Amiodarone–sirolimus/tacrolimus interaction in a pediatric heart transplant patient
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Bibliographic record
Abstract
A two year-old female who had underwent ABO-incompatible heart transplantation at four months of age was admitted with unexplained anemia and renal dysfunction. The patient also had evidence of moderate liver dysfunction. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and prednisolone. Tacrolimus was held on day 2 for five days because of an elevated trough blood concentration. The patient required one fourth of her maintenance dose to keep trough concentrations within the target range. Nadolol and amiodarone were prescribed on day 7 to control ventricular arrhythmias. Sirolimus was prescribed on day 11. A precautionary (non-steady-state) sirolimus trough concentration was grossly elevated. Sirolimus was held and tacrolimus was discontinued. Sirolimus blood concentrations remained above the target range for fourteen days despite successive dose manipulations. The patient succumbed from complications of ECMO on day 42. Amiodarone and cyclosporine interactions in the solid organ transplant population have been previously described. To our knowledge, there are no cases of amiodarone and sirolimus or tacrolimus interactions reported in English literature. Both tacrolimus and sirolimus are metabolized through the same enzyme system as cyclosporine, and the chance of a similar interaction occurring is high. Sirolimus is also a substrate of p-glycoprotein and thus may be significantly affected by amiodarone. We have described a potential interaction with sirolimus, tacrolimus and amiodarone. If amiodarone is deemed the most appropriate choice for the patient, clinicians should consider prospectively decreasing sirolimus and tacrolimus doses. Blood concentrations should also be monitored more frequently in order to minimize prolonged periods of supratherapeutic concentrations and related toxicities.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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 it