Effect of Regulatory Requirement for Patient-Specific Prescriptions for Off-Label Medications on the Use of Intravitreal Bevacizumab

Abstract

IMPORTANCE Requirements regulating pharmaceutical prescriptions can affect physicians' choice of therapy in a clinical setting. OBJECTIVE To evaluate the change in bevacizumab use after the regulatory requirement for patient-specific prescriptions (PSPs) for off-label medications in Ohio. DESIGN, SETTING, AND PARTICIPANTS This study retrospectively reviewed the aggregate data from the billing records of patients receiving 1.25-mg injections of bevacizumab, 0.3-or 0.5-mg injections of ranibizumab, or 2.0-mg injections of aflibercept for age-related macular degeneration or diabetic macular edema in a 9-member retinal specialty private practice. The review assessed 4488 intravitreal injections in the 3-month period before (May 1 to July 30, 2012) and 5253 injections in the 3-month period after (May 1 to July 30, 2013) the Ohio Board of Pharmacy's requirement of PSPs for bevacizumab. Relative proportions of the drugs used for intravitreal injections were calculated and frequencies were compared. A Likert scale survey was conducted among the 9 physicians to identify reasons for their change in prescription of bevacizumab. The survey inquired about (1) the burden of PSPs, (2) concern about differences in efficacy, and (3) concern about differences in safety. MAIN OUTCOMES AND MEASURES Difference in drug use before and after the PSP requirement for bevacizumab and the physicians' reasons for change in their drug use. RESULTS Bevacizumab use decreased from 2752 of 4488 pre-PSP injections (61.3%) to 1503 of 5253 post-PSP injections (28.6%), a change of −32.7% (95% CI, −34.6% to −30.8%; P < .001). Use of 0.5-mg ranibizumab injections increased from 1122 of 4488 pre-PSP injections (25.0%) to 1838 of 5253 post-PSP injections (35.0%), a change of 10.0% (95% CI, 8.2% to 11.8%; P < .001). Use of 0.3-mg ranibizumab injections increased from 0 of 4488 (before US Food and Drug Administration approval) to 429 of 5253 post-PSP injections (8.2%), a change of 8.2% (95% CI, 7.4% to 8.9%; P < .001). Use of aflibercept injections increased from 614 of 4488 pre-PSP injections (13.7%) to 1483 of 5253 post-PSP injections (28.2%), a change of 14.6% (95% CI, 13.0%-16.1%; P < .001). In the survey of the 9 physicians concerning their reasons for decreased use of bevacizumab, 7 (78%) strongly agreed and 1 (11%) agreed that the burden of PSPs changed their choice of drug used for injection. CONCLUSIONS AND RELEVANCE Use of bevacizumab was reduced by 32.7% 1 year after the regulatory requirement for PSPs for compounded (repackaged) medications. This change seemed to have more association with the requirement for PSPs than with a known change in efficacy or safety concerns. Although this study was based on a single US practice, regulation of repackaged medication for safety concerns should also consider the evaluation of treatment burden, cost, and adherence.

The association between myocardial infarction and intravitreal bevacizumab injection

“…Bevacizumab is an anti-VEGF agent that has been approved by the Food and Drug Administration (FDA) to treat colorectal cancer and glioblastoma, [ 7 , 8 ] but not as an intravitreal injection. [ 9 ] Ranibizumab was approved by the FDA in 2006 for the treatment of AMD, in 2010 for the treatment of RVO, and in 2012 for the treatment of DME. [ 9 , 10 ] Aflibercept was approved by the FDA in 2011 for the treatment of AMD, and 2014 for the treatment of DME.…”

“…[ 9 ] Ranibizumab was approved by the FDA in 2006 for the treatment of AMD, in 2010 for the treatment of RVO, and in 2012 for the treatment of DME. [ 9 , 10 ] Aflibercept was approved by the FDA in 2011 for the treatment of AMD, and 2014 for the treatment of DME. [ 9 , 11 ]…”

“…[ 9 , 10 ] Aflibercept was approved by the FDA in 2011 for the treatment of AMD, and 2014 for the treatment of DME. [ 9 , 11 ]…”

“…Despite use being off label, intravitreal bevacizumab (IVB) is often used because of its cost-effectiveness, and is also inevitably used without FDA approval because of its effectiveness for PDR vitreous hemorrhage with or without vitrectomy, neovascular glaucoma, and ROP. [ 6 , 9 , 12 – 14 ] However, IVB injection has side effects, such as worsening of the epiretinal membrane, subretinal fibrosis or tractional retinal detachment, and an increased risk of thromboembolism. [ 15 – 20 ] There has also been controversy regarding the possible association between bevacizumab and thromboembolic events.…”

Intravitreal Bevacizumab: Safety of multiple doses preparation from single vial in minor theater in tertiary care center

“…In our clinical practice, we usually use bevacizumab, an off-label drug initially prescribed for colon cancer treatment, whose ophthalmological efficacy has been well-demonstrated 8,9 . The low cost of I bevacizumab compared with other anti-VEGF agents is a deciding factor in its favor, particularly in the developing world.…”