Evaluation of a Protocol Managing the Cyclosporine and Nirmatrelvir/Ritonavir Interaction in Kidney Transplant Recipients
Bibliographic record
Abstract
Key Points This is the first protocol managing this drug interaction with documented patient follow-up data. The protocol, applied empirically, was able to restore cyclosporine levels within 9 days of the drug interaction. There were no significant and negative patient safety outcomes associated with the application of the protocol. Background Nirmatrelvir/ritonavir (NRMr) has emerged as a crucial treatment for managing coronavirus disease 2019 (COVID-19) infections but interacts with calcineurin inhibitors. This study aims to assess the application of a standardized protocol managing this drug–drug interaction, specifically with cyclosporine, because current evidence is limited. Methods This retrospective study included recipients on cyclosporine undergoing therapy with NRMr between April 2022 and December 2023. As per protocol, cyclosporine doses were reduced by 80%, and levels were measured 2 days after course completion. For subtherapeutic or therapeutic levels, cyclosporine dose was reinstated at 100%, with cyclosporine levels reassessed 1 week later. For supratherapeutic levels, the reduced dosage was maintained for an additional 2 days before being reinitiated at 100% of the baseline cyclosporine dose. Protocol adherence and clinical parameters such as cyclosporine levels, AKI episodes, hospitalization, and mortality were monitored up to 30 days after completion of NRMr therapy. Results Thirty-five kidney transplant recipients met eligibility criteria. At baseline, 83% of recipients had therapeutic cyclosporine levels. At the first follow-up 2 days after completion of NRMr, there was a greater proportion of recipients with subtherapeutic and supratherapeutic levels compared with baseline (20% versus 9% and 31% versus 9%), which had improved by the second follow-up at 9 days after completion of NRMr (14% and 14%). Three recipients experienced AKI for reasons unrelated to COVID-19 treatment. There were four hospitalizations, none related to COVID-19 treatment. There was no graft rejection or death 30 days after completion of NRMr. Conclusions Although cyclosporine levels outside therapeutic range were common immediately after completion of NRMr treatment, levels were restored rapidly. No clinically relevant safety events occurred within the 30 days. Adherence to the protocol is crucial when using NRMr in kidney transplant recipients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.013 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".