Tutorial presented by Rhys Oakley, Pharmacist in Cardiff and Vale University Health Board.

In this tutorial, Rhys introduces Paxlovid, a new oral antiviral medication for the treatment of COVID-19, for individuals who are at high risk of progression to severe disease. We discuss the following topics:

1. What is Paxlovid and what is the evidence behind its use?
2. Who is eligible?
3. Other practicalities

Paxlovid contains two antiviral agents, which are co-packaged but not co-formulated; Nirmatrelvir and Ritonavir. Nirmatrelvir is a protease inhibitor, halting the replication of SARS-CoV-2. Ritonavir is a pharmacokinetic enhancer and has no activity against the virus, but acts to increase the concentration of Nirmatrelvir in the plasma.

Paxlovid was approved for use following the Evaluation for Protease Inhibition for COVID-19 in High Risk Patients (EPIC-HR), which was a randomised, double-blind, placebo controlled trial. Patients recruited included those with laboratory confirmed COVID-19, who were symptomatic, symptom onset within 5-days, non-hospitalised, and at least one risk factor for severe disease. It excluded individuals with a prior diagnosis of COVID-19, or anyone who was vaccinated.

Findings were as follows:

There were no deaths in the Paxlovid arm of the treatment trail, compared to 12 deaths in the Placebo arm.

The eligibility for Paxlovid is defined in the Interim Clinical Commissioning Policy (effect from 10/02/2022), linked below, and includes patients with hospital-onset COVID-19 and those with COVID-19 in the community. Patients must test positive for COVID-19 (via lateral flow or PCR), have symptoms, and fall in the high risk category for severe disease. Treatment should be initiated within 5-days of symptom onset, but can be considered up to 7-days (off label use). Treatment will be initiated by hospital teams for those admitted, whereas the National Antiviral Service will send treatment directly to patients in the community, if Paxlovid is the most suitable treatment for them.

Patients with certain hepatic impairments or renal impairments are contraindicated for Paxlovid, including those with Child-Pugh C cirrhosis, and those with severe renal impairment (eGFR<30).

There is a high likelihood of drug-drug interactions, mainly associated with Ritonavir which is a potent CYP3A4 inhibitor and CYP2D6 inhibitor. An accurate medication history should be taken, and the Liverpool Drug Interaction Checker should be used to check interactions. Pharmacists will also be well placed to advise on drug-drug interactions.