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BRYMONT 2 MG/ML EYE DROPS SOLUTION

Active substance(s): BRIMONIDINE TARTRATE / BRIMONIDINE TARTRATE / BRIMONIDINE TARTRATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Brymont 2 mg/ml eye drops, solution

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml solution contains 2.0 mg brimonidine tartrate, equivalent to 1.3 mg of
brimonidine.
Contains benzalkonium chloride 0.05 mg/ml.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Eye drops, solution.
Clear, greenish-yellow to light greenish-yellow solution.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Reduction of elevated intraocular pressure (IOP) in patients with open angle
glaucoma or ocular hypertension.
− As monotherapy in patients in whom topical beta-blocker therapy is
contraindicated.
− As adjunctive therapy to other intraocular pressure lowering medications when the
target IOP is not achieved with a single agent (see Section 5.1).

4.2

Posology and method of administration

Posology
Recommended dosage in adults (including the elderly)
The recommended dose is one drop of Brymont in the affected eye(s) twice daily,
approximately 12 hours apart. No dosage adjustment is required for the use in elderly
patients.
Paediatric population

No clinical studies have been performed in adolescents (12 to 17 years).
Brymont is not recommended for use in children below 12 years and is
contraindicated in neonates and infants (see sections 4.3, 4.4 and 4.9). It is known that
severe adverse reactions can occur in neonates. The safety and efficacy of Brymont
have not been established in children.
Use in renal and hepatic impairment
Brymont should be used with caution in patients with hepatic or renal impairment (see
section 4.4).
Method of administration
As with any eye drops, to reduce possible systemic absorption, it is recommended that
the lacrimal sac be compressed at the medial canthus (punctal occlusion) for one
minute. This should be performed immediately following the instillation of each drop.
If more than one topical ophthalmic drug is to be used, the different drugs should be
instilled 5-15 minutes apart.

4.3

Contraindications

− Hypersensitivity to the active substance or to any of the excipients listed in section
6.1.
− Neonates and infants (see section 4.8).
− Patients receiving monoamine oxidase (MAO) inhibitor therapy and patients on
antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants
and mianserin).
4.4
Special warnings and precautions for use
Paediatric population
Children of 2 years of age and above, especially those in the 2-7 age range and/or
weighing < 20 Kg, should be treated with caution and closely monitored due to the
high incidence of somnolence (see section 4.8).
Caution should be exercised in treating patients with severe or unstable and
uncontrolled cardiovascular disease.
Some (12.7%) patients in clinical trials experienced an ocular allergic type reaction
with Brymont (see section 4.8 for details). If allergic reactions are observed,
treatment with Brymont should be discontinued.
Brymont should be used with caution in patients with depression, cerebral or coronary
insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangiitis
obliterans.
Brymont has not been studied in patients with hepatic or renal impairment; caution
should be used in treating such patients.
The preservative in Brymont, benzalkonium chloride, may cause eye irritation. Avoid
contact with soft contact lenses. Remove contact lenses prior to application and wait
at least 15 minutes before reinsertion. Known to discolour soft contact lenses.

4.5

Interaction with other medicinal products and other forms of interaction

Although specific drug interactions studies have not been conducted with Brymont,
the possibility of an additive or potentiating effect with CNS depressants (alcohol,
barbiturates, opiates, sedatives, or anaesthetics) should be considered.
No data on the level of circulating catecholamines after Brymont administration are
available. Caution, however, is advised in patients taking medications which can
affect the metabolism and uptake of circulating amines e.g. tricyclic antidepressants,
monoamine oxidase inhibitors, venlafaxine, chlorpromazine, methylphenidate,
reserpine.
After the application of Brymont, clinically insignificant decreases in blood pressure
were noted in some patients. Caution is advised when using drugs such as
antihypertensives and/or cardiac glycosides concomitantly with Brymont.
Caution is advised when initiating (or changing the dose of) a concomitant systemic
agent (irrespective of pharmaceutical form) which may interact with α-adrenergic
agonists or interfere with their activity i.e. agonists or antagonists of the adrenergic
receptor e.g. (isoprenaline, prazosin).
4.6

Fertility, pregnancy and lactation

The safety of use during human pregnancy has not been established. In animal studies,
brimonidine tartrate did not cause any teratogenic effects. In rabbits, brimonidine
tartrate, at plasma levels higher than are achieved during therapy in humans, has been
shown to cause increased preimplantation loss and postnatal growth reduction.
Brymont should be used during pregnancy only if the potential benefit to the mother
outweighs the potential risk to the foetus.
It is not known if brimonidine is excreted in human milk. The compound is excreted
in the milk of the lactating rat. Brymont should not be used by women nursing
infants.
4.7

Effects on ability to drive and use machines
Brymont may cause fatigue and/or drowsiness, which may impair the ability to drive
or operate machinery. Brymont may cause blurred and/or abnormal vision, which
may impair the ability to drive or to use machinery, especially at night or in reduced
lighting. The patient should wait until these symptoms have cleared before driving or
using machinery.

