Pharmacokinetic enhancers (cobicistat/ritonavir) and the potential for drug-drug interactions
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The potential for clinically significant drug interactions (CSDIs) for patients taking ritonavir and cobicistat is high because of their powerful pharmacokinetic effect on the cytochrome P450 (CYP) enzyme system, most notably their inhibitory effect on CYP3A4.
An audit was conducted to measure and correct for patients exposed to potentially dangerous drug interactions.
Two hundred individuals attending a regional specialist human immunodeficiency virus (HIV) clinic between June and September 2014 who were receiving the pharmacokinetic enhancers ritonavir or cobicistat were interviewed to determine a medication history including medications prescribed by their general practitioner (GP), over-the-counter (OTC) medicines, herbal remedies and recreational drugs.
Of the 200 patients interviewed, patients were aged 23–76 years (median age was 41.5), 64% were female and 173 reported taking a co-medication. Sixty-six (33%) were taking a medication or medications which had no significant drug interaction associated with them. One hundred and seven (54%) were taking one or more medications with a CSDI which could require a dose adjustment, close monitoring or an absolute contraindication. Only 27% of these co-medications were identified in the normal course of an outpatient visit outside of the audit.
A detailed medication history is often lacking at routine HIV follow-up visits. There is a significant risk of CSDIs in this cohort. Awareness of physicians and pharmacists needs to be raised. Implementation of several innovative strategies to capture the most accurate medication histories and avoid drug toxicities now employed in this cohort is also discussed here.
KeywordsCobicistat Cytochrome P450 Drug interaction HIV Ritonavir
PH designed the study, collected and analysed the data and wrote the first draft of the manuscript EdeB, SMcC designed the study and edited the manuscript, RMacC, and DL collected the data. All authors reviewed and approved the final version of the manuscript.
This work was conducted by the infectious diseases team. No additional funding for this work has been received.
Compliance with ethical standardsConflict of interests
The authors declare that they have no conflict of interest.
Beaumont Hospitals’ audit review board deemed the study a review of service provision. All procedures which were performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was requested from all individual participants included in the study.
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