Product Elements:
Mitosol mitomycin mitosol mitomycin mitomycin mitomycin mannitol sterile water water water
Indications and Usage:
1 indications and usage mitosol ® is an antimetabolite indicated for use as an adjunct to ab externo glaucoma surgery. mitosol ® is an antimetabolite indicated as an adjunct to ab externo glaucoma surgery. ( 1 )
Warnings and Cautions:
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.
Read more... 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 )] .
Dosage and Administration:
2 dosage and administration mitosol ® is intended for topical application to the surgical site of glaucoma filtration surgery. it is not intended for intraocular administration. ( 2 ) ⢠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 has dissolved into solution. ( 2.2 ) ⢠fully saturate sponges provided within the mitosol ® kit utilizing the entire reconstituted contents of the vial in the manner prescribed in the instructions for use. ( 2.3 ) ⢠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. ( 2.3 ) 2.1 important administration instructions mitoso
Read more...l ® is intended for topical application to the surgical site of glaucoma filtration surgery. mitosol ® is a cytotoxic drug. 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. verify pregnancy status in females of reproductive potential prior to using mitosol ® . 2.2 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. 2.3 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. 2.4 stability lyophilized mitosol ® stored at 20°c to 25°c (68°f to 77°f) is stable for the shelf life indicated on the package. avoid excessive heat. protect from light. reconstituted with 1 ml of sterile water for injection at a concentration of 0.2 mg/ml, mitomycin is stable for one (1) hour at room temperature.
Dosage Forms and Strength:
3 dosage forms and strengths 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. each vial contains a sterile lyophilized mixture of 0.2 mg mitomycin and 0.4 mg mannitol; when reconstituted with sterile water for injection, the solution contains 0.2 mg/ml mitomycin. ( 3 )
Contraindications:
4 contraindications ⢠hypersensitivity to mitomycin. ( 4.1 ) 4.1 hypersensitivity mitosol ® is contraindicated in patients that have demonstrated a hypersensitivity to mitomycin in the past.
Adverse Reactions:
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 e
Read more...xtension 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.
Use in Specific Population:
8 use in specific populations 8.1 pregnancy risk summary based on findings in animals and mechanism of action [see clinical pharmacology ( 12.1 )] , mitosol ® can cause fetal harm when administered to a pregnant woman. there are no available data on mitosol ® use in pregnant women to inform the drug-associated risk. in animal reproduction studies, parenteral administration of mitomycin resulted in teratogenicity ( see data ). advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. data animal data parenteral administration of mitomycin in animal reproduction studies produced fetal malformations and embryofetal lethality. 8.2 lactation risk summary there are no data on the presence of mitomycin in
Read more...human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during and for 1 week following administration of mitosol ® . 8.3 females and males of reproductive potential mitosol ® can cause fetal harm when administered to pregnant women [see use in specific populations ( 8.1 )] . pregnancy testing verify pregnancy status in females of reproductive potential prior to using mitosol ® . 8.4 pediatric use safety and effectiveness in pediatric patients have not been established. 8.5 geriatric use no overall differences in safety and effectiveness have been observed between elderly and younger patients.
Use in Pregnancy:
8.1 pregnancy risk summary based on findings in animals and mechanism of action [see clinical pharmacology ( 12.1 )] , mitosol ® can cause fetal harm when administered to a pregnant woman. there are no available data on mitosol ® use in pregnant women to inform the drug-associated risk. in animal reproduction studies, parenteral administration of mitomycin resulted in teratogenicity ( see data ). advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. data animal data parenteral administration of mitomycin in animal reproduction studies produced fetal malformations and embryofetal lethality.
Pediatric Use:
8.4 pediatric use safety and effectiveness in pediatric patients have not been established.
Geriatric Use:
8.5 geriatric use no overall differences in safety and effectiveness have been observed between elderly and younger patients.
Description:
11 description mitomycin is an antibiotic isolated from the broth of streptomyces verticillus yingtanensis which has been shown to have antimetabolic activity. mitomycin is a blue-violet crystalline powder with the molecular formula of c 15 h 18 n 4 o 5 and a molecular weight of 334.33. its chemical name is 7-amino-9α-methoxymitosane and it has the following structural formula: 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. structural formula
Clinical Pharmacology:
12 clinical pharmacology 12.1 mechanism of action mitosol ® inhibits the synthesis of deoxyribonucleic acid (dna). the guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. cellular rna and protein synthesis may also be suppressed. 12.3 pharmacokinetics absorption 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/m 2 ), systemic concentrations in humans upon ocular administration are expected to be multiple orders of magnitude lower than those achieved by iv administration. elimination metabolism in 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 rat
Read more...e of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways. excretion approximately 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.
