Inhibition of repaglinide metabolism by letermovir prolonged severe hypoglycemia in a kidney transplant recipient: A case report and literature review

Background The prevention of cytomegalovirus (CMV) infection after kidney transplantation (KTx) is important. Letermovir (LTV), a drug used for CMV prophylaxis, has various drug–drug interactions. Repaglinide (RPG), an anti-diabetic drug administered after KTx, is a substrate for CYP2C8, which may interact with LTV. We report the first case of a KTx recipient with prolonged severe hypoglycemia due to the enhanced effects of RPG caused by CYP2C8 inhibition by LTV. Case presentation The patient was a woman in 60s who underwent living-donor KTx. RPG (0.5 mg three times a day immediately before each meal) was started on day 27 post-KTx. Although renal function did not improve sufficiently owing to the development of acute tubular necrosis and thrombotic microangiopathy, the patient was weaned off hemodialysis and discharged on day 36 post-KTx (creatinine, 3.57 mg/dL; estimated glomerular filtration rate, 10.8 mL/min/1.73 m ² ). On the day of discharge (day 0), 480 mg LTV was administered once daily for CMV prophylaxis. The patient was brought to the emergency room because she lost consciousness at home at approximately 4 PM on day 2. The blood glucose level (BGL) at the time of transport was 33 mg/dL, indicating severe hypoglycemia. Therefore, RPG was discontinued immediately before lunch on day 2, and 40 mL of 50% glucose was administered. After transportation, 500 mL of 10% glucose was administered intravenously in parallel. However, the BGL decreased to 32 mg/dL at 9 PM. Hypoglycemia caused by short-acting RPGs usually does not persist for several hours. We considered the possibility of prolonged severe hypoglycemia due to the interaction of LTV and RPG, and LTV was suspended on day 3. No hypoglycemia occurred after 9 AM on day 3. LTV administration was resumed on day 6, and the patient was discharged on day 7 without further hypoglycemic events. Conclusions Delayed elimination owing to severe renal dysfunction and CYP2C8 inhibition by LTV potentiated the effects of RPG and caused prolonged severe hypoglycemia. When LTV is used for CMV prophylaxis in KTx patients, close attention should be paid to interactions with non-immunosuppressive drugs.