#PRAC #February #reminder #adverse #effects #Paxlovid #combination #immunosuppressants
At its February 2024 meeting, the Committee for Pharmacovigilance Risk Assessment of the European Medicines Agency reminded healthcare professionals of the risk of serious and potentially fatal adverse reactions from Paxlovid when used used in combination with certain immunosuppressants.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) reminds healthcare professionals of the risk of serious and potentially fatal adverse reactions Paxlovid (containing the active substances nirmatrelvir and ritonavir) when used in combination with certain immunosuppressants with a fairly narrow safe dosage range (where small changes in dose can lead to serious adverse effects), due to drug interactions reducing the body’s ability to eliminate these drugs.
Paxlovid is a medicine used to treat COVID-19 in adults who do not need supplemental oxygen and are at increased risk of the disease getting worse. The immunosuppressants concerned are calcineurin inhibitors (tacrolimus, cyclosporin) and mTOR inhibitors (everolimus, sirolimus), which reduce the activity of the immune system. They are used to treat certain autoimmune disorders or to prevent the body from rejecting transplanted organs.
Paxlovid should only be administered with tacrolimus, cyclosporin, everolimus or sirolimus if close and regular monitoring of their blood levels is possible, to reduce the risk of drug interactions leading to serious reactions. Healthcare professionals should consult with a multidisciplinary group of specialists to manage the complexity of taking these medications together.
Paxlovid should not be administered in combination with drugs whose elimination from the body depends heavily on a set of liver enzymes (proteins), known as CYP3A, and whose safe dosage range is also narrow. This includes the immunosuppressant called voclosporin. Before initiating treatment with Paxlovid, healthcare professionals should carefully weigh the potential benefits of treatment with Paxlovid against the risks of serious adverse effects if administered concurrently with immunosuppressants.
The PRAC reviewed all available evidence, including reports of serious adverse reactions, some of which were fatal, resulting from drug interactions between Paxlovid and these immunosuppressants. In several cases, blood levels of these immunosuppressants increased rapidly to toxic levels, causing life-threatening conditions. Therefore, the PRAC has 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.
The DHPC for Paxlovid will be forwarded to the EMA Committee for Medicinal Products for Human Use (CHMP). Once adopted, the DHPC will be disseminated to healthcare professionals by the marketing authorization holder, in accordance with an agreed communication plan, and published on the direct communication to healthcare professionals page and in the national registers of EU Member States.
Paxlovid is authorized and marketed in Belgium.
Further information can be found on the EMA website.
