Early in the 1970s there were warnings from FDA about the risk of DXP toxicity in US. Report of fatalities due to DXP led to an information campaign 1978-1980 - but Eli Lilly didn´t do what FDA had expected

In 2001 - after our dissertations 2000 and 2001 - we published the following book in English. Fatalities due to use or misuse of pain-killers, written by Birgitta Jonasson and Ulf Jonasson in collaboration with the National Board of Forensic Medicine in Sweden, RMV-report 2001:1. We have scanned the book in one of my blogs – http://bit.ly/34051yX at my blog http://jonassonulf.blogspot.com .

The year 1999 we wrote “Dödsfall genom bruk och missbruk av värktabletter” RMV Rapport 1999:1, the Swedish version

In chapter 3 - International experiences and measures taken – we present different countries and how their story of (Dextro) (Propoxyphene) DXP has been. These countries are USA, UK, Denmark, Norway, Sweden and Australia

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There are a several articles that are of greatest interest, for example:

·        DXP – field of application and toxicity

·        International experiences and measures taken

·        Dependence of DXP

·        Summary, discussion and conclusion

DXP in the United States

Early in the 1970s warnings about the risk of DXP toxicity and about the potentiating action of alcohol on the DXP effect were issued in the USA on the bases of clinical reports (37). It was concluded that physicians should be alerted to the potential deleterious effects of indiscriminate use and abuse of DXP - and should warn their patients not to drink alcohol when taking DXP. It was recommended that physicians should observe extreme caution when prescribing DXP to young people.

In extensive surveys it was found that the number of deaths involving DXP was increasing each year, and at a faster rate than the total drug deaths. Deaths attributed to suicide, as well as those judged to be accidental deaths and undetermined deaths had increased (35, 38-40). DXP, according to these studies, did not appear to be a paediatric problem. 

Nor did the deceased persons belong to the illegal drug abuse population or have any particular propensity for the use of heroin or narcotics. Rather they constituted a particular medical population of those who misuse prescription drugs and alcohol. Almost all of them received a wide range of prescription drugs, particularly tranquillisers, which they often misused by self-medication, multiple drug ingestion, and combining alcohol with their medication.

Information campaign in 1978-80 due to DXP

The reports of fatalities due to DXP led to an information campaign in 1978-80 undertaken by the US Food and Drug Administration (FDA) and the drug’s manufacturer through mailed warnings, face-to-face education of prescribers, press- releases, and labelling changes. The goal was to reduce simultaneous use of DXP and alcohol or other CNS depressants, to reduce the prescription of refills, and to get physicians to stop prescribing DXP for patients at risk of abuse and misuse.

Trends in prescribing and deaths related to DXP overdose before and after this campaign were analysed by Soumerai and collaborators (14). They found that a pre-existing downward trend of about 8% per year continued during the warnings, but halted after them. The no-refill recommendations had no effect on the refill rates. They also noted that the overdose death per DXP prescription had remained about constant since 1979, and considered that stronger, more sustained regulatory or educational measures had to be implemented to achieve any sharper reductions in the misuse of the drug. 

Further, they suggested that the wide extent of DXP use is mainly due to its overall popularity in relation to competitive products, probably largely on account of effective marketing activities. One example of these activities is described in their report:

As FDA had no ongoing physician education programme of its own, it requested that the manufacturer of DXP should revise the drug labelling and conduct both a mailed and a person-to-person educational campaign. Eli Lilly and Company sent a mailed warning message to 145,000 physicians, but when it came to the face-to-face education an investigation conducted by an FDA official showed that Eli Lilly did not fulfil this commitment. It was only in less than 10% of the "face-to-face educational occasions" that the detailers conveyed suitable information on the new warnings; while over 75% of the detailers left free samples of DXP products on those particular occasions. 

The FDA official quoted several verbatim messages from Lilly detailers recorded by physicians. “Darvon and Lilly won FDA battle”, “Safe in spite of Nader report”, “OK by the Drug Commission”, “Few if any side effects”.