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5PSQ-048 Darunavir/cobicistat pharmacological interactions: clinical relevance and action mechanism

Background Darunavir/cobicistat (DRV/COB) is the first fixed combination inhibitor of protease. Both are metabolised by the cytochrome CYP3A4, the reason why they are susceptible to present a multitude of drug interactions (DI). Purpose To describe the DI of DRV/COB in HIV patients to avoid and to optimise therapy. Material and methods Retrospective observational study performed in a county hospital. We reviewed the digital clinical history to collect the following data: patients treated with DRV/COB from 1 January 2016 to 1 November 2016, demographics, duration of treatment, concomitant medications, drugs involved, and DI. We review HIV-drug interactions using the database of the University of Liverpool to classify DI according to the mechanism of action (MA) and their potential severity. The pharmaceutical intervention (PI) was to notify to the prescribing physician, by report attached in the patient’s medical record, the contraindicated interactions (CI). Results Thirty-five patients, 51% males (n=18). Race: 54% non-Caucasian (n=19). Median age 37 years (IQR 64–20). Median days of treatment 195 (IQR 465–22), total of concomitant medications 199, median 5 (IQR 1–19), DI 31% (n=62) median 1 (IQR 0–8), 40 drugs involved in DI. Type of DI according to their MA: CYP3A inhibition 62% (n=25), inhibition CYP2D6 10% (n=4), inhibition CYP3A and CYP2D6 7% (n=3) and inducer CYP3A 5% MA 15% (n=6). DI type according to its potential severity: high (CI) 15% (n=6) (midazolam, budesonide, phenobarbital, ivabradine, simvastatin and domperidone); and potential: 89% (n=35). PI: accepted 3 (50%): one change from simvastatin to rosuvastatin, one change from phenobarbital to levetiracetam and a change from midazolam to lormetazepam. Conclusion A high rate of DI is observed in patients receiving treatment with DRV/COB. The most relevant interactions are observed at the level of the CYP3A family. Acceptance of PI was low in the case of CI detected, probably because the prescribing physician was unaware of it. To have a higher success rate we could have made a phone call to him to put him on notice. The pharmacist is important in optimising drug therapy. References and/or Acknowledgements Thanks to all my colleagues in the Hospital de Poniente for their selfless help No conflict of interest