A case report of a prolonged decrease in tacrolimus clearance due to co-administration of nirmatrelvir/ritonavir in a lung transplant recipient receiving itraconazole prophylaxis.

BACKGROUND: Drug-drug interaction management is complex. Nirmatrelvir/ritonavir is a potent cytochrome P450 (CYP) 3A inhibitor and influences pharmacokinetics of co-administered drugs. Although there are several reports about drug-drug interactions of nirmatrelvir/ritonavir, an influence of a concomitant use of nirmatrelvir/ritonavir and another potent CYP3A inhibitor on tacrolimus remains unclear. Here, we experienced a lung transplant patient with the novel coronavirus disease 2019 (COVID-19). In this patient, nirmatrelvir/ritonavir was administered, and the inhibitory effect of itraconazole on CYP3A was prolonged. CASE PRESENTATION: We present a case in forties who had undergone lung transplantation. He was administered itraconazole and tacrolimus 1.0 mg/d, with a trough value of 8-12 ng/mL. The patient contracted the COVID-19, and a nirmatrelvir/ritonavir treatment was initiated. During the antiviral treatment, tacrolimus administration was discontinued for 5 d. Tacrolimus was resumed at 1.0 mg/d after completion of the nirmatrelvir/ritonavir treatment, but the trough value after 7 d was high at 31.6 ng/mL. Subsequently, the patient was placed on another 36-h tacrolimus discontinuation, but the trough value decreased to only 16.0 ng/mL. CONCLUSIONS: Co-administration of ritonavir caused a prolonged decrease in tacrolimus clearance through its inhibitory effects on CYP3A in a patient taking itraconazole. Management of drug-drug interaction by pharmacists can be important for patients with multiple medications.

Improved absorption of itraconazole tablet by co-administration with lemon beverages in a lung transplant recipient: A case report.

After lung transplantation, itraconazole (ITCZ) is used as a prophylaxis for aspergillosis. ITCZ is a weak base with high lipophilicity, and the dissolution and absorption of ITCZ tablets and capsules are pH dependent. Therefore, ITCZ may not achieve sufficient serum concentrations in patients with higher gastric pH because of its poor bioavailability. We report a case of a woman in fifties with post-COVID-19 respiratory failure who successfully underwent lung transplantation, followed by improved bioavailability of ITCZ tablets when given with acidic lemon beverages. The patient was initially administered ITCZ oral solution; this was discontinued because of its unpleasant taste, nausea, and vomiting. The ITCZ oral solution was replaced with ITCZ tablets 78 days after transplantation; however, serum concentrations of ITCZ and hydroxy-ITCZ were below the detection limit (100 ng/mL). We co-administered ITCZ tablets with commercially available lemon beverages. Subsequently, serum concentrations of ITCZ and hydroxy-ITCZ increased to 341 and 673 ng/mL, respectively, on the 125th day after transplantation. Infection with fungi, including Aspergillus spp., was not observed in this case. The patient had no adverse events such as gastric ulcer or hyperglycemia. These results suggest that the co-administration of lemon beverages and ITCZ tablets may help achieve better absorption of ITCZ in patients taking acid suppressants.