EMA’s safety committee (PRAC) is reminding healthcare professionals of the risk of serious and potentially fatal adverse reactions with Paxlovid when used in combination with certain immunosuppressants that have a narrow safe dosage range (where small changes in the dose can lead to serious adverse reactions), due to drug-drug interactions reducing the body’s ability to eliminate these medicines. The PRAC reviewed all available evidence, including reports of serious adverse reactions, some of which were fatal, resulting from drug-drug interactions between Paxlovid and these immunosuppressants. In several cases, blood levels of these immunosuppressants increased rapidly to toxic levels resulting in life-threatening conditions. Therefore, the PRAC agreed on a direct healthcare professional communication (DHPC) to remind healthcare professionals of the risk of these interactions, which is known and already described in the product information for this medicine.
Paxlovid is a medicine used for treating COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of the disease becoming severe. The immunosuppressants concerned are called calcineurin inhibitors (tacrolimus, ciclosporin) and mTOR inhibitors (everolimus, sirolimus), which reduce the activity of the immune system. They are used for treating certain autoimmune disorders or for preventing the body from rejecting transplanted organs.
Paxlovid should only be given with tacrolimus, ciclosporin, everolimus or sirolimus if close and regular monitoring of their blood levels is possible, to reduce the risk of drug-drug interactions causing serious reactions. Healthcare professionals need to consult with a multidisciplinary group of specialists to manage the complexity of taking these medicines together. Paxlovid must not be given in combination with medicines for which elimination from the body is highly reliant on a set of liver enzymes (proteins), known as CYP3A, and that also have a narrow safe dosage range. This includes the immunosuppressant called voclosporin.
Before starting the treatment with Paxlovid, healthcare professionals should carefully weigh the potential benefits of Paxlovid treatment against the risks of serious adverse reactions in case of administration together with immunosuppressants.
Learn more at: https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-5-8-february-2024
