Adverse reactions to Paxlovid® include changes in taste, diarrhea, hypertension, and muscle pain. Reactions to Lagevrio® include diarrhea, nausea, and dizziness. This list of adverse reactions was developed from limited data and may increase over time.
For Paxlovid® to inhibit SARS-Cov-2 it must be initiated within five days of the onset of Covid-19 symptoms, so modifications to the patient’s normal drug regiment is difficult. Furthermore, interactions with commonly used EMS medications can easily occur. Paxlovid® is a two-component drug. The active SARS related antiviral is nirmatrelvir. The HIV drug ritonavir is added to slow the metabolism of the nirmatrelvir, keeping it metabolically available for a longer treatment period. The ritonavir irreversibly inhibits metabolism for several days. Unfortunately, the ritonavir also enhances the pharmacologic effect of several drugs used in EMS care.
During a time when hundreds of millions have had Covid it is easy to become complacent about that fact, but we must always ascertain a detailed history. In the context of Paxlovid®, the medications amiodarone, diazepam, midazolam (PO), and meperidine are contraindicated. Immune suppressants taken by transplant patients are also absolute contraindications, as are many steroids.
Relevant contraindications include ketamine, fentanyl, morphine, midazolam (IV), and diltiazem. The ritonavir will increase the potency of most pain relievers by a factor of four. The University of Liverpool
maintains a database of potential drug interactions with Paxlovid®. The website lists 48 drugs that should not be used while the patient is taking Paxlovid®. Also listed are 180 additional medications that have potential for interaction.
If your patient’s regular medication regiment includes the use of Eliquis®, Xarelto®, and Plavix®, while being treated with Paxlovid®, your care of the patient should include a vigilant awareness when the patient has potentially experienced a stroke or a head injury, as bleeding would occur more easily. Patients taking warfarin may experience more or less anti-coagulant effects if administered Paxlovid®. Transport of this patient may be required without regard to Covid-19 issues, as the management of any interaction will be complex, with ongoing evaluation of the patient’s INR. Alternatively, a patient may require close monitoring within a community paramedic program, if available, with regular blood draws for a patient that cannot meet outpatient lab requirements during medication with Paxlovid®.
Lagevrio® (molnupiravir) disrupts the SARS-Cov-2 RNA by causing defective replication of the virus, causing it to become noninfectious. There are no drug interactions reported with the use of Lagevrio® but it is not recommended for use during pregnancy. The potential for embryo-fetal toxicity is specific enough that males should counseled regarding potential reproduction during the treatment period.
With the availability of these medications for out of hospital use, EMS personnel will potentially see more patients that are severely ill, even with the tapering down of the virus in most areas. Be vigilant in your personal protection, as the increase in patient severity could increase transmission potential of the virus, given that we do not know when these disruptive medications have become effective in any given patient.
It is important to know the side effects and interaction potential of these medications, as some of those interactions could be life-threatening. You can always contact your medical direction prior to administering anything that you believe questionable concerning these anti-viral medications.
Knowing that your patient is taking either of these medications, and understanding them better, will allow more effective assessment and treatment by EMS responders.
FDA Fact Sheets for Healthcare Providers is available at:
References upon request