Some anti-flammatories don't mix with Paxlovid, according to new in-depth guidance on prescribing for cardiovascular patients.
Clinicians prescribing the covid treatment nirmatrelvir/ritonavir (NVMr) are warned to be aware of its potentially serious drug interactions with a range of commonly used anti-inflammatories, steroids and cardiovascular medications.
This included dexamethasone, methylprednisolone, prednisolone and prednisone.
“Dexamethasone is a CYP3A4 substrate,” the authors wrote in the Journal of the American College of Cardiology (JACC).
“Coadministration of azoles could potentially lead to Cushing’s syndrome and adrenal insufficiency. Expecting similar effects with NVMr, it is suggested to reduce the dose to 50% while taking NVMr and to resume full dose of dexamethasone 3 days after completion of NVMr.”
Methylprednisone and prednisone show similar effects, the authors said.
“The NMVr label recommends switching to prednisolone or beclomethasone, which have less interactions with NMVr. Overall, the incidence of side-effects such as Cushing’s syndrome is relatively low with a short duration of NMVr.”
The authors said many patients with heart disease and symptomatic covid were often treated with nirmatrelvir/ritonavir (Paxlovid, Pfizer Australia) to prevent progression to severe disease.
However, the antiviral can interact with a range of prescribed medications, including some antiplatelets/anticoagulants, certain statins, anti-anginals, antihypertensives, antiarrhythmics, heart failure therapy, pulmonary hypertension therapy, immunosuppressives anti-inflammatories. Not all drugs in these classes have interactions with the antiviral, the researchers reported.
The JACC review paper examines in-depth the potential drug-drug interactions (DDIs) between Paxlovid and about 80 commonly used cardiovascular medications, as well as potential options to mitigate severe adverse effects, including temporary adjustment or interruption of the medication before use of the antiviral therapy, or whether it should be avoided.
US-based senior author on the paper, Dr Sarju Ganatra, said awareness of the potential for DDIs was vital.
“We have described the many known and potential DDIs between various cardiovascular medications and NMVr [Paxlovid],” he said.
“The importance of medication reconciliation before initiation of NMVr cannot be overemphasised to avoid serious DDIs. Dose adjustment or discontinuation of cardiovascular medications may be required for the duration of NMVr treatment and three to five days after completion.”
Dr Ganatra, director of the cardio-oncology program at Lahey Hospital and Medical Centre in Burlington, Massachusetts, said if co-administration of NVMr with certain cardiovascular medications was not advisable or if their temporary discontinuation was impractical, Paxlovid should be avoided and other treatments used.
“Awareness and availability of other covid-19 therapies such as remdesivir, molnupiravir, and anti-SARS-COV-2 monoclonal antibodies enables clinicians to offer alternative treatment options to patients who are unable to take NMVr due to DDIs,” he said.
Statins were among the drug interactions they reviewed. The authors said co-administration of simvastatin or lovastatin with nirmatrelvir/ritonavir could 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,” the authors said in a statement accompanying the paper.
“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.”
The use of immunosuppressive agents in combination with Paxlovid was also a red flag.
“The plasma levels of immunosuppressive agents prescribed for patients who have undergone heart transplantation exponentially rise to toxic levels when co-administered with Paxlovid,” the statement said.
“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.”
While this detailed paper focuses on medications used in treating cardiovascular diseases, there are other potential drug-drug interactions that clinicians should also be aware of before prescribing Paxlovid. In Australia, NPS MedicineWise provides a list of the potential drug interactions.
Journal of the American College of Cardiology 2022, online 12 October
