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Early Clinical Experience with Nirmatrelvir/Ritonavir for Treatment of COVID-19 in Solid Organ Transplant Recipients
American Journal of Transplantation ; 22(Supplement 3):602, 2022.
Article in English | EMBASE | ID: covidwho-2063386
ABSTRACT

Purpose:

Nirmatrelvir/ritonavir use has not yet been described in solid organ transplant recipients (SOTR) who become infected with COVID-19. The objective of our study was to evaluate outcomes among a heterogeneous population of SOTR and quantify the drug-drug interaction with commonly used immunosuppressive medications. Method(s) This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor or mammalian target of rapamycin inhibitor who were prescribed nirmatrelvir/ritonavir between 12/28/21 and 1/6/2022. Result(s) A total of 26 adult SOTR were included (n=20 tacrolimus, n=4 cyclosporine, n=3 everolimus, n=1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of nirmatrelvir/ritonavir hold tacrolimus, reduce cyclosporine dose to 20% of baseline daily dose, and/or hold everolimus/sirolimus. Two patients (7.7%) were hospitalized;one patient for symptoms related to COVID-19 and the other for infectious diarrhea. No patients died within 12 days of receipt of nirmatrelvir/ritonavir. Median time to first CNI trough from completion of nirmatrelvir/ritonavir was 2 days (IQR, 1 - 3). Median tacrolimus trough concentration pre- and post-nirmatrelvir/ritonavir were 7.7 ng/mL (IQR, 6.6 - 8.6) and 5.3 ng/mL (IQR, 3.6 - 8.5), respectively. One patient on cyclosporine had trough concentrations pre- and post- nirmatrelvir/ritonavir of 73 ng/mL and 45 ng/ mL (day 9), while the other patient had a trough of 75.9 ng/mL prior and 190 ng/mL and 80 ng/mL on days 6 and 9, respectively. Median everolimus trough concentration prior to receipt of nirmatrelvir/ritonavir was 4.8 ng/mL (IQR, 3 - 4.9). Everolimus trough concentrations post-nirmatrelvir/ritonavir were undetectable in two patients on day 7 and day 9, and 1.4 ng/mL on day 8 in the third patient. Conclusion(s) Our results suggest that nirmatrelvir/ritonavir may be an effective therapy to prevent COVID-19-related hospitalization and death in SOTR. Furthermore, the clinically significant interaction between nirmatrelvir/ritonavir and immunosuppressive agents can be reasonably managed with a standardized dosing protocol.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: American Journal of Transplantation Year: 2022 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: American Journal of Transplantation Year: 2022 Document Type: Article