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Biomedical subjects

J David Haddox

Publications and source records attributed to J David Haddox.

10 recordsLinked to original sources
PubMed2006

Risk identification, risk assessment, and risk management of abusable drug formulations.

There is a demand for pharmaceutical products with reduced abuse liability. These products must meet three tests to be successful. They must be safe for patients, be less likely to injure the abuser, and be less desirable for abuse by established drug abusers relative to existing products on a dose for dose (milligram-equivalent) basis. There is a need for standardization of the evaluation of abusable pharmaceuticals in the various stages of drug development from preclinical animal studies to postmarketing surveillance. Formulations with reduced abuse liability must: (1) be tested using standard animal, benchtop, and human pharmacokinetic methods that allow interpretation, (2) sufficiently reduce the recovery of abusable drug substance, or contain another ingredient to deter abuse, (3) not alter drug activity for patients in an undesirable or risky way, and (4) have an accurate pre-approval estimation of their reduced abuse liability, which is validated by adequate epidemiologic post-approval surveillance.

Chemistry, Pharmaceutical↗
PubMed2005

Association between non-medical and prescriptive usage of opioids.

Understanding and managing prescription opioid abuse is one of the major challenges in pain management worldwide. The relationships between prescriptive usage of opioids and reported morbidity at the national level, using data from the Drug Abuse Warning Network (DAWN), were examined. When the major prescription opioids were evaluated, the association between prescriptive medical use in kilograms and reported morbidity, as measured by a ratio between the two, was similar for the intermediate-potency opioids (hydrocodone, methadone, oxycodone, and morphine). This rate was much lower for low-potency opioids (codeine, meperidine, pentazocine, and propoxyphene) and much greater for high-potency opioids (hydromorphone and fentanyl). When the drugs were adjusted by potency (relative to morphine), the rates of reported morbidity per kilogram of morphine equivalent opioid in prescriptive usage were similar among the opioids. Using the potency-adjusted total kilograms of opioid in prescriptive use for all the opioids evaluated, there was a statistically significant association (r(2)=0.9791) with the reported morbidity for prescription analgesics as a class, as measured in the DAWN system. These data suggest that non-medical use of opioids is predictable based on potency and extent of prescriptive use.

Analgesics↗
PubMed2004

Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions.

Recent surveys suggest that the abuse of drugs, often in combination, is pervasive throughout society. Adverse consequences of drug abuse tend to be attributed to the single drug "most likely" to be responsible. This is frequently seen in fatality cases, particularly those involving opioids. However, it is difficult to determine the specific cause of death when multiple drugs are involved. Although enhanced toxicity of alcohol and other centrally acting drugs with opioids has been well established in animal studies, there is a paucity of data in well-controlled human studies. We evaluated 1014 fatality cases involving oxycodone (OXC) for evidence of enhanced toxicity associated with multiple drug-drug interactions. We previously reported on these cases, and we classified them by a standardized method into groups that distinguished cases unrelated to drug abuse from those related to drug abuse, cases that involved only OXC from cases involving multiple drugs, drug-induced fatalities from drug-related fatalities, and cases in which the specific drug product OxyContin (oxycodone HCl controlled-release) Tablets were identified from cases where OxyContin was not identified. Our working hypothesis was that OXC in combination with other centrally acting drugs is more toxic than OXC alone, evidenced by the finding of lower mean blood concentrations of OXC in multiple-drug-induced deaths compared to single (OXC only)-drug-induced deaths. Assessment of blood levels determined by specific assay methodology (primarily gas chromatography-mass spectrometry) in these cases provided the following mean postmortem concentrations of OXC: multiple-drug-induced deaths, OxyContin identified, 0.93 microg/mL (N = 167); multiple-drug-induced deaths, OxyContin not identified, 0.73 microg/mL (N = 579); single (OXC)-drug-induced deaths, OxyContin identified, 1.55 microg/mL (N = 12); and single (OXC)-drug-induced deaths, OxyContin not identified, 1.70 microg/mL (N = 15). Overall, mean OXC concentration trends were as follows: single (OXC)-drug-induced, drug-abuse deaths > multiple-drug-induced drug-abuse deaths > drug-related drug-abuse deaths approximately deaths unrelated to drug abuse; and deaths in which OxyContin was identified approximately deaths in which OxyContin was not identified, whether the deaths involved oxycodone alone or multiple drugs. Drug abuse patterns in the multiple-drug-induced cases were complex. Over 135 drugs that were considered to be plausibly contributory to enhanced toxicity were identified in body fluids and tissues. Evaluation of mean OXC blood concentrations in cases that contained one, two, three, four, five, and six or more contributory drugs in combination demonstrated consistently lower mean OXC concentrations than those cases in which OXC was the only drug identified. A smaller number of cases were evaluated in the multiple-drug-induced groups in which OXC was paired with a single other contributory drug. The overall mean OXC concentration for these cases was 0.71 microg/mL (N = 90) as compared to 1.64 microg/mL (N = 27) for the cases in the single drug-induced groups. The consistent finding of lower mean OXC blood levels associated with multiple-drug-induced fatalities supports the stated hypothesis that OXC in combination with other centrally active drugs is more toxic than when OXC was the only drug involved. It was concluded that in cases of multiple-drug fatalities, cause of death (COD) should not be attributed to any single drug. Rather, the unique combination of drugs, the pattern of drug use/abuse, and individual factors, such as tolerance to the respiratory depressant effects of opioids, must be taken into account in arriving at a valid COD statement.

