MAXITROL OINTMENT

Active substance: POLYMYXIN B SULPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS
1.

NAME OF THE MEDICINAL PRODUCT
MAXITROL ointment

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
1 gram ointment contains 1 mg dexamethasone , 6000 IU polymyxin B
sulphate, and 3500 IU neomycin sulphate (as base).
For a full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM
Eye ointment
White to very pale yellow homogeneous translucent ointment

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
MAXITROL eye ointment is indicated for the short-term treatment of steroid
responsive conditions of the eye when prophylactic antibiotic treatment is also
required, after excluding the presence of fungal and viral disease.

4.2

Posology and method of administration
Children and Adults (including the Elderly)
Apply a small amount into the conjunctival sac(s) up to three to four times daily or,
may be used adjunctively with drops at bedtime.

4.3

Contraindications






4.4

Hypersensitivity to the active substances or to any of the excipients.
Herpes simplex keratitis.
Vaccinia, varicella, and other viral infection of cornea or conjunctiva.
Fungal diseases of ocular structures.
Mycobacterial ocular infections.

Special warnings and precautions for use



For topical ophthalmic use only. Not for injection or ingestion.



As with all antibacterial preparation prolonged use may lead to overgrowth of
non-susceptible bacterial strains or fungi. If superinfection occurs, appropriate
therapy should be initiated.
Sensitivity to topically applied aminoglycosides may occur in some patients.
Cross-sensitivity to other aminoglycosides may also occur. If signs of serious
reactions or hypersensitivity occur, discontinue use of MAXITROL eye
ointment.
Patients using ophthalmic preparations containing neomycin sulphate should be
advised to consult a physician if ocular pain, redness, swelling, or irritation
worsens or persists.
Serious adverse reactions including neurotoxicity, ototoxicity and nephrotoxicity
have occurred in patients receiving systemic neomycin or when applied topically
to open wounds or damaged skin. Nephrotoxic and neurotoxic reactions have
also occurred with systemic polymyxin B. Although these effects have not been
reported following topical ocular use of this product, caution is advised when
used concomitantly with systemic aminoglycoside or polymyxin B therapy.
Prolonged use of ophthalmic use may result in ocular hypertension and/or
glaucoma, with damage to the optic nerve, reduced visual acuity and visual field
defects, and posterior subcapsular cataract formation. In patients receiving
prolonged ophthalmic corticosteroid therapy, intraocular pressure should be
checked routinely and frequently. This is especially important in paediatric
patients, as the risk of corticosteroid induced ocular hypertension may be greater
in children and may occur earlier than in adults.
In those diseases causing thinning of the cornea or sclera, perforations have been
known to occur with the use of topical corticosteroids.
Corticosteroids may reduce resistance to and aid in the establishment of nonsusceptible bacterial, viral, or fungal infections and mask the clinical signs of
infection, or may suppress hypersensitivity reactions to substances in the
product. Fungal infection should be suspected in patients with persistent corneal
ulceration who have been or are receiving these drugs and corticosteroid therapy
should be discontinued if fungal infection occurs.
To avoid the risk of enhancement of herpetic corneal disease, frequent slip lamp
examination is essential.
Contact lens wear is discouraged during treatment of an ocular infection.
Therefore patients should be advised not to wear contact lenses during treatment
with MAXITROL eye ointment.
This
product
contains
methylparahydroxybenzoate
and
propylparahydroxybenzoate which may cause allergic reactions (possibly
delayed).
This product also contains lanolin which may cause local skin reactions (e.g.
contact dermatitis).



















4.5

Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.
No clinically relevant interactions have been described with MAXITROL eye
ointment.
Concomitant and/or sequential use of an aminoglycoside (neomycin) and other
systemic, oral, or topical drugs that have neurotoxic, ototoxic, or nephrotoxic effects
may result in additive toxicity and should be avoided, whenever possible.
If more than one ophthalmic medicinal product is being used, the medicines must be
administered at least 5 minutes apart. Eye ointments should be administered last.

4.6

Fertility, pregnancy and lactation
Fertility
There are no data available on the use of this medicine affecting male or female
fertility.
Pregnancy
There are no or limited amount of data from the use of MAXITROL eye ointment in
pregnant women. Studies in animals with some active components of MAXITROL
eye ointment have shown reproductive toxicity (see section 5.3).
MAXITROL eye ointment is not recommended during pregnancy.
Lactation
It is unknown whether topical ophthalmic dexamethasone, neomycin or polymyxin B
are excreted in human milk. Because systemic corticosteroids and aminoglycosides may
be distributed into milk, a risk to the suckling child cannot be excluded.
A decision on whether to discontinue/abstain from breast-feeding or to discontinue
therapy with MAXITROL eye ointment taking into account the benefit of breastfeeding for the child and the benefit of the product to the woman.

4.7

Effects on Ability to Drive and Use Machines

MAXITROL eye ointment has no or negligible influence on the ability
to drive and use machines. As with any other eye drop, temporarily
blurred vision or other visual disturbances may affect the ability to
drive or use machines. If transient blurred vision occurs upon
instillation, the patient must wait until the vision clears before driving
or using machinery.

