Michael W Stewart1, Raja Narayanan2, Vishali Gupta3, Philip J Rosenfeld4, Daniel F Martin5, Usha Chakravarthy6. 1. Department of Ophthalmology, Mayo School of Medicine, Jacksonville, Florida. Electronic address: stewart.michael@mayo.edu. 2. LV Prasad Eye Institute, Hyderabad, India. 3. Institute of Medical Education and Research, Chandigarh, India. 4. Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida. 5. Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. 6. Department of Ophthalmology, Queen's University of Belfast, Belfast, Northern Ireland.
Abstract
PURPOSE: To report the recent controversy surrounding the intraocular use of bevacizumab in India and its relationship to the broader problems of off-label drug use, medication compounding, and drug counterfeiting. DESIGN: Perspective. METHODS: Data for this perspective were obtained from several sources. Literature reviews for compounding-related endophthalmitis and drug counterfeiting were performed. Supplemental information was obtained through targeted Google searches for related published manuscripts. First-hand accounts of negotiations between representatives of the Vitreoretinal Society of India (VRSI) and India's Central Drugs Standards Control Organization (CDSCO) were provided by 2 of the authors (R.N., V.G.). RESULTS: In December, 2015, 15 cases of intraocular inflammation following injections of counterfeit bevacizumab occurred in Gujarat, India. CDSCO reacted by prohibiting the use of intraocular bevacizumab throughout the country. Intense negotiations between the VRSI and CDSCO resulted in the permission to use bevacizumab in accordance with new safety guidelines. These include an enhanced informed consent process, the stamping of the Kezzler code on all bevacizumab vials, a real-time digital verification process between the end user and Roche Pharmaceuticals, and mandatory destruction of empty drug vials. CONCLUSION: Counterfeit bevacizumab has caused outbreaks of sterile and infectious postinjection endophthalmitis in at least 3 countries during the past 5 years and has entered the supply chain in other countries. Physicians and compounding pharmacists need to be aware that international counterfeiters have targeted bevacizumab.
PURPOSE: To report the recent controversy surrounding the intraocular use of bevacizumab in India and its relationship to the broader problems of off-label drug use, medication compounding, and drug counterfeiting. DESIGN: Perspective. METHODS: Data for this perspective were obtained from several sources. Literature reviews for compounding-related endophthalmitis and drug counterfeiting were performed. Supplemental information was obtained through targeted Google searches for related published manuscripts. First-hand accounts of negotiations between representatives of the Vitreoretinal Society of India (VRSI) and India's Central Drugs Standards Control Organization (CDSCO) were provided by 2 of the authors (R.N., V.G.). RESULTS: In December, 2015, 15 cases of intraocular inflammation following injections of counterfeit bevacizumab occurred in Gujarat, India. CDSCO reacted by prohibiting the use of intraocular bevacizumab throughout the country. Intense negotiations between the VRSI and CDSCO resulted in the permission to use bevacizumab in accordance with new safety guidelines. These include an enhanced informed consent process, the stamping of the Kezzler code on all bevacizumab vials, a real-time digital verification process between the end user and Roche Pharmaceuticals, and mandatory destruction of empty drug vials. CONCLUSION: Counterfeit bevacizumab has caused outbreaks of sterile and infectious postinjection endophthalmitis in at least 3 countries during the past 5 years and has entered the supply chain in other countries. Physicians and compounding pharmacists need to be aware that international counterfeiters have targeted bevacizumab.