Drug-drug interactions of ritonavir-boosted SARS-CoV-2 protease inhibitors in solid organ transplant recipients: experience from the initial use of lopinavir-ritonavir.
Clin Microbiol Infect
; 29(5): 655.e1-655.e4, 2023 May.
Article
in English
| MEDLINE | ID: covidwho-2177749
ABSTRACT
OBJECTIVES:
To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy.METHODS:
Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C0- approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection.RESULTS:
The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed.DISCUSSION:
We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Organ Transplantation
/
COVID-19
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Clin Microbiol Infect
Journal subject:
Communicable Diseases
/
Microbiology
Year:
2023
Document Type:
Article
Affiliation country:
J.cmi.2023.01.002
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