Pharmacokinetic enhancers (cobicistat/ritonavir) and the potential for drug-drug interactions

Abstract

Background: 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.

Aims: An audit was conducted to measure and correct for patients exposed to potentially dangerous drug interactions.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Cobicistat; Cytochrome P450; Drug interaction; HIV; Ritonavir.