nine drugs within each system; four systems for each drug; or all drugs and systems. RESULTS: When rankings were integrated across drugs, Rhode Island, New Hampshire, Maine, West Virginia, and Michigan were in the highest tertile of abuse in three systems. When rankings were integrated across signal detection systems, there was a geographic clustering of states with the highest rates for ER oxycodone (in Tennessee, Mississippi, Kentucky, Ohio, Indiana, Michigan, and in Massachusetts, New Hampshire, Maine, and Vermont) and methadone (Massachusetts, Rhode Island, New Hampshire, Maine, Vermont, Connecticut, and New Jersey). When rankings were integrated across both drugs and signal detection systems, states with 3-digit ZIP codes below 269 (i.e., from Massachusetts to West Virginia): Massachusetts, New Hampshire, Maine, Vermont, Washington DC, Virginia, and West Virginia were in the highest tertile and only Delaware was in the lowest tertile. CONCLUSIONS: We have presented methods to integrate data on prescription opioid abuse collected by signal detection systems covering different populations. Linearized maps are effective graphical summaries that depict differences in the level of prescription opioid abuse at the state level.

The underrecognized toll of prescription opioid abuse on young children.

STUDY OBJECTIVE: The impact of prescription opioid abuse on young children is underrecognized and poorly documented. We hypothesize that poisoning of young children from prescription opioids occurs regularly in the United States and is associated with serious health events, including death. METHODS: Using data from poison centers participating in the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System, exposures in children younger than 6 years, involving buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone (January 2003 to June 2006), were quantified and described. RESULTS: We identified 9,179 children exposed to a prescription opioid. The median age was 2.0 years (range newborn to 5.5 years), and 54% were boys. Nearly all exposures involved ingestion (99%) and occurred in the home (92%). Exposures to any opioid were associated with 8 deaths, 43 major effects, and 214 moderate effects. Of 51 patients who experienced a major effect or death, 35 were treated with naloxone: a beneficial response was documented in 34 patients. All 5 exposures to buprenorphine associated with a major effect were treated with naloxone, and a beneficial response was recorded in all 5. Nearly all exposures were to medications prescribed for adults in the household. The number of prescriptions filled for an opioid in an area correlated well with exposures in young children in the same area; children have access to household members' prescription drugs. CONCLUSION: Young children are exposed to prescription opioids, typically prescribed for other patients, resulting in major health effects and death.

Abuse of buprenorphine in the United States: 2003-2005.

This study examines trends in the reported abuse of two sublingual buprenorphine products, Subutex and Suboxone, in the United States. Quarterly counts of abuse cases were obtained from 18 regional poison control centers (PCCS) for 2003-2005. Seventy-seven abuse cases were reported, of which 7.8 percent involved Subutex and 92.2 percent involved Suboxone. The average quarterly ratio of abuse cases per 1,000 prescriptions dispensed was 0.08 (SD +/- 0.09) for Subutex, and 0.16 (SD +/- 0.08) for Suboxone. Findings suggest that these sublingual buprenorphine formulations have a low rate of abuse based on toxico-surveillance data.

The effect of FDA approval of a generic competitor to OxyContin (oxycodone HCl controlled-release) tablets on the abuse of oxycodone.

Controversy exists concerning whether abuse of oxycodone will increase after the introduction of generic controlled-release (CR) oxycodone. We evaluated the effect of FDA approval of generic CR oxycodone on the misuse/abuse of oxycodone, hydrocodone, methadone and morphine utilizing data from eight poison control centers (PCC). PCC intentional exposure (IE) reason codes were used as measures of abuse. Opioid-specific quarterly IE rates (per 100,000 population and per 10,000 patients) were calculated for 1 year before and after approval (March 24, 2004). Changes in regression slopes (1 year before to 1 year after) and in IE rates (1 quarter before to 1 quarter after) were analyzed using Poisson regression. The regression slopes for oxycodone, methadone and morphine did not change after approval but decreased significantly for hydrocodone. None of the prescription opioids' IE rates significantly increased after approval. When changes in oxycodone's IE rates were compared to the other opioids, no statistically significant differences were found, indicating a lack of time-opioid interaction. These results did not vary when population rates or patient rates were used. PCC data indicate that approval of generic CR oxycodone was not followed by an immediate unfavorable effect on the misuse/abuse of oxycodone.