title: Post-marketing surveillance of ischaemic optic neuropathy in male veterans co-prescribed phosphodiesterase-5 inhibitors with organic nitrates or alpha-blockers.
abstract: BACKGROUND
  The cause of nonarteritic anterior ischaemic optic neuropathy (ION) is unknown, although assumed to be related to transient vascular insufficiency of the optic nerve head. Because the interaction of phosphodiesterase-5 (PDE-5) inhibitors with either an organic nitrate or alpha-blocker may theoretically increase the risk of ION, we conducted a screening study to determine if such a risk might exist.
  
  
  METHODS
  Retrospective cohort study of male veterans with ION and possible ION. The national Veterans Health Administration (VHA) clinical database was cross-referenced (linked) with the VHA pharmacy database looking for specific drug combinations.
  
  
  RESULTS
  Compared with no use, the relative risk (RR) of ION and possible ION for men prescribed both PDE-5 inhibitor and organic nitrate was 1.41 (95% CI 0.85, 2.33). Similarly, the RR of ION and possible ION with concurrent prescription of PDE-5 inhibitor and alpha-blocker was 1.21 (95% CI 1.01, 1.44). When risk was measured against use of a PDE-5 inhibitor alone, the RR was 1.29 (95% CI 0.78, 2.16) for PDE-5 inhibitor and organic nitrate and 1.12 (95% CI 0.92, 1.35) for PDE-5 inhibitor and alpha-blocker.
  
  
  CONCLUSIONS
  We linked two large national databases to screen for a potentially important drug-drug-disease interaction. There was no increase in risk of ION and possible ION in men dispensed a PDE-5 inhibitor with either organic nitrates or an alpha-blocker compared with men dispensed PDE-5 inhibitor alone. An incidental observation that a substantial number of men were prescribed both an organic nitrate and a PDE-5 inhibitor within a single dispensing period raises concerns over non-ocular safety issues. The wisdom of co-dispensing medications that are contraindicated may deserve a broader audience.
authors.affiliation: VISN-8 Patient Safety Center of Inquiry, James A. Haley VA Hospital, Tampa, Florida, USA. Dustin.French@va.gov
authors.forename: Dustin D
authors.initials: DD
authors.lastname: French
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Margo
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects*; D000368:Aged; D015331:Cohort Studies; D016208:Databases, Factual; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000009:adverse effects*; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced*; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D012306:Risk; D014481:United States; D014493:United States Department of Veterans Affairs; D014728:Veterans
chemical_list: D000317:Adrenergic alpha-Antagonists; D009566:Nitrates; D010726:Phosphodiesterase Inhibitors