CCB-Clarithromycin Drug Interaction and Risk of Nonvertebral Fracture
the MPR take:
Previous research has suggested that older adults on calcium channel blockers (CCBs) who are co-prescribed clarithromycin experience a greater risk of hospitalization for hypotension within the first 30 days of antibiotic use, and that there is an increased rate of falls and fragility fractures after initiating antihypertensive medications in elderly patients. Can this potential drug-drug interaction lead to a greater risk of nonvertebral fractures secondary to hypotension? A population-level retrospective cohort study from 2003–2012 of older adults (mean age=76 years) assessed CCB use, newly prescribed clarithromycin or azithromycin, and risk of nonvertebral fracture within 30 days of the new coprescription. Amlodipine was the most commonly prescribed CCB (over 50% of patients), followed by nifedipine, felodipine, verapamil, and diltiazem. Differences in new nonvertebral fractures within 30 days of antibiotic prescription were not significant between the two groups. Because clarithromycin is an inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme, its co-use with CCBs may lead to harmful blood concentrations of CCBs that are metabolized by CYP3A4; however, in this study the risk of fracture was similar to that with azithromycin (which does not inhibit CYP3A4).
Calcium channel blocker (CCB) use in elderly patients lowers blood pressure and can increase the risk of falls and fractures. These drugs are metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme, and blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor of CYP3A4, whereas azithromycin is not.