A Forum for Improving Drug Safety

Considering that adverse drug reactions are the fourth leading cause of death- responsible for taking over 100,000 U.S. lives per year; you’d think the problem would get more attention. With the recent scare with Dennis Quaid’s children’s accidental heperin overdose and now Heath Ledger’s accidental overdose, maybe this serious public health problem will begin to get the coverage it deserves.  Perhaps Heath was one of the 10% of people that are 2D6 poor metabolizers greatly increasing his chances of ill effects from an already potentially dangerous combination of drugs. The drugs he was taking are central nervous system respiratory depressants, alone and worse together.

Oxycodone itself can be lethal. Easily testable genetic variants can compound this risk.There are a number of variables that may have lead to Ledger’s early and tragic death, but regardless of the cause, ADRs are a huge problem and we already have the tools to help reduce the risk, so why aren’t we using them?

Here’s an interesting reference on the increase in opioid use and fatal drug poisoning:  Am J Prev Med. 2006 Dec;31(6):506-11.

Opioid analgesics and rates of fatal drug poisoning in the United States.

Paulozzi LJ, Ryan GW.Division of Unintentional Injury Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. lbp4@cdc.gov

OBJECTIVE
To determine whether the variability in rate of sale of prescription opioid analgesics is related to the variability in rates of drug poisoning mortality among states in the United States in 2002.

METHODS
Drug poisoning deaths were defined as unintentional deaths or those of undetermined intent whose underlying cause was coded to “narcotics” (X42) or “other and unspecified” drugs (X44) in the National Vital Statistics System. Per capita sales of ten opioid analgesics from the Drug Enforcement Administration and combined sales in morphine equivalents were correlated with drug poisoning mortality rates by state using multivariate linear regression.Regression coefficients between mortality rates and sales rates were adjusted for race (percent white, percent black) and age (percent aged 24 years or younger, and percent aged 65 years and older).

RESULTS
There was over a ten-fold variability in sales of some opioid analgesics. Combined sales ranged 3.7-fold, from 218 mg per person in South Dakota to 798 mg per person in Maine. Drug poisoning mortality varied 7.9-fold, from 1.6/100,000 in Iowa to 12.4/100,000 in New Mexico. Drug poisoning mortality correlated most strongly with non-OxyContin oxycodone (r=0.73, p<0.0001), total oxycodone (r=0.68, p<0.0001), and total methadone (r=0.66, p<0.0001) in the multivariate analysis. A scatterplot demonstrated a linear relationship between total opioid analgesic sales and drug poisoning mortality.

CONCLUSIONS
The extent of opioid analgesics use varies widely in the United States. Variation in the availability of opioid analgesics is related to the spatial distribution of drug poisoning mortality by state.

PMID: 17169712 [PubMed - indexed for MEDLINE]Related Links

* Increasing deaths from opioid analgesics in the United States. [Pharmacoepidemiol Drug Saf. 2006]

* Surveillance of prescription drug-related mortality using death certificate data. [Drug Saf. 2007]

* Geographic variation in the prescription of schedule II opioid analgesics among outpatients in the United States. [Health Serv Res. 2006]

* Association between availability of heroin and methadone and fatal poisoning in England and Wales 1993-2004. [Int J Epidemiol.2006]

* Trends in abuse of Oxycontin and other opioid analgesics in the United States: 2002-2004. [J Pain. 2005]