No information provided.
Mitosol® is contraindicated in patients that have demonstrated a hypersensitivity to mitomycin in the past. 4.2 Pregnant women Mitosol® may cause fetal harm when administered to a pregnant woman. Mitomycin administered parenterally has been shown to be teratogenic in mice and rats when given at doses equivalent to the usual human intravenous dose. Mitosol® is contraindicated in women who are or may become pregnant during therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
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, conjunctivial necrosis, thin-walled bleb
Cornea: corneal endothelial damage, epithelial defect, anterior synechiae, superficial punctuate keratitis, Descemet's detachment, induced astigmatism
EndophthalmitisHypotony: 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.
Mitosol® is an antimetabolite indicated for use as an adjunct to ab externo glaucoma surgery.
The systemic exposure of mitomycin following ocular administration of Mitosol® in humans is unknown. Based on a comparison of the proposed dose of up to 0.2 mg to intravenous (IV) doses of mitomycin used clinically for treatment of oncologic indications (up to 20 mg/m2), systemic concentrations in humans upon ocular administration are expected to be multiple orders of magnitude lower than those achieved by IV administration.
MetabolismIn humans, mitomycin is cleared from ophthalmic tissue after intraoperative topical application and irrigation, as metabolism occurs in other affected tissues. Systemic clearance is affected primarily by metabolism in the liver. The rate of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways.
ExcretionApproximately 10% of an injectable dose of mitomycin is excreted unchanged in the urine. Since metabolic pathways are saturated at relatively low doses, the percent of a dose excreted in urine increases.
Teratogenic Effects: Pregnancy Category X (see CONTRAINDICATIONS).
Mitosol® is a sterile lyophilized mixture of mitomycin and mannitol, which, when reconstituted with Sterile Water for Injection, provides a solution for application in glaucoma filtration surgery. Mitosol® is supplied in vials containing 0.2 mg of mitomycin. Each vial also contains mannitol 0.4 mg, at a 1:2 ratio of mitomycin to mannitol. Each mL of reconstituted solution contains 0.2 mg mitomycin and has a pH between 5.0 and 8.0. 4.
Mitosol® (mitomycin for solution) is available in a kit containing:
One Vial containing 0.2 mg mitomycin
One 1 mL syringe (Sterile Water For Injection) with Connector
One Plunger Rod
One Vial Adapter with Spike
One 1 mL TB Syringe, Luer Lock
One Sponge Container
Six 3 mm Absorbent Sponges
Six 6 mm Absorbent Sponges
Six Half Moon Sponges
One Instrument Wedge Sponge
One Alcohol Prep Pad, Sterile
One Chemotherapy Waste Bag
Three kits are supplied in each carton (NDC 49771-002-03).
Storage and Handling StorageStore kits at 20° - 25° C (68° - 77° F). Protect from light.
Handling ProceduresProcedures for Proper Handling and Disposal of anti-cancer drugs should be followed. Appropriate containment and disposal devices are included within the Mitosol® (mitomycin for solution) Kit for Ophthalmic Use.
Manufactured for: Mobius Therapeutics, LLC 4041 Forest Park Avenue St. Louis, MO 63108. Revised 01/2012
Included as part of the PRECAUTIONS section.
PRECAUTIONS Cell DeathMitomycin 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.
HypotonyThe use of mitomycin has been associated with an increased instance of post-operative hypotony.
Cataract FormationUse in phakic patients has been correlated to a higher instance of lenticular change and cataract formation.
Patient Counseling InformationAdequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with Mitosol®. Intravenous administration of mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical injectable dose in humans, mitomycin produces a greater than 100 percent increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50 percent increase in tumor incidence in female Swiss mice.
The effect of Mitosol® on fertility is unknown.
Use In Specific Populations PregnancyTeratogenic Effects: Pregnancy Category X (see CONTRAINDICATIONS).
Nursing MothersIt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Mitosol®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. It is recommended that women receiving Mitosol® not breast feed because of the potential for serious adverse reactions in nursing infants.
Pediatric UseSafety and effectiveness in pediatric patients have not been established.
Geriatric UseNo overall differences in safety and effectiveness have been observed between elderly and younger patients.
Mitosol® is intended for topical application to the surgical site of glaucoma filtration surgery. It is not intended for intraocular administration. If intraocular administration occurs, cell death leading to corneal infarction, retinal infarction, and ciliary body atrophy may result.
Method of Reconstitution: Each vial of Mitosol® contains 0.2 mg of mitomycin and mannitol in a 1:2 concentration ratio. To reconstitute, add 1 mL of Sterile Water for Injection, then shake to dissolve. If product does not dissolve immediately, allow to stand at room temperature until the product dissolves into solution.
Method of Use: Sponges provided within the Mitosol® Kit should be fully saturated with the entire reconstituted contents in the manner prescribed in the Instructions for Use. A treatment area approximating 10mm x 6mm +/- 2mm should be treated with the Mitosol®. Apply fully saturated sponges equally to the treatment area, in a single layer, with the use of a surgical forceps. Keep the sponges on the treatment area for two (2) minutes, then remove and return to the Mitosol® Tray for defined disposal in the Chemotherapy Waste Bag provided.
StabilityLyophilized Mitosol® stored at controlled room temperature (i.e., 20 - 25°C or 68° - 77° F) is stable for the shelf life indicated on the package. Avoid excessive heat. Protect from light.
Reconstituted with Sterile Water for Injection at a concentration of 0.2 mg/ml, mitomycin is stable for one (1) hour at room temperature.
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, conjunctivial necrosis, thin-walled bleb
Cornea: corneal endothelial damage, epithelial defect, anterior synechiae, superficial punctuate keratitis, Descemet's detachment, induced astigmatism
EndophthalmitisHypotony: 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.
DRUG INTERACTIONSNo information provided.
