CONCOMITANT USE OF STATINS AND CYTOCHROME P 450 INHIBITORS IN CROATIA
Summary. It is known that coadministration of a statin and certain drugs that inhibit cytochrome P-450 may inhibit catabolism of statin, resulting in an increased concentration of statin in the blood and consequently, increased risk of certain side effects, e.g. myopathy. The aim of this study was to establish, for the first time, how many patients in Croatia concomitantly take statins with other drugs, and which drugs. Also, the aim was to determine how often statins are administered concomitantly with cytochrome P-450 inhibitors, and how many patients taking statin are therefore at increased risk of interactions and/or side effects. The data were collected from general practitioners’ health records all over Croatia during July and August 2004. The data for patients who were prescribed any statin between June 1, 2003 and June 1, 2004 were analysed. The records of 882 patients were analysed, 446 (50.6%) women, 422 (47.8%) men and 14 (1.6% ) of unidentified sex. The average age of women on statin was 65 years and of men 60 years. Of 882 patients, 772 patients (82%) were taking at least one more drug concurrently with statin. Of that number, 24% of patients concomitantly were taking one more drug, 20% two more drugs, 16 % three more drugs, 10% four more drugs, 8% five more drugs and 3% six more drugs. The average number of other drugs prescribed together with statin was 2.1±1.59 in men and 2.2±1.71 in women. The average age of patients who were taking another drug together with a statin did not significantly differ from that of patients receiving only statin. There were regional differences in the number of drugs prescribed together with a statin. In Osijek, the average number of drugs prescribed with a statin was 2.4±1.80, in Zagreb 2.2±1.64, in Rijeka 2.0±1.60, and in Split 1.8±1.44. The number of drugs prescribed with a statin in rural areas was 2.0±1.58, in urban areas 2.1±1.63 and in semi-urban areas 2.8±1.85. The therapeutic groups of drugs that are most frequently prescribed with a statin in Croatia are ACE inhibitors and their fixed combinations (32%), beta-receptor blockers and their fixed combinations (23%), selective calcium channel blockers (18%), anxiolytics (18%), vasodilators and organic nitrates (16%), antirheumatic drugs (11%), oral antidiabetics (11%), vitamin K antagonists, analgesics-antipyretics, diuretics (10%), antibiotics (8%), and angiotensin II antagonists and their fixed combinations (5%). All other drugs accounted for less than 5 %. Four percent of the patients take cytochrome P-450 inhibitors concomitantly with a statin. The most frequently used drug is verapamil, combination of verapamil and trandolapril, clarithromycin and diltiazem. Consequently, 3% of men and 5% of women are at increased risk of side effects. This sex difference is, however, not statistically significant. Patients between 70 and 74 years of age taking statins are in Croatia at the highest risk of interactions because 8% of them take concomitantly cytochrome P 450 inhibitors.