Mechanism of Action:
12.1 mechanism of action mitosol ® inhibits the synthesis of deoxyribonucleic acid (dna). the guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. cellular rna and protein synthesis may also be suppressed.
Pharmacokinetics:
12.3 pharmacokinetics absorption 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/m 2 ), systemic concentrations in humans upon ocular administration are expected to be multiple orders of magnitude lower than those achieved by iv administration. elimination metabolism in 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. excretion approximately 10% of an injectable dose of mitomycin is excreted unchanged in the urine. since metabolic pathways are saturated at relat
Read more...ively low doses, the percent of a dose excreted in urine increases.
Nonclinical Toxicology:
13 nonclinical toxicology 13.1 carcinogenesis, mutagenesis, impairment of fertility adequate 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.
Carcinogenesis and Mutagenesis and Impairment of Fertility:
13.1 carcinogenesis, mutagenesis, impairment of fertility adequate 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.
Clinical Studies:
14 clinical studies in placebo-controlled studies reported in the medical literature, mitomycin reduced intraocular pressure (iop) by 3 mmhg in patients with open-angle glaucoma when used as an adjunct to ab externo glaucoma surgery by month 12. in studies with a historical control reported in the medical literature, mitomycin reduced intraocular pressure (iop) by 5 mmhg in patients with open-angle glaucoma when used as an adjunct to ab externo glaucoma surgery by month 12.
How Supplied:
16 how supplied/storage and handling 16.1 how supplied 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 safety 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 protective foam pouch one chemotherapy waste bag one label, mmc (mitomycin) three kits are supplied in each carton (ndc 49771-002-03). 16.2 storage and handling storage store kits at 20°c to 25°c (68°f to 77°f). avoid excessive heat. protect from light. handling procedures mitosol ® is a cytotoxic drug. procedures 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.
Information for Patients:
17 patient counseling information ⢠instruct patients to discuss with their physician if they are pregnant or if they might become pregnant [see use in specific populations ( 8.1 )]. ⢠instruct patients to discuss with their physician if they have demonstrated a hypersensitivity to mitomycin in the past [see contraindications ( 4.1 )]. ⢠nursing mothers should be advised that it is not known if mitosol ® is excreted in human milk. because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during and for 1 week following administration of mitosol ® [see use in specific populations ( 8.2 )]. ⢠patients should be advised of the toxicity of mitosol ® and potential complications. manufactured for: mobius therapeutics, llc 1000 executive parkway suite 224 st. louis, mo 63141
Package Label Principal Display Panel:
Principal display panel - vial label vial label ndc 49771-002-02 mitosol ® (mitomycin for solution) 0.2 mg/vial lyophilized mitomycin for reconstitution protect from light. single use vial dose: see package insert. rx only store at 20°-25°c (68°-77°f). manufactured for: mobius therapeutics, llc 1000 executive parkway suite 224 st. louis, mo 63141 manufactured by: intas pharmaceuticals ltd. ahmedabad-382 210, india. mfg. lic. no.: g/1026 10 9750 2 658376 inl5021 principal display panel - vial label
Principal display panel - outer kit package outer kit package mitosol ® (mitomycin for solution) 0.2 mg/vial kit for ophthalmic use manufactured for: mobius therapeutics, llc 1000 executive parkway suite 224 st. louis, mo 63141 usa +1 314-615-6930 1-877-eye-mito (1-877-393-6486) rx only us patents #7,806,265, #8,186,511, #d685,962, #d685,963, #9,205,075, #9,539,241 and #9,649,428; other international patents issued and pending. ©2019 mobius therapeutics, llc mobius therapeutics⢠a1426418-1 rev. 8/19 ndc #49771-002-01 re-order #mob.2 each mitosol ® kit contains: one chemotherapy waste bag one instructions for use one package insert one inner tray two patient chart labels inner tray contains: one vial containing 0.2 mg mitomycin (inside protective foam pouch) one 1 ml syringe (sterile water for injection) with safety connector one plunger rod one vial adaptor with spike (inside protective foam pouch) one 1 ml tb syringe, luer lock one sponge container containing: six 3 mm absorbent sponges six 6 mm absorbent sponges six half moon sponges one instrument wedge sponge one label, mmc contents sterile in unopened undamaged package. storage: store kits at 20° - 25° c (68° - 77° f). protect from light. hd caution: hazardous drug observe special handling, administration and disposal requirements principal display panel - outer kit package