4.8

Undesirable effects

Paediatric population
In a 3-month, phase 3 study in children aged 2-7 years with glaucoma, inadequately
controlled by beta-blockers, a high prevalence of somnolence (55%) was reported
with brimonidine as adjunctive treatment. In 8% of children, this was severe and led

to discontinuation of treatment in 13%. The incidence of somnolence decreased with
increasing age, being least in the 7-year-old age group (25%), but was more affected
by weight, occurring more frequently in those children weighing 20 kg (63%)
compared to those weighing >20 kg (25%) (see section 4.4).

The most commonly reported ADRs are oral dryness, ocular hyperaemia and
burning/stinging, all occurring in 22 to 25% of patients. They are usually transient and
not commonly of a severity requiring discontinuation of treatment.
Symptoms of ocular allergic reactions occurred in 12.7% of subjects (causing
withdrawal in 11.5% of subjects) in clinical trials with the onset between 3 and 9
months in the majority of patients.
Within each frequency grouping, undesirable effects are presented in order of
decreasing seriousness. The following terminologies have been used in order to
classify the occurrence of undesirable effects: Very Common ( 1/10); Common
( 1/100 to <1/10); Uncommon ( 1/1,000 to <1/100); Rare ( 1/10,000 to <1/1,000);
Very rare (<1/10,000), not known (cannot be estimated from the available data).

Cardiac disorders
Uncommon: palpitations/arrhythmias (including bradycardia and tachycardia)
Nervous system disorders
Very common: headache, drowsiness
Common: dizziness, abnormal taste
Very rare: syncope
Eye disorders
Very common:
− ocular irritation including allergic reactions (hyperaemia, burning and stinging,
pruritus, foreign body sensation, conjunctival follicles)
− blurred vision
Common:
− local irritation (eyelid hyperaemia and oedema, blepharitis, conjunctival oedema
and discharge, ocular pain and tearing)
− photophobia
− corneal erosion and staining
− ocular dryness
− conjunctival blanching
− abnormal vision
− conjunctivitis
Very rare:
− iritis (anterior uveitis)
− miosis

Respiratory, thoracic and mediastinal disorders
Common: upper respiratory symptoms
Uncommon: nasal dryness
Rare: dyspnoea
Gastrointestinal disorders
Very common: oral dryness
Common: gastrointestinal symptoms
Vascular disorders
Very rare: hypertension, hypotension
General disorders and administration site conditions
Very common: fatigue
Common: asthenia
Immune system disorders
Uncommon: systemic allergic reactions
Psychiatric disorders
Uncommon: depression
Very rare: insomnia
In cases where brimonidine has been used as part of the medical treatment of
congenital glaucoma, symptoms of brimonidine overdose such as loss of
consciousness, hypotension, hypotonia, bradycardia, hypothermia, cyanosis and
apnoea have been reported in neonates and infants receiving brimonidine (see section
4.3).

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 Yellow Card Scheme website: www.mhra.gov.uk/yellowcard

4.9

Overdose

Ophthalmic overdose
Paediatric population

Symptoms of brimonidine overdose (including loss of consciousness, hypotension,
hypotonia, bradycardia, hypothermia, cyanosis and apnoea) have been reported in
neonates and infants receiving as part of medical treatment of congenital glaucoma.
There is no experience in adults with the unlikely case of an overdosage via the
ophthalmic route.
Systemic overdose resulting from accidental ingestion:
Paediatric population
Reports of serious adverse effects following inadvertent ingestion of brimonidine by
paediatric subjects have been published or reported to Allergan. The subjects
experienced symptoms of CNS depression, typically temporary coma or low level of
consciousness, hypotonia, bradycardia, hypothermia and apnoea, and required
admission to intensive care with intubation if indicated. All subjects were reported to
have made a full recovery, usually within 6-24 hours.
Two cases of adverse effects following inadvertent ingestion of 9-10 drops of
brimonidine by adult subjects have been received. The subjects experienced a
hypotensive episode, followed in one instance by rebound hypertension
approximately 8 hours after ingestion. Both subjects were reported to have made a full
recovery within 24 hours. No adverse effects were noted in a third subject who also
ingested an unknown amount of Brymont orally.
Oral overdoses of other alpha-2-agonists have been reported to cause symptoms such
as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias,
miosis, apnoea, hypotonia, hypothermia, respiratory depression and seizure.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Sympathomimetics in glaucoma therapy, ATC code =
S01EA 05.
Brimonidine is an alpha-2 adrenergic receptor agonist that is 1000-fold more selective
for the alpha-2 adrenoceptor than the alpha-1 adrenoreceptor. This selectivity results
in no mydriasis and the absence of vasoconstriction in microvessels associated with
human retinal xenografts.
Topical administration of brimonidine tartrate decreases intraocular pressure (IOP) in
humans with minimal effect on cardiovascular or pulmonary parameters.
Limited data are available for patients with bronchial asthma showing no adverse
effects.
Brymont has a rapid onset of action, with peak ocular hypotensive effect seen at two
hours post-dosing. In two 1 year studies, Brymont lowered IOP by mean values of
approximately 4-6 mmHg.

