Post-marketing surveillance of ischaemic optic neuropathy in male veterans co-prescribed phosphodiesterase-5 inhibitors with organic nitrates or alpha-blockers

Drug Saf. 2008;31(3):241-7. doi: 10.2165/00002018-200831030-00005.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic alpha-Antagonists / adverse effects*
  • Aged
  • Cohort Studies
  • Databases, Factual
  • Drug Interactions
  • Humans
  • Male
  • Middle Aged
  • Nitrates / adverse effects*
  • Optic Neuropathy, Ischemic / chemically induced*
  • Phosphodiesterase Inhibitors / adverse effects*
  • Product Surveillance, Postmarketing
  • Retrospective Studies
  • Risk
  • United States
  • United States Department of Veterans Affairs
  • Veterans

Substances

  • Adrenergic alpha-Antagonists
  • Nitrates
  • Phosphodiesterase Inhibitors