CENTER FOR DRUG EVALUATION AND RESEARCH

APPLICATION NUMBER:

022572Orig1s000

LABELING

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Mitosol® (mitomycin for solution) safely and effectively. See full prescribing information for Mitosol® (mitomycin for solution).Mitosol® (mitomycin for solution) Initial U.S. Approval: 1974

----------------------------INDICATIONS AND USAGE---------------------------Mitosol® is an antimetabolite indicated as an adjunct to ab externo glaucoma surgery. (1)

-----------------------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)

® contains 0.2 mg of mitomycin and mannitol in a 1:2 concentration ratio. To reconstitute, add 1 mL of Sterile Water for

immediately, allow to stand at room temperature until the product has

® Kit utilizing the

Instructions for Use. (2.2)

layer, with the use of a surgical forceps. Keep the sponges on the

Mitosol® Tray for defined disposal. (2.2)

---------------------DOSAGE FORMS AND STRENGTHS----------------------

0.4 mg mannitol; when reconstituted with Sterile Water for Injection, the solution contains 0.2 mg/mL mitomycin. (3)

-------------------------------CONTRAINDICATIONS------------------------------

-----------------------WARNINGS AND PRECAUTIONS------------------------

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

cell death. (5.1)

a higher instance of lenticular change and cataract formation. (5.3)

------------------------------ADVERSE REACTIONS-------------------------------® occur locally and

include hypotony, hypotony maculopathy, blebitis, endophthalmitis,

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.

See 17 for PATIENT COUNSELING INFORMATION Revised 01/2012

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION 2.1 Method of Reconstitution 2.2 Method of Use 2.3 Stability3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS

4.2 Pregnant women5 WARNINGS AND PRECAUTIONS

6 ADVERSE REACTIONS

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use11 DESCRIPTION12 CLINICAL PHARMACOLOGY

12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY

14 CLINICAL STUDIES16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are not listed.

Reference ID: 3083781

INDICATIONS AND USAGEMitosol® is an antimetabolite indicated for use as an adjunct to ab externo glaucoma surgery.

DOSAGE AND ADMINISTRATIONMitosol® 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: ® contains 0.2 mg of mitomycin and mannitol in a 1:2 concentration

Method of Use: ® Kit should be fully saturated with the entire reconstituted

2mm should be treated with the Mitosol®

and return to the Mitosol®

StabilityLyophilized Mitosol®

Reconstituted with 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 STRENGTHSMitosol® is a sterile lyophilized mixture of mitomycin and mannitol, which, when reconstituted with Sterile Water for

®

CONTRAINDICATIONS

HypersensitivityMitosol®

Pregnant womenMitosol® may cause fetal harm when administered to a pregnant woman. Mitomycin administered parenterally has

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.

WARNINGS AND PRECAUTIONS

Cell DeathMitomycin is cytotoxic. Use of mitomycin in concentrations higher than 0.2 mg/mL or use for longer than 2 minutes

corneal endothelium will result in cell death.

Hypotony

Cataract FormationUse in phakic patients has been correlated to a higher instance of lenticular change and cataract formation.

1.

2.

2.1

2.2

2.3

3.

4.

4.1

4.2

5.

5.1

5.2

5.3

FULL PRESCRIBING INFORMATION

Reference ID: 3083781

ADVERSE REACTIONS

Ophthalmic Adverse Reactions®

drug. These reactions include:

Blebitis: bleb ulceration, chronic bleb leak, encapsulated/cystic bleb, bleb-related infection, wound dehiscence,

Cornea: corneal endothelial damage, epithelial defect, anterior synechiae, superficial punctuate keratitis,

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:rupture, posterior synechiae

Retina: retinal pigment epithelial tear, retinal detachment (serous and rhegatogenous)

Scleritis: wound dehiscence

Vascular:

Additional Reactions: macular edema, sclera thinning or ulceration, intraocular lens capture, disk swelling,

USE IN SPECIFIC POPULATIONS

Pregnancysee Contraindications, 4.2).

Nursing Mothers

®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the

® not breast feed because of the potential for serious

Pediatric Use

Geriatric Use

DESCRIPTIONMitomycin is an antibiotic isolated from the broth of Streptomyces verticillus Yingtanensis which has been shown to

15 18N4 5 and a molecular weight of

6.

6.1

8.

8.1

8.3

8.4

8.5

11.

Reference ID: 3083781

Mitosol® is a sterile lyophiliized mixture of mitomycin and mannitol, which, when reconstituted with Sterile Water for ®

CLINICAL PHARMACOLOGY

Mechanism of ActionMitosol®

PharmacokineticsAbsorptionThe systemic exposure of mitomycin following ocular administration of Mitosol®

treatment of oncologic indications (up to 20 mg/m2), systemic concentrations in humans upon ocular administration

Metabolism

Excretion

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility®.

approximating the recommended clinical injectable dose in humans, mitomycin produces a greater than 100

incidence in female Swiss mice.The effect of Mitosol® on fertility is unknown.

CLINICAL STUDIES

12.

12.1

12.3

13.

13.1

14.

Reference ID: 3083781

Month 12.

HOW SUPPLIED/STORAGE AND HANDLING

How SuppliedMitosol®

Storage and Handling

Storage

Handling Procedures

®

PATIENT COUNSELING INFORMATION

see Contraindications, 4.2).

past (see Contraindications, 4.1).

®

decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the ® not breast feed because

see Use in Specific Populations, 8.3).

® and potential complications.

Manufactured for:

16.

16.1

16.2

17.

Reference ID: 3083781

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Checked by Approved by

Department Design Studio Marketing Packing Dev. Q.A. Q.A.

Signature

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Reference ID: 3083781

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