title: Balancing risk in ophthalmic prescribing: assessing the safety of anti-VEGF therapies and the risks associated with unlicensed medicines.
abstract: Vascular endothelial growth factor (VEGF) inhibitor medications such as ranibizumab, pegaptanib and bevacizumab are in use for the treatment of neovascular age-related macular degeneration (AMD) and other retinal conditions, although only ranibizumab and pegaptanib are approved for these conditions. In contrast, bevacizumab was developed for the intravenous systemic treatment of colorectal cancer and is not formulated for intravitreal use, but is commonly used off-label in ophthalmology. European Union legislation permits the use of drugs outside the terms of their licence ('off-label') only under certain circumstances, such as during clinical trials, compassionate/named patient use in the absence of a licensed alternative, emergency scenarios (e.g., pandemics) or at the discretion of a treating physician. In such cases, patients should be fully informed regarding their treatment and any potential risks involved. Off-label drug use can be an important tool to provide patients with treatment in cases of unmet medical need. However, the use of an unlicensed medicinal product, when a suitable licensed alternative is available, puts prescribing physicians at risk of liability if safety issues arise. Emerging clinical evidence suggests safety differences exist between ranibizumab and bevacizumab.
authors.affiliation: Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk i32, Cleveland, OH 44195, USA. pkkaiser@aol.com
authors.forename: Peter K
authors.initials: PK
authors.lastname: Kaiser
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cruess
authors.forename: Peter
authors.initials: P
authors.lastname: Bogaert
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Khunti
authors.forename: Simon P
authors.initials: SP
authors.lastname: Kelly
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D017277:Drug Approval; D004335:Drug and Narcotic Control; D005062:European Union; D006801:Humans; D007880:Legislation, Drug; D056687:Off-Label Use; D055553:Prescription Drugs; D000069579:Ranibizumab; D018570:Risk Assessment; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D057135:Wet Macular Degeneration / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; D055553:Prescription Drugs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib; D000068258:Bevacizumab; D000069579:Ranibizumab