title: Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population.
abstract: OBJECTIVE
  The co-administration of cytochrome P450 3A4 (CYP3A4) inhibitors with simvastatin or atorvastatin (CYP3A4-metabolised statins) is associated with increased statin exposure and can increase the risk of adverse drug reactions. The aim of this study was to measure the concomitant exposure of patients to CYP3A4-metabolised statins and CYP3A4 inhibitors in the UK primary care population.
  
  
  METHODS
  The co-administration of statins and CYP3A4 inhibitors during 2008 was examined in the General Practice Research Database, a large nationally representative UK primary care database. All known inhibitors were included with labelled inhibitors identified using the Medicines and Healthcare products Regulatory Agency Drug Safety Update and UK summary of product characteristics for statins. Exposure was examined in patients overall, patients 65 years and older and those prescribed higher doses of statins.
  
  
  RESULTS
  There were 364,574 patients included in the analyses. Ninety-three percent of the patients were prescribed CYP3A4-metabolised statins, most whom received simvastatin (72%) and atorvastatin (24%). Approximately one third (30%) of the patients prescribed a CYP3A4-metabolised statin had also been prescribed a concomitant CYP3A4 inhibitor during the study period, including 11% prescribed a concomitant labelled inhibitor, with an annualised median days of concomitant use of 173 days, predominantly involving macrolide antibiotics and calcium channel blockers co-prescriptions. Rates were higher in the subgroup aged 65 and over and in those on high dose statins.
  
  
  CONCLUSIONS
  The co-prescription of CYP3A4-metabolised statins and CYP3A4 inhibitors is common in UK primary care. This co-prescription suggests the limited appreciation of potential interactions and Medicines and Healthcare products Regulatory Agency safety advice, with the potential to increase likelihood for side effects amongst patients. Strategies to reduce drug interactions with potential adverse effects should be targeted at prescribers and pharmacists.
authors.affiliation: Barnet General Hospital, Wellhouse Lane, Barnet, London, UK. abakhai@bcf.nhs.uk
authors.forename: Ameet
authors.initials: A
authors.lastname: Bakhai
authors.forename: Una
authors.initials: U
authors.lastname: Rigney
authors.forename: Samuel
authors.initials: S
authors.lastname: Hollis
authors.forename: Cathy
authors.initials: C
authors.lastname: Emmas
mesh_terms: D000367:Age Factors; D000368:Aged; D000069059:Atorvastatin; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D016208:Databases, Factual; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data; D011320:Primary Health Care / Q000706:statistics & numerical data; D011758:Pyrroles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D019821:Simvastatin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006113:United Kingdom
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human