Warning on Paxlovid interactions with immunosuppressive therapy

Clinicians have been reminded that the antiviral agent nirmatrelvir-ritonavir (Paxlovid) used for managing COVID-19 can interact with a number of common immunosuppressive therapies.

According to a review article published in the Journal of the American College of Cardiology [link here], the potential for drug-drug interactions is high and dose adjustment or temporary interruption of medications may be required when prescribing nirmatrelvir-ritonavir (NMVr).

Such adjustments to regular medication may be required for the duration of NMVr treatment and 3-5 days after completion.

Ritonovir, well established in antiretroviral therapy for HIV, appears to be the problematic component as the protease inhibitor variously inhibits cytochrome P (CYP) 450 enzymes which are responsible for metabolising many medications.

The Review stated that immunosuppressive therapies tacrolimus, sirolimus and cyclosporine were contraindicated.

“Co-administration with ritonavir can lead to dangerously increased plasma levels of tacrolimus/cyclosporine,” it said.

For cyclosporine,“frequently prescribed in heart transplant recipients”, it said dose reduction to 80% of total daily dose and consideration of a once daily dosing was one suggested approach.

“However, a substantial reduction in dosing and frequent monitoring of drug levels make the use of NMVr logistically difficult, and NMVr is therefore not recommended in these patients; alternative COVID-19 therapies should be considered.”

Mycophenolate was flagged as having the potential for drug-drug interactions but not contraindicated.

The Review also noted that dexamethasone, methylprednisone and prednisone were potential interactions with the risk of increased drug levels leading to possible Cushing’s syndrome and adrenal suppression.

“The NMVr label recommends switching to prednisolone or beclomethasone, which have less interactions with NMVr,” it said.

Other common medications flagged as cause for concern included the anticoagulant rivaroxaban, a number of statins, most anti-hypertensive drugs and many other cardiovascular drugs.

Senior investigator on the Review and cardiologist Dr Sarju Ganatra said in a statement released by the American College of Cardiology that system-level interventions integrating drug-drug interactions into electronic medical records could help avoid related adverse events.

“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,” he said.

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