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
1. G
ettin
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arte
d
N
on-S
teril
e C
ircul
atin
g N
urse
:
Ster
ile S
urgi
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echn
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n:
2. R
econ
stitu
ting
Mito
sol®
a.
Scr
ew w
hite
plu
nger
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to ru
bber
plu
nger
of p
re-fi
lled
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Fig.
1)
b.
Pre
ss fi
rmly
and
scr
ew th
e bl
ue e
ndbl
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nd
o
f the
syr
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con
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Fig.
2)
with
alc
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p pa
d.
lid
until
sea
ted
and
secu
re. (
Fig.
3)
(Fig
. 4)
®.
If pr
oduc
t
Ref
eren
ce ID
: 308
3781
3. P
repa
ring
spon
ges
a.
Inve
rt v
ial a
nd s
yrin
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(Fig
. 6)
d.
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ner t
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Mito
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with
in 1
hou
r of r
econ
stitu
tion:
Mito
sol®
(Fig
. 7)
fluid
/air
into
syr
inge
.
Ref
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ce ID
: 308
3781
4. U
sing
Mito
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to th
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ite. (
Fig.
8)
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DIS
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22 R
ev. D
Ref
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ce ID
: 308
3781
Checked by Approved by
Department Design Studio Marketing Packing Dev. Q.A. Q.A.
Signature
Date
100 %
250 %
Varn
ish fr
ee ar
ea8 x
18 m
m
NDC 49771-002-02
Mitosol®
(mitomycin for solution)0.2 mg/vial
Lyophilized Mitomycin forreconstitution
Protect from light.Single Use Vial
Dose: See Package Insert.Rx Only
Manu
factur
ed fo
r:Mo
bius T
herap
eutic
s LLC
St. L
ouis
MO
6310
8 US
AMa
nufac
tured
by:
Intas
Pha
rmac
eutic
als Lt
d.Ah
meda
bad –
382 2
10, IN
DIA.
Mfg.
Lic. N
o. : G
/1026
10 97
50 1
6357
79
Stor
e at 2
0–2
5C
(68
–77
F).
Varn
ish fr
ee ar
ea8 x
18 m
m
NDC 49771-002-02
Mitosol®
(m tomycin for solut on)0 2 mg/vial
Lyoph l zed M tomycin oreconstitu ion
Protect from ightSingle Use V al
Dose: See Package InsertRx Only
Manu
actur
ed o
r:Mo
bius T
herap
euics
LLC
St Lo
us M
O 63
108
USA
Manu
actur
ed by
:Int
as P
harm
aceu
tcals
Ld
Ahme
daba
d – 38
2 210
INDI
AMf
g Lic
No
: G/10
2610
9750
1 63
5779
Sor
e at 2
0°–2
5°C
(68°
–77°
F)
Reference ID: 3083781
(b) (4)