Researchers Warning Of Adverse Drug Interactions In COVID-19 Patients Treated With Paxlovid

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Leading cardiologists and physicians from various hospitals and medical centers across the state of Massachusetts-USA have issued a warning of adverse drug interactions especially involving heart medications in COVID-19 patients treated with Paxlovid (Nirmatrelvir/Ritonavir).

The study review and warning were published in the peer reviewed Journal of the American College of Cardiology.
https://www.sciencedirect.com/science/article/abs/pii/S0735109722068255

Heart disease patients with symptomatic COVID-19 are often treated with nirmatrelvir-ritonavir (Paxlovid) to prevent progression to severe disease; however, it can interact with some previously prescribed medications. A review paper published today in the Journal of the American College of Cardiology examines the potential drug-drug interactions (DDIs) between Paxlovid and commonly used cardiovascular medications, as well as potential options to mitigate severe adverse effects.

“Awareness of the presence of drug-drug interactions of Paxlovid with common cardiovascular drugs is key. System-level interventions by integrating drug-drug interactions into electronic medical records could help avoid related adverse events,” said Sarju Ganatra, MD, director of the cardio-oncology program at Lahey Hospital and Medical Center in Burlington, Massachusetts, and the senior author of the review.

“The prescription of Paxlovid could be incorporated into an order set, which allows physicians, whether it be primary care physicians or cardiology providers, to consciously rule out any contraindications to the co-administration of Paxlovid. Consultation with other members of the health care team, particularly pharmacists, can prove to be extremely valuable. However, a health care provider’s fundamental understanding of the drug-drug interactions with cardiovascular medications is key.”

Paxlovid received emergency use authorization from the U.S. Food and Drug Administration in December 2021 as an oral antiviral agent for the treatment of symptomatic, non-hospitalized adults with mild to moderate COVID-19 infection who are at high risk for progression to severe disease. Patients with heart disease and other risk factors, including diabetes, high blood pressure, chronic kidney disease and smoking make up a large portion of the high-risk population for whom Paxlovid is beneficial.

According to the authors, Paxlovid has been shown to be very effective in patients with existing heart disease, but it has significant DDIs with commonly used cardiovascular medications, highlighting the importance for all clinicians to be familiar with these DDIs. As there is limited clinical information regarding DDI-related adverse events, the authors used existing knowledge and data regarding how therapies like Paxlovid typically react with other medications to provide guidance regarding potential interactions and the associated likely consequences based on the degree of interaction.

The review provides an in-depth overview of a variety of cardiovascular medications used to treat many forms of heart disease. Five of the most important cardiovascular drug interactions with Paxlovid to be aware of include:

  • Antiarrhythmic agents
    • Antiarrhythmic agents are used to manage abnormal heart rhythm. Many of these drugs are metabolized in a way that increases plasma levels when co-administered with Paxlovid. While it may be possible to start Paxlovid after 2-2.5-day temporary discontinuation of the antiarrhythmic agents, this may not be feasible from a practical standpoint. Clinicians are advised to consider alternative COVID-19 therapies and avoid co-administration of these agents with Paxlovid. Sotalol, another antiarrhythmic agent, is renally cleared and does not interact with Paxlovid.
  • Antiplatelet agents and anticoagulants
    • Antiplatelet agents are used for the treatment of coronary artery disease, particularly if a patient has received a stent. Aspirin and prasugrel are safe to co-administer with Paxlovid. There is an increased risk of blood clots when Paxlovid is given alongside clopidogrel and an increased risk of bleeding when given with ticagrelor. When possible, these agents should be switched to prasugrel. If patients have contraindication to taking prasugrel, then co-administration of Paxlovid should be avoided and alternative COVID-19 therapies should be considered.
    • Anticoagulants, or blood thinners used to treat or prevent blood clots, such as warfarin may be co-administered with Paxlovid but require close monitoring of clotting factors in bloodwork. The plasma levels of all direct oral anticoagulants increase when co-administered with Paxlovid, therefore dose adjustment or temporary discontinuation and use of alternative anticoagulants may be required.
  • Certain statins
    • Co-administration of simvastatin or lovastatin with Paxlovid can lead to increased plasma levels and subsequent muscle weakness (myopathy) and rhabdomyolysis, a condition in which the breakdown of muscle tissue releases a damaging protein into the bloodstream. These agents should be stopped prior to initiation of Paxlovid. A dose reduction of atorvastatin and rosuvastatin is reasonable when co-administered with Paxlovid. The other statins are considered safe when given along with Paxlovid.
  • Ranolazine
    • Plasma concentration of ranolazine, used to treat angina and other heart-related chest pain, is exponentially increased in the presence of CPY450 inhibitors like Paxlovid, thereby increasing the risk of clinically significant QT prolongation and torsade de pointes (a type of arrhythmia). Co-administration of Paxlovid is therefore contraindicated. Temporary discontinuation of ranolazine is advised if prescribing Paxlovid.
  • Immunosuppressive agents
    • The plasma levels of immunosuppressive agents prescribed for patients who have undergone heart transplantation exponentially rise to toxic levels when co-administered with Paxlovid. Temporary reduction of dosing of immunosuppressive agents would require frequent monitoring and be logistically difficult. Therefore, alternative COVID-19 therapies should be considered in these patients.

The authors conclude awareness and availability of other COVID-19 therapies enable clinicians to offer alternative treatment options to patients who are unable to take Paxlovid due to DDIs.

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The American College of Cardiology envisions a world where innovation and knowledge optimize cardiovascular care and outcomes. As the professional home for the entire cardiovascular care team, the mission of the College and its more than 56,000 members is to transform cardiovascular care and to improve heart health. The ACC bestows credentials upon cardiovascular professionals who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. The College also provides professional medical education, disseminates cardiovascular research through its world-renowned JACC Journals, operates national registries to measure and improve care, and offers cardiovascular accreditation to hospitals and institutions. For more, visit acc.org

The ACC’s family of JACC Journals rank among the top cardiovascular journals in the world for scientific impact. The flagship journal, the Journal of the American College of Cardiology (JACC) — and family of specialty journals consisting of JACC: Advances, JACC: Asia, JACC: Basic to Translational Science, JACC: CardioOncology, JACC: Cardiovascular ImagingJACC: Cardiovascular InterventionsJACC: Case Reports, JACC: Clinical Electrophysiology and JACC: Heart Failure — pride themselves on publishing the top peer-reviewed research on all aspects of cardiovascular disease. Learn more at JACC.org.

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