RWE-001 - USING REAL WORLD EVIDENCE (RWE) TO ASSESS DRUG-DRUG INTERACTION (DDI) BETWEEN PAXLOVID AND THE TOP 100 PRESCRIBED DRUGS IN THE US.

J. Gerhart¹, F. Draica², M. Benigno², G. Sidhu², J. Atkinson³, M. Reimbaeva⁴, D. Francis², N. Baillon-Plot⁵, B. Damle²; ¹Pfizer, Collegeville, PA, USA, ²Pfizer, New York, NY, USA, ³Pfizer, Walton Oaks, Tadworth, United Kingdom, ⁴Pfizer, Groton, CT, USA, ⁵Pfizer, Paris, France.

Background: PAXLOVIDTM (nirmatrelvir/ritonavir) has received a US EUA for patients ≥12 years with mild-to-moderate COVID-19 at high-risk of progression to severe disease. DDI studies conducted with PAXLOVID implicate the PK enhancer ritonavir as the main perpetrator of DDIs. Ritonavir is a potent inhibitor of CYP3A4, CYP2D6, and P-gp. The PAXLOVID Fact Sheet1 identifies contraindicated drugs and those with a potentially important interaction.

Methods: A retrospective analysis was conducted using RWE from the Optum Clinformatics Data Mart. Patients were identified based on CDC criteria for high-risk COVID-19 and confirmed continuous insurance enrollment from Jan 1 to Dec 31, 2019 with ≥1 prescription claim. Excluding non-drug claims (e.g., vaccines), the top 100 drugs were selected and ranked based on total patient counts. DDI potential with PAXLOVID was evaluated using US Prescribing and DailyMed Information or relevant literature for each drug.

Results: Of the top 100, 70 drugs are not expected to have a DDI with PAXLOVID. These drugs are eliminated unchanged in urine, cleared by enzymes other than CYP3A4 or CYP2D6, are not P-gp substrates, or are cleared by multiple pathways. The remaining 30 drugs expected to have a DDI are represented in the PAXLOVID Fact Sheet. The top four drug classes expected to interact with PAXLOVID include corticosteroids, narcotic analgesics, anticoagulants, and statins. One drug, simvastatin, is contraindicated. The mechanism of interaction with PAXLOVID, or lack thereof, will be presented in detail for each drug.

Conclusion: PAXLOVID DDI management is important to ensure the right patients receive this antiviral. This analysis provides an understanding of PAXLOVID interactions with the top 100 drugs likely to be used in high-risk COVID-19 patients and serves as an additional DDI management resource.

PAXLOVID (nirmatrelvir tablets; ritonavir tablets). US Prescribing Information (USPI). Pfizer, Inc. https://www.fda.gov/media/155050/download (2022). Accessed 09 Sep 2022.