Undesirable effects
In clinical trials with MAXITROL eye drops and MAXITROL eye ointment the most
common adverse reactions were ocular discomfort, keratitis and eye irritation,
occurring in 0.7% to 0.9% of patients.
Tabulated summary of adverse reactions
The following adverse reactions are classified according to the following convention:
very common ( 1/10), common ( 1/100 to <1/10), uncommon ( 1/1,000 to <1/100),
rare ( 1/10,000 to <1/1000), very rare (<1/10,000) or not known (cannot be estimated
from the available data). Within each frequency grouping, adverse reactions are
presented in decreasing order of seriousness. The adverse reactions were obtained from
clinical trials and post-marketing experience.
System Organ Classification
MedDRA
Preferred
Term
(v.13.1)
Immune system disorders
Uncommon: hypersensitivity
(systemic or ocular)
Nervous system disorders
Not known: headache
Eye disorders
Uncommon: keratitis, intraocular
pressure increased, vision-blurred,
photophobia, mydriasis, eyelid
ptosis, eye pain, eye swelling, eye
pruritus, ocular discomfort,
foreign body sensation in eyes, eye
irritation, ocular hyperaemia,
increased lacrimation









4.8

Not known: corneal thinning
Description of selected adverse event
Due to the steroid component, in diseases causing thinning of the cornea or sclera
there is a higher risk for perforation especially after long treatments (See Section
Special warnings and precautions for use).
Topical ophthalmic steroid use may result in increased intraocular pressure with
damage to the optic nerve, reduced visual acuity and visual field defects. Also it may
lead to posterior subcapsular cataract formation (See Section Special warnings and
precautions for use).
Sensitivity to topically administered aminoglycosides may occur in some patients
(See Section Special warnings and precautions for use). Systemic side effects may
occur with extensive use.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal

product. Healthcare professionals are asked to report any suspected adverse reactions
via the national reporting system:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard

4.9

Overdose
No case of overdose has been reported.
Signs and symptoms of an overdosage of MAXITROL eye ointment may be similar
to adverse reaction effects seen in some patients (punctuate keratitis, erythema,
increased lacrimation, oedema and lid itching).
Due to the characteristics of this preparation, intended for topical use, no toxic
effects are expected when administered to the eye neither at the recommended dose
nor in the event of accidental ingestion of the contents of a bottle.
A topical ophthalmic overdose of MAXITROL eye ointment may be flushed from the
eye(s) with lukewarm water.

5.

PHARMACOLOGICAL PROPERTIES
5.1

Pharmacodynamic Properties

Pharmacotherapeutic group: ophthalmologicals; anti-infectives
ATC code: S01CA01
Mechanism of Action
MAXITROL eye ointment has a dual effect: suppression of inflammation
symptoms by the corticosteroidal component dexamethasone, and an
anti-infective effect due to the presence of two antibiotics, polymyxin B and
neomycin.
Dexamethasone is a synthetic glucorticoid with potent anti-inflammatory
activity. Polymyxin B is a cyclic lipopeptide that penetrates the cell wall of
gram-negative bacilli to destabilize the cytoplasmic membrane. It is generally
less active against gram-positive bacteria. Neomycin is an aminoglycoside
antibiotic that primarily exerts its effect on bacterial cells by inhibiting
polypeptide assembly and synthesis on the ribosome.
Mechanism of Resistance
Resistance of bacteria to polymyxin B is of chromosomal origin and is
uncommon. A modification of the phospholipids of the cytoplasmic membrane
appears to play a role.

Resistance to neomycin occurs by several different mechanisms including (1)
alterations of the ribosomal subunit within the bacterial cell; (2) interference
with the transport of neomycin into the cell, and (3) inactivation by an array of
adenylating, phosphorylating, and acetylating enzymes. Genetic information
for production of inactivating enzymes may be carried on the bacterial
chromosome or on plasmids.
Breakpoints
Each gram of MAXITROL eye ointment contains 6000 IU polymyxin B
sulphate and 3500 IU neomycin sulphate. The breakpoints and the in vitro
spectrum as mentioned below are based on the dual activity of either
polymyxin B or neomycin. The breakpoints listed here are based upon
acquired resistance for specific species found in ocular infections and the ratio
in International Units of polymyxin B to neomycin in MAXITROL eye
ointment:
Resistance breakpoints: >5:2.5 to >40:20 depending upon the bacterial species
Susceptibility
The information listed below provides guidance on the approximate
probabilities on the susceptibility of microorganisms to polymyxin B or
neomycin in MAXITROL eye ointment. The presentation below lists bacterial
species recovered from external ocular infections of the eye.
The prevalence of acquired resistance may vary geographically and with time
for selected species and local information on resistance is desirable,
particularly when treating severe infections. As necessary, expert advice
should be sought when the local prevalence of resistance is such that the utility
of the combination of polymyxin B or neomycin as in MAXITROL eye
ointment in at least some types of infections is questionable.
COMMONLY SUSCEPTIBLE SPECIES
Aerobic Gram-positive microorganisms
Bacillus cereus
Bacillus megaterium
Bacillus pumilus
Bacillus simplex
Corynebacterium accolens
Corynebacterium bovis
Corynebacterium macginleyi
Corynebacterium propinquum
Corynebacterium pseudodiphtheriticum
Staphylococcus aureus (methicillin susceptible - MSSA)
Staphylococcus capitis
Staphylococcus epidermidis (methicillin susceptible - MSSE)
Staphylococcus pasteuri
Staphylococcus warneri
Streptococcus mutans

