Mitomycin (topical)

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# Overview
Mitomycin (topical) is a Antibiotic that is FDA approved for the treatment of ab externo glaucoma surgery.   Common adverse reactions include loss of appetite, nausea and vomiting and fever.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Mitomycin is an antimetabolite indicated for use as an adjunct to ab externo glaucoma surgery.

### Dosage
- mitomycin 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 mitomycin 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 mitomycin 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 mitomycin. 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 mitomycin Tray for defined disposal in the Chemotherapy Waste Bag provided.
- Stability
- Lyophilized mitomycin stored at controlled room temperature (i.e., 20 - 25C 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.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Mitomycin (topical) in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Mitomycin (topical) in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Mitomycin (topical) in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Mitomycin (topical) in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Mitomycin (topical) in pediatric patients.

# Contraindications
- Hypersensitivity
- Mitomycin is contraindicated in patients that have demonstrated a hypersensitivity to mitomycin in the past.

# Warnings
- 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.
- Hypotony
- The use of mitomycin has been associated with an increased instance of post-operative hypotony.
- Cataract Formation
- Use in phakic patients has been correlated to a higher instance of lenticular change and cataract formation.

# Adverse Reactions

## Clinical Trials Experience
- Ophthalmic Adverse Reactions
- The most frequent adverse reactions to mitomycin 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
- 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.

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Mitomycin (topical) in the drug label.

# Drug Interactions
There is limited information regarding Mitomycin (topical) Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): X
- Pregnancy Category X
- Pregnant women
- Mitomycin 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. Mitomycin 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
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mitomycin (topical) in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Mitomycin (topical) during labor and delivery.

### Nursing Mothers
- It 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 mitomycin, 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 mitomycin not breast feed because of the potential for serious adverse reactions in nursing infants.

### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.

### Geriatic Use
- No overall differences in safety and effectiveness have been observed between elderly and younger patients.

### Gender
There is no FDA guidance on the use of Mitomycin (topical) with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Mitomycin (topical) with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Mitomycin (topical) in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Mitomycin (topical) in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Mitomycin (topical) in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Mitomycin (topical) in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Topical

### Monitoring
There is limited information regarding Monitoring of Mitomycin (topical) in the drug label.

# IV Compatibility
There is limited information regarding IV Compatibility of Mitomycin (topical) in the drug label.

# Overdosage
There is limited information regarding Chronic Overdose of Mitomycin (topical) in the drug label.

# Pharmacology

## Mechanism of Action
- Mitomycin 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.

## Structure
- 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 C15H18N405 and a molecular weight of 334.33. Its chemical name is 7-amino-9-methoxymitosane and it has the following structural formula:
- Mitomycin is a sterile lyophiliized mixture of mitomycin and mannitol, which, when reconstituted with Sterile Water for Injection, provides a solution for application in glaucoma filtration surgery. Mitomycin 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.

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Mitomycin (topical) in the drug label.

## Pharmacokinetics
- Absorption
- The systemic exposure of mitomycin following ocular administration of mitomycin 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.
- 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 relatively low doses, the percent of a dose excreted in urine increases.

## Nonclinical Toxicology
- Carcinogenesis, Mutagenesis, Impairment of Fertility
- Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with mitomycin. 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 mitomycin on fertility is unknown.

# 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
- mitomycin (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 mLTB 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 (NDC49771-002-03).
- Storage
- Store kits at 20 - 25 C (68 - 77 F). Protect from light.
- Handling Procedures
- Procedures for Proper Handling and Disposal of anti-cancer drugs should be followed. Appropriate containment and disposal devices are included within the mitomycin (mitomycin for solution) Kit for Ophthalmic Use.

## Storage
There is limited information regarding Mitomycin (topical) Storage in the drug label.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
- Instruct patients to discuss with their physician if they are pregnant or if they might become pregnant
- Instruct patients to discuss with their physician if they have demonstrated a hypersensitivity to mitomycin in the past .
- Nursing mothers should be advised that it is not known if mitomycin 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, a decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the importance of the drug to the mother. It is recommended that women receiving mitomycin not breast feed because of the potential for serious adverse reactions in nursing infants .
- Patients should be advised of the toxicity of mitomycin and potential complications.

# Precautions with Alcohol
- Alcohol-Mitomycin (topical) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
MITOSOL

# Look-Alike Drug Names
There is limited information regarding Mitomycin (topical) Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price