title: Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy.
abstract: BACKGROUND
  Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia.
  
  
  METHODS
  Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program.
  
  
  RESULTS
  We included 2742 ambulatory statin-treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/- SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients.
  
  
  CONCLUSIONS
  CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.
authors.affiliation: Division of Clinical Pharmacology & Toxicology, University Hospital, Basel, Switzerland.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Rätz Bravo
authors.forename: Lydia
authors.initials: L
authors.lastname: Tchambaz
authors.forename: Anita
authors.initials: A
authors.lastname: Krähenbühl-Melcher
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Hess
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Schlienger
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
mesh_terms: D000368:Aged; D000553:Ambulatory Care; D001189:Aryl Hydrocarbon Hydroxylases / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000069059:Atorvastatin; D015897:Comorbidity; D003430:Cross-Sectional Studies; D016572:Cyclosporine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D004077:Digoxin / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D007211:Indoles / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D009525:Niacin / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D010089:Oxidoreductases, N-Demethylating / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D010820:Physicians / Q000145:classification / Q000706:statistics & numerical data; D017035:Pravastatin / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D015995:Prevalence; D011358:Product Surveillance, Postmarketing / Q000379:methods; D011758:Pyrroles / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D019821:Simvastatin / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011758:Pyrroles; D009525:Niacin; D000077340:Fluvastatin; D004077:Digoxin; D016572:Cyclosporine; D000069059:Atorvastatin; D019821:Simvastatin; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D017035:Pravastatin
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