Cause of Death↗
PubMed2004

Identifying controlled substance patterns of utilization requiring evaluation using administrative claims data.

OBJECTIVES: To develop a systems approach to identify, for further evaluation, patients with potential controlled substance misuse or mismanagement using software queries applied to administrative health claims data. STUDY DESIGN: Retrospective validation of the system using insurance claims. PATIENTS AND METHODS: Data from administrative health claims databases representing nearly 7 million individuals younger than 65 years were used by multidisciplinary expert panels to develop and validate controlled substance patterns of utilization requiring evaluation (CS-PURE) criteria. RESULTS: Thirty-four CS-PURE queries were developed in SAS and applied to administrative claims records to identify patients with potential controlled substance misuse or mismanagement. From these, we identified 10 CS-PURE with the highest expert agreement that intervention was warranted. Expert panel agree, ment that CS-PURE correctly identified cases ranged from 48% to 100%, with at least 50% agreement in 9 of 10 CS-PURE. The prevalence rates for CS-PURE ranged from 0.001% to 0.252%. This translates to identifying between 5 and 1116 patients for individual CS-PURE in a 500 000-member health plan. CONCLUSIONS: We developed and empirically validated a group of queries using CS-PURE to identify patients with potential controlled substance misuse or mismanagement that would warrant further evaluation by the treating physician, a quality assurance function, or the medical director. Claims-based CS-PURE identification is generalizable to most health insurers with access to medical and pharmaceutical claims records. Although CS-PURE are not direct measures of misuse, they can direct attention to potential problems to determine if intervention is needed.

Adolescent↗
PubMed2003

Lawful prescribing and the prevention of diversion.

Concern about controlled substance diversion and overview of prescribers by legal and regulatory officials is growing. The article is designed to increase health professionals' awareness of the methods of diversion and to provide guidance on how diversion can be foiled. This paper also should help healthcare practitioners to better understand the regulations governing prescribing of controlled substances. Examples of unlawful prescribing of controlled substances are presented. Some behaviors of persons illegitimately seeking controlled substances from prescribers are described. Strategies to lessen the possibility of prescriptions being altered are discussed. Federal and state laws and regulations pertaining to controlled substances are described.

Drug Prescriptions↗
PubMed2003

Oxycodone involvement in drug abuse deaths: a DAWN-based classification scheme applied to an oxycodone postmortem database containing over 1000 cases.

An oxycodone postmortem database was created from 1243 solicited cases from Medical Examiner and Coroner (ME/C) offices in 23 states in the United States over the period from August 27, 1999, through January 17, 2002. The request for cases was specific to only those cases in which the ME/C opined that the death involved oxycodone. Each case was evaluated to determine the role of oxycodone and the specific drug product OxyContin tablets in the death. Oxycodone identification was based on toxicology testing, and OxyContin identification was based on evidence found at the scene, credible witness reports, or identification of tablets in gastrointestinal contents. A system of case categorization was developed for this study based on the Drug Abuse Warning Network (DAWN) system for reporting drug abuse mortality data in the United States, using the same standardized, well-understood terminology. Of the 1243 cases, 79 cases were incomplete and could not be evaluated. There were an additional 150 cases submitted in which oxycodone was not identified by the originating ME/C. Of the remaining 1014 cases, 919 (90.6%) were related to drug abuse, whereas 95 (9.4%) cases were categorized as not involving drug abuse. Only 30 (3.3%) of the drug abuse cases involved oxycodone as the single reported chemical entity; of these, 12 cases had OxyContin identified as a source of oxycodone. Of the 919 drug abuse cases, the vast majority (N = 889, 96.7%) were multiple drug abuse deaths in which there was at least one other plausible contributory drug in addition to oxycodone. The most prevalent drug combinations were oxycodone in combination with benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants. Using the DAWN definitions, drug abuse cases were further categorized as drug-induced or drug-related. A total of 851 (92.6%) cases met the criteria for classification as being drug-induced, and the remaining 68 (7.4%) cases were categorized as drug-related. Cause of death (COD) statements from the originating ME/C indicated a general recognition of the role of abuse of multiple drugs in causing fatalities. Approximately 70% of the 889 cases in the multiple-drug-induced categories were listed in the COD or contributing COD statements as multiple-drug deaths. A variety of terms were employed in the COD statements to indicate multiple drug involvement such as "polydrug toxicity", "polypharmacy", "multiple drug poisoning", and "polypharmaceutical overdose". The system for death classification employed in this study recognizes the problems inherent in COD attribution when multiple drugs are involved. Use of this new system for reporting mortality data in future studies involving opioids is recommended.

