NAPLEX Question of the Week: Paxlovid Drug Interactions

Paxlovid is a newly authorized agent for the treatment of COVID-19. Are you up to date on potential drug interactions associated with this new (yet old in some ways) therapy?
NAPLEX Question of the Week: Paxlovid Drug Interactions

A 65 year old female with a past medical history of morbid obesity (BMI 40), hypertension, atrial fibrillation, hyperlipidemia, and chronic angina reports to her PCM with new fever (Tmax of 101 F earlier this AM), sore throat, body aches, and headaches. Due to prevalence of SARS-CoV-2 in the area, she is tested which confirmed COVID-19. Her current medications are simvastatin 40mg at bedtime, warfarin 7.5mg daily except 5mg on Sundays, lisinopril 40mg once daily, amlodipine 5mg once daily, and ranolazine 500mg BID. Her vital signs are stable but the PCM wishes to place her on Paxlovid. Which of the following medications that our patient takes may accumulate while on Paxlovid and would be contraindicated? Select all that apply. 

A. Warfarin

B. Ranolazine

C. Lisinopril

D. Amlodipine

E. Simvastatin

Answer with rationale:

The correct answers are B and E. Paxlovid is a combination of two separate medications: nirmaltrelvir and ritonavir. While nirmatrelvir is a novel protease inhibitor targeted against SARS-CoV-2, ritonavir is a well known "booster" used for years in the management of HIV in combination with other HIV protease inhibitors, such as atazanavir. Ritonavir similarly is used to boost nirmatrelvir to provide therapeutic concentrations. Ritonavir is a strong CYP 3A4 inhibitor and therefore is associated with frequent drug interactions. Pharmacists must be up-to-date on this agent as it is likely to be used often in the management of mild-moderate COVID-19 to prevent hospitalizations and death in outpatients at high risk for progression to these bad outcomes. 

Ranolazine and simvastatin according to the FDA fact sheet are contraindicated with Paxlovid therapy due to potential accumulation and toxicity of these agents. Answer A is incorrect as warfarin may be continued with Paxlovid just with enhanced INR monitoring. Xarelto (rivaroxaban) while not absolutely contraindicated is not recommended for coadministration per the Emergency Use Authorization (EUA) FDA fact sheet. Answer C (lisinopril) is not expected to have a drug interaction with Paxlovid. Answer D (amlodipine) may accumulate in presence of Paxlovid but is not contraindicated. More frequent monitoring and/or dose adjustment of amlodipine can be considered while on Paxlovid therapy. 

A link to the Paxlovid EUA fact sheet can be found here with more details on a number of other potential drug interactions:

See everyone next week!

Dr. B 

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