January 10, 2022 | Karin Whiting Burgess - School of Pharmacy

What you need to know about Pfizer’s anti COVID-19 drug Paxlovid

Paxlovid can interact with close to 50% of commonly prescribed drugs. Looking carefully at the medications a patient is already taking, and thoughtfully reducing dosages, can help avoid bad reactions.

A rendering of the COVID-19 virus

The FDA has authorized Pfizer’s Paxlovid for emergency use* to treat COVID-19 patients at high risk of hospitalization or death. Paxlovid can slow the replication of the virus that causes COVID, but it has the potential for dangerous interactions with drugs commonly prescribed for diabetes, heart disease, and many other conditions.

High risk patients are often those who have not been vaccinated, and/or have a number of comorbidities (additional, chronic health problems) such as hypertension, diabetes, hyperlipidemia, depression, and cancer.

Patients already taking multiple drugs to control chronic diseases, could be effected by harmful drug interactions between the their current drugs and Paxlovid. Awareness of potential drug-drug interactions may help to avoid severe adverse drug reactions and improve efficacy of Paxlovid’s anti-COVID-19 activity.

Paxloid contains two medicines in two separate tablets, nirmatrelvir and ritonavir. The drug’s anti-COVID-19 activity relies on the inhibition of SARS-CoV-2 Mpro enzyme activity by nirmatrelvir, which results in inhibition of virus replication.  Nirmatrelvir is a substrate of cytochrome P450 CYP3A4 for metabolism.

Ritonavir is an HIV drug that inhibits CYP3A4 and slows the metabolism of Nirmatrelvir, therefore enhancing efficacy of anti-virus activity of Nirmatrelvir.

“Drug-drug interactions are a concern,” says Xiaobo Zhong, Ph.D. Professor of Pharmacology & Toxicology in the Department of Pharmaceutical Sciences at the School of Pharmacy.  “CYP3A4 is responsible for metabolizing 40-50% of current prescription drugs. There are potential drug-drug interactions between (1) Nirmatrelvir and other CYP3A4 substrate drugs in competition to bind to CYP3A4; (2) Ritonavir and other CYP3A4 substrate drugs to increase potential severe adverse reactions; and (3) Nirmatrelvir and other CYP3A4 inducer to decrease efficacy of Paxlovid’s anti-COVID-19 activity.”

Zhong recommends reviewing the Paxlovid Drug-drug Interactions of the NIH COVID-19 Treatment Guideline.

Per the guidelines, an alternative COVID-19 therapy should be considered if any of the listed medications is being taken:  amiodarone, apalutamide, bosentan, carbamazepine, cisapride, clopidogrel, clozapine, colchicine, disopyramide, dofetilide, dronedarone, eplerenone, ergot derivatives, flecainide, flibanserin, glecaprevir/pibrentasvir, iradine, lumateperone, lurasidone, mexiletine, phenobarbital, phenytoin, pimozide, propafenone, quinidine, ranolazine, rifampin, rifapentine, rivaroxaban, sildenafil, St. John’s wort, tadalafil, ticagrelor, and vorapaxar.

The Guideline also indicates that if Paxlovid is prescribed, any of the listed medications should be withheld until completion of Paxlovid, including alfuzosin, alprazolam, atorvastatin, avanafil, clonazepam, codeine, cyclosporine, diazepam, everolimus, fentanyl, hydrocodone, lomitapide, lovastatin, meperidine (pethidine), midazolam (oral), oxycodone, piroxicam, propoxyphene, rosuvastatin, salmeterol, sildenafil, silodosin, simvastatin, sirolimus, suvorexant, tacrolimus, tadalafil, tamsulosin, tramadol, triazolam, and vardenafil.

Drug interactions may be added at any time, so please check the guidelines (link above).

“To avoid potential damage to liver, kidneys and more it is critical that patients fully disclose their medication regimes and prescribers work with pharmacists when prescribing,” says Zhong.

*At the time of this article’s publish date, Paxlovid is considered an investigational drug and is not a fully FDA-approved medication.