Frequency and clinical relevance of potential cytochrome P450 drug interactions in a psychiatric patient population - An analysis based on German insurance claims data

Abstract

Background: Numerous drugs used in the treatment of psychiatric disorders are substrates of cytochrome P450 enzymes and are potential candidates for drug-drug interactions (DDIs). Methods: Claims data of a German statutory health insurance company from severely mentally ill patients who registered in an integrated care contract from August 2004 to December 2009 were analysed. We measured time periods of concomitant prescription of drugs that have been reported to interact via cytochrome P450, with a focus on drugs acting as strong inhibitors. Such drug-drug exposure (DDE) is an incontrovertible precursor of DDIs. We assessed whether potential DDIs were considered clinically relevant based on the prescribing information of the respective drugs. Results: Among all 1221 patients, 186 patients (15.2 %; Clopper-Pearson 95 % confidence interval (CI): 13.3-17.4 %) had at least one DDE prescription, and 58 patients (4.8 %; 95 % CI 3.6-6.1) had at least one DDE prescription involving a strong cytochrome P450 inhibitor. In 59 patients, (4.8 %; 95 % CI: 3.7-6.2 %) five or more DDEs were identified, and five or more DDEs with a strong inhibitor were identified in 18 patients (1.5 %; 95 % CI: 0.9-2.3). The rates of DDEs were 0.27 (Garwood 95%CI: 0.25-0.28) per person-year and 0.07 (95 % CI: 0.07-0.08) for strong-inhibitor DDEs. Four of the ten most frequent DDEs were identified as clinically relevant, and seven of the eight most frequent DDEs involving a strong inhibitor were clinically relevant. Conclusions: The number of patients with DDEs was not alarmingly high in our sample. Nevertheless, prescription information showed that some prescribed drug combinations could result in serious adverse consequences that are known to weaken or strengthen the effect of the drugs and should therefore be avoided.