Abstract
PurposeTo investigate the extent to which clinicians avoid well-established drug-drug interactions that cause statin-induced myopathy. We hypothesised that clinicians would avoid combining erythromycin or verapamil/diltiazem respectively with atorvastatin or simvastatin. In patients with statin-fibrate combination therapy, we hypothesised that gemfibrozil was avoided to the preference of bezafibrate or fenofibrate. When combined with verapamil/diltiazem or fibrates, we hypothesized that the dispensed doses of atorvastatin/simvastatin would be decreased.MethodsCross-sectional analysis of nationwide dispensing data. Odds ratios of interacting erythromycin, verapamil/diltiazem versus respective prevalence of comparator drugs doxycycline, amlodipine/felodipine in patients co-dispensed interacting statins simvastatin/atorvastatin versus patients unexposed (pravastatin/fluvastatin/rosuvastatin) was calculated. For fibrates, OR of gemfibrozil versus fenofibrate/bezafibrate in patients co-dispensed any statin was assessed.ResultsOR of interacting erythromycin versus comparator doxycycline did not differ between patients on interacting and comparator statins either in patients dispensed high or low statin doses (adjusted OR 0.87; 95% CI 0.60–1.25 and 0.92; 95% CI 0.69–1.23). Interacting statins were less common among patients dispensed verapamil/diltiazem as compared to patients on amlodipine/felodipine (OR high dose 0.62; CI 0.56–0.68 and low dose 0.63; CI 0.58–0.68). Patients on any statin were to a lesser extent dispensed gemfibrozil compared to patients not dispensed a statin (OR high dose 0.65; CI 0.55–0.76 and low dose 0.70; CI 0.63–0.78). Mean DDD (SD) for any statin was substantially higher in patients co-dispensed gemfibrozil 178 (149) compared to patients on statin monotherapy 127 (93), (p<0.001).ConclusionsPrescribers may to some extent avoid co-prescription of statins with calcium blockers and fibrates with an increased risk of myopathy. We found no evidence for avoiding co-prescriptions of statins and antibiotics with an increased risk of statin-induced adverse drug reactions. Co-prescription of statins and gemfibrozil is paradoxically associated with a marked increased statin dose, further aggravating the risk for severe myopathy.
Highlights
The introduction of HMG-CoA reductase inhibitors, has had a major impact on the modern management of cardiovascular disease
odds ratios (OR) of interacting erythromycin versus comparator doxycycline did not differ between patients on interacting and comparator statins either in patients dispensed high or low statin doses
Interacting statins were less common among patients dispensed verapamil/diltiazem as compared to patients on amlodipine/felodipine (OR high dose 0.62; confidence intervals (CI) 0.56–0.68 and low dose 0.63; CI 0.58–0.68)
Summary
The introduction of HMG-CoA reductase inhibitors, (statins) has had a major impact on the modern management of cardiovascular disease. The remaining statins, are either eliminated unchanged (pravastatin and rosuvastatin) or are subject for a clearance based on other metabolic pathways (fluvastatin), and may be an alternative for patients in need of long-term treatment with these drugs [2,11,14,19,20,21] Another strategy may be to use drugs with a similar indication that do not significantly inhibit CYP3A4 such as doxycycline instead of erythromycin and any of the alternative calcium antagonists amlodipine or felodipine instead of diltiazem or verapamil, or to decrease the administered statin dose [22,23,24]. In Sweden, SFINX (Swedish Finnish interaction X referencing) alerts approximately 80% of Swedish doctors for drug-drug interactions at the moment of prescribing [35,36,37]
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