Adult↗
PubMed2002

Pain management, controlled substances, and state medical board policy: a decade of change.

Physicians' concerns about regulatory scrutiny and the possibility of unwarranted investigation by regulatory agencies negatively affect their prescribing of opioid analgesics to treat pain. Indeed, some state medical boards have rejected prescribing practices that are considered acceptable by today's standards. This article describes a ten-year program of research, education, and policy development implemented by the Pain & Policy Studies Group aimed at updating and clarifying state medical board policies on the use of opioid analgesics to treat pain, including cancer and chronic noncancer pain. Following surveys of medical board members and educational workshops, state medical board policies began an initial period of change, drawing on guidelines from other states, particularly in California. The next phase of policy development was marked by the introduction of Model Guidelines by the Federation of State Medical Boards of the U.S. The Model Guidelines address professional standards for the appropriate prescribing of opioid analgesics for pain management, as well as physicians' fears of regulatory scrutiny. Although most state medical boards have adopted regulations, guidelines, or policy statements relating to controlled substances and pain management, to date ten boards have adopted the Model Guidelines, while ten more have adopted the Model Guidelines in part. Further actions are recommended so that state medical boards can address inadequate pain management and physician concerns about regulatory scrutiny.

Analgesics, Opioid↗
PubMedDate not supplied

Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions.

Recent surveys suggest that the abuse of drugs, often in combination, is pervasive throughout society. Adverse consequences of drug abuse tend to be attributed to the single drug "most likely" to be responsible. This is frequently seen in fatality cases, particularly those involving opioids. However, it is difficult to determine the specific cause of death when multiple drugs are involved. Although enhanced toxicity of alcohol and other centrally acting drugs with opioids has been well established in animal studies, there is a paucity of data in well-controlled human studies. We evaluated 1014 fatality cases involving oxycodone (OXC) for evidence of enhanced toxicity associated with multiple drug-drug interactions. We previously reported on these cases, and we classified them by a standardized method into groups that distinguished cases unrelated to drug abuse from those related to drug abuse, cases that involved only OXC from cases involving multiple drugs, drug-induced fatalities from drug-related fatalities, and cases in which the specific drug product OxyContin (oxycodone HCl controlled-release) tablets were identified from cases where OxyContin was not identified. Our working hypothesis was that OXC in combination with other centrally acting drugs is more toxic than OXC alone, evidenced by the finding of lower mean blood concentrations of OXC in multiple drug-induced deaths compared to single (OXC only) drug-induced deaths. Assessment of blood levels determined by specific assay methodology (primarily gas chromatography-mass spectrometry) in these cases provided the following mean postmortem concentrations of OXC: multiple drug-induced deaths, OxyContin identified, 0.93 mg/mL (N = 167); multiple drug-induced deaths, OxyContin not identified, 0.73 mg/mL (N = 579); single (OXC) drug-induced deaths, OxyContin identified, 1.55 mg/mL (N = 12); and single (OXC) drug-induced deaths, OxyContin not identified, 1.70 mg/mL (N = 15). Overall, mean OXC concentration trends were as follows: single (OXC), drug-induced, drug abuse deaths > multiple, drug-induced drug abuse deaths > drug-related drug abuse deaths approximately deaths unrelated to drug abuse; and deaths in which OxyContin was identified approximately deaths in which OxyContin was not identified, whether the deaths involved oxycodone alone or multiple drugs. Drug abuse patterns in the multiple drug-induced cases were complex. Over 135 drugs that were considered to be plausibly contributory to enhanced toxicity were identified in body fluids and tissues. Evaluation of mean OXC blood concentrations in cases that contained one, two, three, four, five, and six or more contributory drugs in combination demonstrated consistently lower mean OXC concentrations than those cases in which OXC was the only drug identified. A smaller number of cases were evaluated in the multiple drug-induced groups in which OXC was paired with a single other contributory drug. The overall mean OXC concentration for these cases was 0.71 mg/mL (N = 90) as compared to 1.64 mg/mL (N = 27) for the cases in the single drug-induced groups. The consistent finding of lower mean OXC blood levels associated with multiple drug-induced fatalities supports the stated hypothesis that OXC in combination with other centrally active drugs is more toxic than when OXC was the only drug involved. It was concluded that in cases of multiple drug fatalities, cause of death (COD) should not be attributed to any single drug. Rather, the unique combination of drugs, the pattern of drug use/abuse, and individual factors, such as tolerance to the respiratory depressant effects of opioids, must be taken into account in arriving at a valid COD statement.

Cause of Death↗