Calcium-Channel Blocker–Clarithromycin Drug Interactions and Acute Kidney Injury
Why this work is in the frame
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Bibliographic record
Abstract
IMPORTANCE: Calcium-channel blockers are metabolized by the cytochrome P450 3A4 (CYP3A4; EC 1.14.13.97) enzyme. Blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor of CYP3A4 and azithromycin is not, which makes comparisons between these 2 macrolide antibiotics useful in assessing clinically important drug interactions. OBJECTIVE: To characterize the risk of acute adverse events following coprescription of clarithromycin compared with azithromycin in older adults taking a calcium-channel blocker. DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study in Ontario, Canada, from 2003 through 2012 of older adults (mean age, 76 years) who were newly coprescribed clarithromycin (n = 96,226) or azithromycin (n = 94,083) while taking a calcium-channel blocker (amlodipine, felodipine, nifedipine, diltiazem, or verapamil). MAIN OUTCOMES AND MEASURES: Hospitalization with acute kidney injury (primary outcome) and hospitalization with hypotension and all-cause mortality (secondary outcomes examined separately). Outcomes were assessed within 30 days of a new coprescription. RESULTS: There were no differences in measured baseline characteristics between the clarithromycin and azithromycin groups. Amlodipine was the most commonly prescribed calcium-channel blocker (more than 50% of patients). Coprescribing clarithromycin vs azithromycin with a calcium-channel blocker was associated with a higher risk of hospitalization with acute kidney injury (420 patients of 96,226 taking clarithromycin [0.44%] vs 208 patients of 94,083 taking azithromycin [0.22%]; absolute risk increase, 0.22% [95% CI, 0.16%-0.27%]; odds ratio [OR], 1.98 [95% CI, 1.68-2.34]). In a subgroup analysis, the risk was highest with dihydropyridines, particularly nifedipine (OR, 5.33 [95% CI, 3.39-8.38]; absolute risk increase, 0.63% [95% CI, 0.49%-0.78%]). Coprescription with clarithromycin was also associated with a higher risk of hospitalization with hypotension (111 patients of 96,226 taking clarithromycin [0.12%] vs 68 patients of 94,083 taking azithromycin [0.07%]; absolute risk increase, 0.04% [95% CI, 0.02%-0.07%]; OR, 1.60 [95% CI, 1.18-2.16]) and all-cause mortality (984 patients of 96,226 taking clarithromycin [1.02%] vs 555 patients of 94,083 taking azithromycin [0.59%]; absolute risk increase, 0.43% [95% CI, 0.35%-0.51%]; OR, 1.74 [95% CI, 1.57-1.93]). CONCLUSIONS AND RELEVANCE: Among older adults taking a calcium-channel blocker, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically significant greater 30-day risk of hospitalization with acute kidney injury. These findings support current safety warnings regarding concurrent use of CYP3A4 inhibitors and calcium-channel blockers.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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