Background and importance Management of immunosuppression in recipients of solid organ transplantation (SOT) is challenging. Drugs used in COVID-19 involve drug–drug interactions (DDIs) with immunosuppressants.

Aim and objectives To describe DDIs in hospitalised SOT recipients (SOTr) and to analyse DDI management and their clinical impact.

Material and methods A retrospective single centre study was conducted in SOTr with COVID-19 hospitalised from 11 March to 25 April. Clinical data and pharmacotherapy were recorded from admission up to 28 days or discharge. Lexicomp was used to detect and categorise DDIs according to: risk level (X: avoid combination; D: consider therapy modification; C: monitor therapy; B: no action needed), reliability rating and severity. 46 patients were included: 33 (71.7%) men, aged 62.7±12.6 (mean±SD) years. They had received kidney (30; 56.2%), lung (13; 28.3%) or liver (3; 6.5%) transplants.

Results Immunosuppression at admission: tacrolimus (41; 89.1%), mycophenolate mofetil/mycophenolate sodium (28; 60.9%), prednisone (39; 84.8%), everolimus (7; 15.2%), sirolimus (7; 15.2%) and cyclosporine (1; 2.2%). 106 DDIs affecting 42 (91.3%) patients were detected (patients could have >1 DDI). DDIs were classified as confirmed (18; 39.1%) or potential (33; 71.7%). Immunosuppressants with DDIs: tacrolimus (65; 61.3%), everolimus (12; 11.3%), sirolimus (6; 5.7%), methylprednisolone (12; 11.3%), prednisone (10; 9.4%) and mycophenolate (1; 0.9%).

Drugs for COVID-19 with DDIs: lopinavir/ritonavir (45; 42.5%), azithromycin (32; 30.2%), tocilizumab (15; 14.2%), darunavir/cobicistat (10; 9.4%), and hydroxychloroquine (4; 3.8%). DDIs were risk X (6; 5.6%), risk D (42; 40.8%), risk C (57; 53.7%) and risk B (1; 0.9%). The reliability rate of DDIs was excellent (0.9%), good (52.8%) and fair (44.3%). Severity was low, moderate and major in 6.6%, 84.9% and 8.5% of cases, respectively.

Immunosuppression was withheld in 33 (71.7%) patients due to DDIs. 36 (87.7%) of 41 patients receiving tacrolimus had 65 DDIs; tacrolimus was withdrawn in 22 (61.1%), reduced in 18 (50%) and increased in 4 (11.1%) cases. Seven patients receiving everolimus had 12 DDIs and 4 patients with sirolimus had 6 DDIs; immunosuppressant was stopped in all cases. Tacrolimus levels were supratherapeutic (>10 ng/mL) in 8 (25%) patients at admission, 13 (43.3%; n=30) at 48 hours, 10 (31.3%, n=32) at 7 days and 2 at 14 days (17.7%, n=28). No graft rejection was detected. Mean creatinine serum concentration was 2.2 mg/dL at admission and 2.6 mg/dL 7 days later. Two cases of acute kidney failure were attributable to tacrolimus intoxication.

Conclusion and relevance DDIs were highly prevalent in hospitalised SOTr with COVID-19. Pharmaceutical care is critical to promptly detect and manage DDIs in SOTr.

References and/or acknowledgements Thanks to the COVID-19 Vall d’Hebron Working Group

Conflict of interest No conflict of interest