Mitosol

5 WARNINGS AND PRECAUTIONS • Cell Death : Mitomycin is cytotoxic. Use of mitomycin in concentrations higher than 0.2 mg/mL or use for longer than 2 minutes may lead to unintended corneal and/or scleral damage including thinning or perforation. Direct contact with the corneal endothelium will result in cell death. ( 5.1 ) • Hypotony : The use of mitomycin has been associated with an increased incidence of post-operative hypotony. ( 5.2 ) • Cataract Development : Use in phakic patients has been correlated to a higher incidence of lenticular change and cataract formation. ( 5.3 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise of potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to use. ( 5.4 , 8.1 , 8.3 ) 5.1 Cell Death Mitomycin is cytotoxic. Use of mitomycin in concentrations higher than 0.2 mg/mL or use for longer than 2 minutes may lead to unintended corneal and/or scleral damage including thinning or perforation. Direct contact with the corneal endothelium will result in cell death. 5.2 Hypotony The use of mitomycin has been associated with an increased incidence of post-operative hypotony. 5.3 Cataract Formation Use in phakic patients has been correlated to a higher incidence of lenticular change and cataract formation. 5.4 Embryo-Fetal Toxicity Based on findings in animals and mechanism of action, Mitosol ® can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, parenteral administration of mitomycin resulted in teratogenicity [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.1 )] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Cell Death [see Warnings and Precautions ( 5.1 )] • Hypotony [see Warnings and Precautions ( 5.2 )] • Cataract Formation [see Warnings and Precautions ( 5.3 )] The most frequent adverse reactions to Mitosol ® occur locally and include hypotony, hypotony maculopathy, blebitis, endophthalmitis, vascular reactions, corneal reactions, and cataract. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mobius Therapeutics LLC at 1-877-393-6486 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Ophthalmic Adverse Reactions Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most frequent adverse reactions to Mitosol ® occur locally, as an extension of the pharmacological activity of the drug. These reactions include: Blebitis: bleb ulceration, chronic bleb leak, encapsulated/cystic bleb, bleb-related infection, wound dehiscence, conjunctival necrosis, thin-walled bleb Cornea: corneal endothelial damage, epithelial defect, anterior synechiae, superficial punctuate keratitis, Descemet's detachment, induced astigmatism Endophthalmitis Hypotony: choroidal reactions (choroidal detachment, choroidal effusion, serous choroidal detachment, suprachoroidal hemorrhage, hypotony maculopathy, presence of supraciliochoroidal fluid, hypoechogenic suprachoroidal effusion) Inflammation: iritis, fibrin reaction Lens: cataract development, cataract progression, capsule opacification, capsular constriction and/or capsulotomy rupture, posterior synechiae Retina: retinal pigment epithelial tear, retinal detachment (serous and rhegatogenous) Scleritis: wound dehiscence Vascular: hyphema, central retinal vein occlusion, hemiretinal vein occlusion, retinal hemorrhage, vitreal hemorrhage and blood clot, subconjunctival hemorrhage, disk hemorrhage Additional Reactions: macular edema, sclera thinning or ulceration, intraocular lens capture, disk swelling, malignant glaucoma, lacrimal drainage system obstruction, ciliary block, corneal vascularization, visual acuity decrease, cystic conjunctival degeneration, upper eyelid retraction, dislocated implants, severe loss of vision.