COVID drug Paxlovid interacts with widely used CV drugs: review

The antiviral treatment, which combines nirmatrelvir and ritonavir (Paxlovid; Pfizer), while effective in patients with mild to moderate COVID-19, may interact with many commonly prescribed cardiovascular drugs, researchers point out in a review in the Journal of the American College of Cardiology.

The main culprit is ritonavir, which was first approved for the treatment of HIV in 1996 and affects both the CYP450 signaling pathway involved in the metabolism of many drugs and the P-glycoprotein pump involved in drug transport.

“The clinical community should be aware that there is a potential for serious interactions when Paxlovid is prescribed to people taking cardiovascular medications,” Sarju Ganatra, MD (Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington , MA), senior author of the review, TCTMD said. “However, this is not a reason to discourage people from prescribing Paxlovid.”

The paper includes a table and figure listing dozens of CV drugs and whether Paxlovid is safe to use in combination, whether some sort of adjustment or temporary suspension of CV drugs is required before antiviral therapy is used, or whether Paxlovid this shouldn’t be used at all. The central figure contains an algorithm that guides clinicians through this decision-making process.

“In most cases, our attempt has been that if it is practical, we would propose a route whereby patients receive treatment with Paxlovid when a change in the drug itself is required – whether it is the dose maintain or reduce,” said Ganatra.

However, this is not always possible, particularly when patients are taking a CV drug with a long half-life, he noted. The antiarrhythmic drug amiodarone, for example, has a very long half-life, and even if it were interrupted, it would remain in the system long enough to make Paxlovid treatment impractical. “In these scenarios, we have proposed an alternative treatment for COVID-19 that I believe is important to clinicians and patients alike – that sometimes holding a drug by itself is not enough to avoid interactions,” he explained.

The clinical community should be aware of the potential for serious drug interactions when prescribing Paxlovid to patients taking cardiovascular medications. Saryu Ganatra

Paxlovid has been an exciting development in the response to the pandemic, Ganatra said. In which EPIC HR Study shown to reduce risk of hospitalization or death by day 28 by 89% in non-hospitalized, unvaccinated, high-risk COVID-19 adults. The U.S. Food and Drug Administration approved the combination therapy in December 2021 for emergency use, with an indication for unhospitalized patients 12 years and older with mild to moderate COVID-19 and at high risk of progression to severe disease.

Patients with cardiovascular disease and cardiovascular risk factors were well represented among high-risk patients and benefited even more than the overall study cohort. But many of these patients are taking medications that can interact with Paxlovid in potentially harmful ways.

Much of this is due to ingestion of ritonavir, which has been added to nirmatrelvir to slow down liver metabolism and increase the time it is allowed to act in the body. Ritonavir inhibits enzymes of the CYP450 signaling pathway, mainly CYP3A4 but also CYP2D6. These enzymes are involved in the metabolism of many drugs, including many drugs used by patients with cardiovascular disease.

A FDA data sheet on Paxlovid for Healthcare Providers details potential drug interactions that can lead to serious or life-threatening reactions, but the review in JACCwith lead author Sonu Abraham, MD (Lahey Hospital and Medical Center, Beth Israel Lahey Health), focuses on drugs used in various cardiovascular diseases.

Some of the interaction information is based on clinical data from the use of ritonavir in HIV over the past few decades, while other is based on what is known about the pharmacokinetics and pharmacodynamics of the drugs.

To simplify the information, the authors provide a figure of 80 drugs from several categories: antiplatelet/anticoagulant drugs, lipid-lowering drugs, antianginics, antihypertensives, antiarrhythmics, heart failure therapies, pulmonary hypertension therapies, immunosuppressants, and anti-inflammatory drugs. Those that can be safely co-administered with Paxlovid receive a blue dot (36 drugs), those with a potential interaction requiring dose adjustment or temporary discontinuation receive an orange dot (34 drugs), and those not co-administered with Paxlovid should be used receive a gray dot (20 drugs).

Ganatra highlighted antiplatelet/anticoagulant drugs, antiarrhythmic drugs and certain statins as major concerns when it comes to drug interactions with Paxlovid due to the drugs’ widespread use. However, most interactions and serious outcomes — which can include increased bleeding, life-threatening arrhythmias, myopathies or liver toxicity — can be avoided by either stopping or reducing the dose of these drugs, he said. “So there is a way, and still people with Paxlovid can get the COVID-19 treatment they want.”

Immunosuppressive drugs used in heart transplant recipients are not as commonly prescribed, but potential interactions with Paxlovid that result in toxic drug levels are of particular concern given the patients’ illness, Ganatra said.

“The importance of medication matching prior to initiating nirmatrelvir/ritonavir treatment to avoid serious drug-drug interactions cannot be overemphasized,” the authors write.

Ganatra pointed out that hospitals and healthcare systems are able to address this issue by making adjustments to their electronic medical record systems. Built-in algorithms, he noted, can warn prescribers of possible interactions and offer possible solutions.