Effect of the market withdrawal of dextropropoxyphene on use of other prescribed analgesics
Authors: Reset Askild , Skurtveit Svetlana , Furu Kari , Skovlund Eva 
Published: August 2018

Abstract

Background and aims
Dextropropoxyphene (DXP) is a synthetic opioid that was prescribed worldwide for mild to moderate pain. It was withdrawn from the European market in 2009. In this study we aim to investigate the effect of the market withdrawal of dextropropoxyphene in Norway on overall use of opioids and other analgesics at an individual level.

Methods
Data were collected from the nationwide Norwegian Prescription Database (NorPD). It covers all prescription of drugs from 01 January 2004 from Norwegian pharmacies dispensed to individuals outside institutions. The study period was divided in two 2-year periods from 01 September 2008 to 31 August 2010, and from the market withdrawal of DXP on 01 September 2010 to 31 August 2012. We included every individual that filled at least one prescription of dextropropoxyphene in the first 2-year period in our study population. In this study dextropropoxyphene, codeine and tramadol are defined as “weak opioids”, and all other opioids are termed “strong opioids”.

Results
Nine thousand one hundred and seventy-one individuals were included in our study population. Four thousand two hundred and ninety filled a prescription of DXP only once and were classified as “single users”, 2,990 were users with prescriptions of up to 200 defined daily doses (DDD) over the first 2-year period, or “sporadic users”, and 1,886 were classified high users with over 200 DDDs over a 2-year period. After the market withdrawal 8,392 continued to be prescribed analgesics or benzodiazepines. In the single user group, the proportion of users of weak opioids decreased from 69.5% to 57.6%, whereas the proportion of users of strong opioids was unchanged. Among the sporadic user group, the proportion of users of weak opioids went from 69.7% to 71.0%, the proportion using tramadol from 39.1% to 43.9%, and the users of strong opioids from 25.8% to 31.3%. In the high user group, there was an increase in the number of users of strong opioids from 37.8% to 51.4%. The amount of strong opioids prescribed in the high user group increased from a mean of 262.5 DDD to a mean of 398.3 DDD in the following 2 years. The amount of tramadol increased in all groups and was 3 times as high in the high user group after market withdrawal of DXP.

Conclusions
Our study showed that the withdrawal of DXP lead to an increase in prescription of other analgesics. The proportion of users increased in all three groups and so did the prescribed amount of other analgesics. Both the proportion of users of other opioids and the amount prescribed increased considerably. However, 1 in 10 earlier users of DXP stopped using prescribed analgesics altogether in the following 2 years. The increase in use among earlier high users of DXP was most striking.

Implications
This study documents markedly increased prescriptions of other opioids after withdrawal of dextropropoxyphene due to its high risk of serious complications. However, consequences of the increased use of opioids among earlier high users of DXP such as changes in risk of poisonings, accidental deaths and suicides remain to be investigated.