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Buitrago E, Lagomarsino E, Mato G, Schaiquevich P. Stability of Melphalan Solution for Intravitreal Injection for Retinoblastoma. JAMA Ophthalmol. 2014;132(11):1372–1373. doi:https://doi.org/10.1001/jamaophthalmol.2014.2324
Intravitreal injections for the treatment of retinoblastoma have been gaining relevance among ophthalmologists, supported by reports on outcome and improvement of the administration technique.1 Currently, doses up to 30 μg per injection are used according to an extensively described technique for intravitreal injection that minimizes the risk of extraocular dissemination of tumor cells.2
The commercial form of melphalan (Alkeran) contains 50 mg of melphalan to be reconstituted in 10 mL of vehicle,3 but each intravitreal injection consists of 30 μg of melphalan (its 1667th part). The rest of the vial is discarded. Specifically in countries with limited resources, this procedure may be optimized to prevent disposal of active agent and preserve it for future patients. The package insert states that after dilution (<0.45 mg/mL) of the reconstituted commercial formulation with sterile saline, the administration should be completed within 60 minutes of reconstitution because of the instability of melphalan.3 This degradation corresponds to a spontaneous hydrolysis to monohydroximelphalan and dihydroximelphalan.3,4 A solution of 400 μg/mL of melphalan in saline at 20°C lost 10% of its content in 4.5 hours; the same loss was attained after 2.4 hours at 25°C, a common room temperature in many clinical centers.4
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