title: How frequently are contraindicated or warned against combinations of drugs prescribed to patients receiving long-term opioid therapy for chronic pain?
abstract: OBJECTIVE
  To analyse the proportion of patients treated with an opioid for chronic pain who were prescribed concomitant medications that are warned against or contraindicated in the German summary of product characteristics to determine if warnings on drug-drug interactions (DDIs) are observed.
  
  
  METHODS
  This retrospective analysis used longitudinal aggregated patient data from the Intercontinental Marketing Services Disease Analyzer in Germany. Patients with two or more prescriptions of morphine, hydromorphone, oxycodone or tramadol from 1 January 2006 to 31 December 2008 were included; drugs prescribed within 30 days of an opioid prescription were identified as concomitant medications. The frequency of concomitant treatment with drugs warned against or contraindicated in the German opioid summary of product characteristics was determined. Concomitant treatment with drugs metabolised by CYP3A4 inhibitors and inducers and CYP2D6 inhibitors was also considered.
  
  
  RESULTS
  The Intercontinental Marketing Services database contained 13,405 eligible patients; 72% had concomitant diseases which may increase the risk for DDIs (hypertension, diabetes mellitus, renal failure, renal glomerular disease or renal tubulointerstitial disease). Very few patients received concomitant prescriptions of an opioid with a contraindicated drug. Many patients were prescribed opioids concomitantly with drugs with potential for harmful safety-related DDIs or DDIs that alter the effectiveness of one or more of the opioids. A large proportion of all concomitant prescriptions with potential for DDIs were given to at-risk patients aged 65 years and older.
  
  
  CONCLUSIONS
  Many patients that received an opioid for chronic pain were prescribed concomitant medications with the potential for safety-related DDIs or interactions that would alter the effectiveness of the opioid.
authors.affiliation: Global Medical Affairs, GMAL Mature Products, Johnson & Johnson Pharmaceutical Services, LLC, Baar, Switzerland. urichar1@its.jnj.com
authors.forename: Ute
authors.initials: U
authors.lastname: Richarz
authors.forename: Adam
authors.initials: A
authors.lastname: Jacobs
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D059350:Chronic Pain / Q000188:drug therapy*; D000075202:Contraindications; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D016208:Databases, Factual; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D005858:Germany; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010818:Practice Patterns, Physicians' / Q000592:standards / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human