Dr EVAN BROWNE1, Dr VICTORIA SASONGKO1, Dr WILLIAM JAMES1
1Lismore Base Hospital, Lismore, Australia
Biography:
Victoria Sasongko is a staff specialist at Lismore Hospital. Full biography to be supplied closer to date.
Background:
Tacrolimus is metabolised by CYP3A4 and CYP3A5 enzymes and transported by P-glycoprotein. Ritonavir is an irreversible CYP3A4 and p-glycoprotein inhibitor.
Case report:
A 70-year-old female was admitted in the context of COVID-19 and had a background of renal transplant regularly on tacrolimus (prograf) 1mg/1.5mg, mycophenolate 360mg twice-daily and prednisone 2.5mg daily. She liaised with a telehealth doctor who prescribed nirmaltrevir/ritonavir (paxlovid) having taken two doses. The patient had a tacrolimus trough concentration of 6.8microg/L the preceding month. Her admission biochemistry demonstrated a tacrolimus concentration of 51.8microg/L 4 hours post paxlovid. She received a dose of 1.5mg prograf the first evening and 1mg the subsequent morning as she had denied medicine changes upon admission. She had concentrations of 80.5, 59.9, 48.3, and 30.4microg/L at 35, 60, 72 and 95 hours post paxlovid suspension respectively. Her creatinine peaked at 152mmol/L three days into the admission from baseline of 90mmol/L. She had an apparent tacrolimus half-life of 50 hours and 35 hours at the second- and fourth-day post-exposure respectively. Her diarrhoea resolved on day three. She did not demonstrate haemolysis, hypertension or neurotoxicity and recommenced prograf the sixth day.
Conclusions:
Prescribers should be vigilant for drug interactions consulting with the University of Liverpool checker. The metabolite of ritonavir irreversibly binds to CYP3A4 enzyme meaning the mechanistic inhibition generally lasts multiple days after suspension.