Drug Interactions between nirmatrelvir / ritonavir and selpercatinib

Ritonavir may significantly increase the blood levels of selpercatinib. High levels of selpercatinib can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a relatively rare side effect. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). The risk and/or severity of other side effects may also increase, including nausea, vomiting, constipation, diarrhea, rash, muscle and joint pain, swelling of arms or legs, liver problems, high blood pressure, and bleeding complications. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with selpercatinib. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with selpercatinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. The proposed mechanism is decreased clearance in the intestine, kidney, and/or liver due to inhibition of P-gp-mediated efflux by selpercatinib. In vitro studies indicate that selpercatinib inhibits P-gp at clinically relevant concentrations; however, data from clinical studies are lacking.

MANAGEMENT: Caution is advised when selpercatinib is used concurrently with drugs that are P-gp substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever selpercatinib is added to or withdrawn from therapy.