CYP2D6-Inhibiting Drugs and the Increased Risk of Fall-Related Injuries Due to Newly Initiated Opioid Treatment - A Swedish, Register-Based Case-Crossover Study

It has been shown that newly initiated opioid therapy increases the risk of fall-related injuries. Yet, it remains to be determined whether drug-drug interactions can affect this negative effect, for instance with drugs inhibiting cytochrome P4502D6 (CYP2D6) that metabolizes codeine and also has a partial effect on tramadol and oxycodone. Our aim was to investigate how CYP2D6-inhibiting drugs contribute to explaining the risk of fall-related injuries for newly initiated opioid treatments with codeine, tramadol or oxycodone. Data from a Swedish national case-cross over study were revisited. This study identified a total of 167,257 fall-related injuries leading to hospitalization that occurred between 1 May 2006 and 31 December 2009 and linked information about dispensed drugs to them. Use of newly dispensed opioids in the 28days before fall-related injury with and without CYP2D6-inhibiting drugs was compared with an earlier control period. For codeine, there was a two-times increased risk with concomitant CYP2D6-inhibiting drug use (OR, 1.76; 95% CI 1.40-2.20) and a three-times risk increase without (OR, 3.17; 95% CI 2.88-3.50). For tramadol, the risks were doubled when CYP2D6-inhibiting drugs were used (OR, 2.19; 95% CI 1.84-2.60) and tripled without their use (OR, 3.04; 95% CI 2.82-3.27). The risks were about the same for oxycodone, morphine, fentanyl and buprenorphine irrespective of CYP2D6-inhibiting drug use. In newly initiated opioid therapies, drug-drug interactions from concomitant use of CYP2D6-inhibiting drugs are associated with a lower risk of fall-related injury for codeine and tramadol that undergo metabolism via CYP2D6, but not for other opioids.