MAXITROL EYE DROPS

Active substance: POLYMYXIN B SULPHATE

View full screen / Print PDF » Download PDF ⇩

Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
MAXITROL EYE DROPS

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml suspension contains 1 mg dexamethasone, 6000 IU polymyxin B
sulphate, 3500 IU neomycin sulphate (as base)
Excipients: 1 ml suspension contains 0.04 mg benzalkonium chloride
For a full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM
Eye drops, suspension
White sterile suspension for topical ocular administration.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
MAXITROL eye drops, suspension 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 one or two drops to each affected eye up to six times daily or, more
frequently if required.

4.3

Contraindications
• Hypersensitivity to the active substances or to any component of
the preparation.






4.4

Epithelial herpes simplex keratitis.
Vaccinia, varicella, or other viral infection of cornea and
conjunctiva (except herpes zoster keratitis).
Fungal disease s of ocular structures.
Mycobacterial ocular infections.

Special Warning and Special Precautions for Use
• For ocular 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 the use of this product.
• 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 steroids 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.
• 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
bacterial, viral, or fungal infections and mask the clinical signs of infection,
preventing recognition of ineffectiveness of the antibiotic, or may suppress
hypersensitivity reactions to MAXITROL eye drops, suspension. Fungal
infection should be suspected in patients with persistent corneal ulceration
who have been or are receiving these drugs; corticosteroid therapy should be
discontinued if fungal infection occurs.
• To avoid the risk of enhancement of herpetic corneal disease, frequent slit
lamp examination is essential.
• Contact lens wear is not recommended during treatment of an ocular
infection. Therefore patients should be advised not to wear contact lenses
during treatment with MAXITROL eye drops, suspension.
• MAXITROL eye drops, suspension contains benzalkonium chloride which
may cause eye irritation and is known to discolour soft contact lenses.
Patients must be instructed to remove contact lenses prior to application of

MAXITROL eye drops, suspension and wait 15 minutes after instillation of
the dose before reinsertion.
4.5

Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
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.

4.6

Pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of MAXITROL eye
drops, suspension in pregnant women. Studies in animals with some active
components of MAXITROL eye drops, suspension have shown reproductive
toxicity (see section 5.3).
MAXITROL eye drops, suspension 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 must be made whether to discontinue breast-feeding or to
discontinue therapy with MAXITROL eye drops, suspension taking into
account the benefit of breast-feeding for the child and the benefit of the
product to the woman.
4.7

Effects on Ability to Drive and Use Machines
MAXITROL eye drops, suspension 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.

4.8

Undesirable Effects

Tabulated summary of adverse reactions

The following adverse effects 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, undesirable effects are presented in decreasing order of seriousness.
The adverse reactions were obtained from clinical trials and postmarketing
spontaneous reports.
System Organ Classification
Immune system disorders

MedDRA Preferred Term (v.12.0)
Not known: hypersensitivity (systemic
or ocular)

Nervous system disorders

Not known: headache

Eye disorders

Uncommon: keratitis, intraocular
pressure increased, eye irritation, eye
pruritus, ocular discomfort

Not known: corneal thinning,
photophobia, blurred vision, mydriasis,
eye pain, eye swelling, ptosis, foreign
body sensation in eyes, increased
lacrimation, ocular hyperaemia

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.
4.9

Overdose
No case of overdose has been reported.
Signs and symptoms of an overdosage of MAXITROL eye drops,
suspension may be similar to adverse reaction effects seen in some
patients (punctuate keratitis, erythema, increased lacrimation, oedema
and lid itching).

A topical ophthalmic overdose of MAXITROL eye drops, suspension
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 drops, suspension 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 drops, suspension 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 drops,
suspension:
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 drops, suspension. 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 drops,
suspension 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 (>
10,000-fold) 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
Sodium chloride
Polysorbate 20
Benzalkonium chloride
Hydroxypropyl methylcellulose
Hydrochloric acid/sodium hydroxide
Purified water

6.2.

Incompatibilities
None known.

6.3

Shelf Life
Unopened 24 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 Contents of Container
5 ml & 10 ml DROP-TANIER, natural LDPE bottles and plugs with
polystyrene or polypropylene caps.

6.6

Special precautions for disposal and other handling

Do not touch the tip of the bottle 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 0649/5915R

9.
DATE OF FIRST AUTHORISATION / RENEWAL OF
AUTHORISATION
24 January 1991

10

DATE OF REVISION OF THE TEXT
13/08/2013

Expand view ⇕

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.

Hide
(web4)