Aerobic Gram-negative microorganisms
Haemophilus influenzae
Klebsiella pneumoniae
Moraxella catarrhalis
Moraxella lacunata
Pseudomonas aeruginosa
Serratia species
SPECIES FOR WHICH ACQUIRED RESISTANCE MIGHT BE A PROBLEM
Staphylococcus epidermidis (methicillin resistant - MRSE)
Staphylococcus hominis
Staphylococcus lugdunensis

INHERENTLY RESISTANT ORGANISMS
Aerobic Gram-positive microorganisms
Enterococci faecalis
Staphylococcus aureus (methicillin resistant - MRSA)
Streptococcus mitis
Streptococcus pneumoniae
Anaerobic Bacteria
Propionibacterium acnes

Dexamethasone is a moderately powerful corticosteroid having good
penetration in ocular tissue. Corticosteroids have an anti-inflammatory as
well as a vasoconstrictive effect. They suppress the inflammatory response
and symptoms in various disorders without basically curing these
disorders.

5.2.

Pharmacokinetic Properties
Dexamethasone, like other corticosteroids, is absorbed rapidly after oral
administration and has a biological half-life of about 190 minutes. Sufficient
absorption may occur after topical application to the skin and eye to produce
systemic effects. Intraocular penetration of dexamethasone occurs in significant
amounts and contributes to the effectiveness of dexamethasone in anterior segment
inflammatory disease.
Polymyxin B sulphate is not absorbed from the gastrointestinal tract or through intact
skin, although the intact corneal epithelium prevents penetration into the corneal
stroma, therapeutic concentrations do enter the stroma after epithelial damage. Good
stromal penetration occurs after epithelial abrasion following topical instillation,
subconjunctival injection, or corneal bath. No significant polymyxin B penetration
into the vitreous is demonstrable after parenteral or local administration of the drug.
Neomycin is poorly absorbed from the gastrointestinal tract and after topical

administration an insufficient amount is absorbed to produce systemic effects.
Absorption has been reported to occur from wounds and inflamed skin. After
absorption neomycin is rapidly excreted by the kidneys in active form.

5.3

Preclinical Safety Data
Mutagenicity and Carcinogenicity
Genotoxicity studies performed with neomycin and polymyxin B, with and
without metabolic activation, were negative in bacterial (Ames test) or
mammalian cells (chromosomal aberration assay in CHO cells).
Dexamethasone was clastogenic in vivo in the mouse micronucleus assay at
doses in excess of those obtained following topical application. Conventional
long term carcinogenicity studies with MAXITROL or its active constituents
have not been performed.
Teratogenicity
Pregnant rats treated daily with high doses of neomycin produced offspring that
exhibited significant ototoxicity. The teratogenic dose is far greater (> 10,000fold) than the clinical daily exposure from MAXITROL. Dexamethasone has
been found to be teratogenic in animal models. Dexamethasone induced
abnormalities of foetal development including cleft palate, intra-uterine growth
retardation and affects on brain growth and development.
Local Tolerance and Systemic Effects
Systemic exposure to dexamethasone is associated with its pharmacological
effects as a potent glucocorticoid. Prolonged exposure to the steroid can result
in glucocorticoid imbalance. Topical ocular safety studies with dexamethasone
in rabbits have shown systemic effects after 1 month of treatment. In rabbits,
MAXITROL was shown to have minimal irritation potential after
administration to either control or irritated eyes.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Methylparaben
Propylparaben
Liquid lanolin
Petrolatum

6.2.

Incompatibilities
None known.

6.3

Shelf Life
48 months
Discard 28 days after first opening

6.4.

Special Precautions for Storage
Do not store above 25°C. Keep away from direct sunlight. Do not refrigerate. Keep
the container tightly closed.

6.5.

Nature and Content of Container
3.5 g metal tube with nozzle and screw cap.

6.6

Special precautions for disposal and other handling
Do not touch the top of the tube to any surface as this may contaminate
the contents.
Any unused product or waste material should be disposed of in
accordance with local requirements.

7

MARKETING AUTHORISATION HOLDER
Alcon Laboratories (UK) Ltd
Frimley Business Park,
Frimley, Camberley,
Surrey, GU16 7SR
United Kingdom.

8.

MARKETING AUTHORISATION NUMBER
PL 00649/5916R

9.

DATE OF FIRST AUTHORISATION / RENEWAL OF AUTHORISATION
18 January 1991

10

DATE OF REVISION OF THE TEXT

07/01/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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