Fluorophotometric studies in animals and humans suggest that brimonidine tartrate
has a dual mechanism of action. It is thought that Brymont may lower IOP by
reducing aqueous humour formation and enhancing uveoscleral outflow.
Clinical trials show that Brymont is effective in combination with topical betablockers. Shorter term studies also suggest that Brymont has a clinically relevant
additive effect in combination with travoprost (6 weeks) and latanoprost (3 months).

5.2

Pharmacokinetic properties

Absorption
Following oral administration to man, brimonidine is well absorbed.
After ocular administration of a 0.2% solution twice daily for 10 days, plasma
concentrations were low (mean Cmax was 0.06 ng/ml). There was a slight
accumulation in the blood after multiple (2 times daily for 10 days) instillations. The
area under the plasma concentration-time curve over 12 hours at steady state (AUC012h) was 0.31 ng·hr/ml, as compared to 0.23 ng·hr/ml after the first dose. The mean
apparent half-life in the systemic circulation was approximately 3 hours in humans
after topical dosing.
Distribution
The plasma protein binding of brimonidine after topical dosing in humans is
approximately 29%.
Brimonidine binds reversibly to melanin in ocular tissues, in vitro and in vivo.
Following 2 weeks of ocular instillation, the concentrations of brimonidine in iris,
ciliary body and choroid-retina were 3- to 17-fold higher than those after a single
dose. Accumulation does not occur in the absence of melanin.
The significance of melanin binding in humans is unclear. However, no significant
ocular adverse reaction was found during biomicroscopic examination of eyes in
patients treated with Brymont for up to one year, nor was significant ocular toxicity
found during a one year ocular safety study in monkeys given approximately four
times the recommended dose of brimonidine tartrate.
Biotransformation and Elimination
Following oral administration to man, brimonidine is rapidly eliminated. The major
part of the dose (around 75% of the dose) was excreted as metabolites in urine within
five days; no unchanged drug was detected in urine. In vitro studies, using animal and
human liver, indicate that the metabolism is mediated largely by aldehyde oxidase and
cytochrome P450. Hence, the systemic elimination seems to be primarily hepatic
metabolism.
Linearity/Non-linearity
No great deviation from dose proportionality for plasma Cmax and AUC was
observed following a single topical dose of 0.08%, 0.2% and 0.5%.

The Cmax, AUC, and apparent half-life of brimonidine are similar in the elderly
(subjects 65 years or older)after a single dose compared with young adults, indicating
that its systemic absorption and elimination are not affected by age.
Based on data from a 3 month clinical study, which included elderly patients,
systemic exposure to brimonidine was very low.
5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies
of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential,
and toxicity to reproduction.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Benzalkonium Chloride
Poly(vinyl alcohol)
Sodium chloride
Sodium citrate
Citric acid monohydrate
Water for Injection
Hydrochloric acid for pH-adjustment or
Sodium hydroxide for pH-adjustment

6.2

Incompatibilities
Not applicable.

6.3

Shelf life

Before first opening: 3 years.
After first opening: Use within 28 days.
6.4

Special precautions for storage

Do not store above 25°C.
Keep bottle in the outer carton in order to protect from light
For storage conditions after first opening of the medicinal product, see section 6.3.

6.5

Nature and contents of container

White plastic (LDPE) bottle with a transparent plastic dropper (LDPE) and a white
plastic screw cap (HDPE) containing 5 ml of a clear greenish-yellow to light greenishyellow solution.
5 ml plastic bottles in packs of 1, 2 or 3.
Not all pack sizes may be marketed.
6.6

Special precautions for disposal
No special requirements.
Any unused product or waste material should be disposed of in accordance with local
requirements

7

MARKETING AUTHORISATION HOLDER
Blumont Pharma Ltd
23 Moortown Close
Grantham
Lincs
NG31 9GG

8

MARKETING AUTHORISATION NUMBER(S)
PL 31103/0004

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
13/04/2010

10

DATE OF REVISION OF THE TEXT
17/02/2016

Expand Transcript

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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