'Optimol 0.5%' Eye Drops Solution is a beta-adrenoreceptor blocking agent used topically in
the reduction of elevated intra-ocular pressure in various conditions including the following:
patients with ocular hypertension; patients with chronic open-angle glaucoma including
aphakic patients; some patients with secondary glaucoma.

If clinical response is not adequate, dosage may be changed to one drop 0.5% solution in
each affected eye twice a day. If needed, 'Optimol' may be used with other agent(s) for
lowering intra-ocular pressure. The use of two topical beta-adrenergic blocking agents is not
recommended (see 4.4 'Special warnings and precautions for use').
Intra-ocular pressure should be reassessed approximately four weeks after starting treatment
because response to 'Optimol' may take a few weeks to stabilise.
Provided that the intra-ocular pressure is maintained at satisfactory levels, many patients can
than be placed on once-a-day therapy.
Transfer from other agents 

When another topical beta-blocking agent is being used, discontinue its use after a full day
of therapy and start treatment with 'Optimol' the next day with one drop of 0.25% 'Optimol'
in each affected eye twice a day. The dosage may be increased to one drop of 0.5% solution
in each affected eye twice a day, if the response is not adequate.
When transferring a patient from a single anti-glaucoma agent other than a topical betablocking
agent, continue the agent and add one drop of 0.25% 'Optimol' in each affected eye
twice a day. On the following day, discontinue the previous agent completely, and continue
with 'Optimol'. If a higher dosage of 'Optimol' is required, substitute one drop of 0.5%
solution in each affected eye twice a day.
'Optimol' Eye Drops Solution is also available as 'Optimol' Unit dose: The Unit-dose
Dispenser of 'Optimol' is free from preservative and should be used for patients who may be
sensitive to the preservative benzalkonium chloride, or when use of a preservative-free
topical medication is advisable.
Paediatric use: is not currently recommended.
Use in the elderly: there has been wide experience with the use of timolol maleate in elderly
patients. The dosage recommendations given above reflect the clinical data derived from this
experience.

Like other topically applied ophthalmic drugs, 'Optimol' may be absorbed systemically and
adverse reactions seen with oral beta-blockers may occur.
Cardiac failure should be adequately controlled before beginning therapy with 'Optimol'.
Patients with a history of severe cardiac disease should be watched for signs of cardiac
failure and have their pulse rates checked.
Respiratory and cardiac reactions, including death due to bronchospasm in patients with asthma and, rarely, death associated with cardiac failure have been reported.
The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be
exaggerated when 'Optimol' is given to the patients already receiving a systemic betablocking
agent. The response of these patients should be closely observed. The use of two
topical beta-adrenergic blocking agents is not recommended.
There have been reports of skin rashes and/or dry eyes associated with the use of betaadrenoreceptor
blocking drugs. The reported incidence is small and in most cases the
symptoms have cleared when treatment was withdrawn. Discontinuation of the drug should
be considered if any such reaction is not otherwise explicable. Cessation of therapy
involving beta-blockade should be gradual.
Choroidal detachment has been reported with administration of aqueous suppressant therapy
(e.g. timolol, acetazolamide) after filtration procedures.
'Optimol' has been generally well tolerated in glaucoma patients wearing conventional hard
contact lenses. 'Optimol' has not been studied in patients wearing lenses made with material
other than polymethylmethacrylate (PMMA), which is used to make hard contact lenses.
The Ocumeter® Dispenser of 'Optimol' contains benzalkonium chloride as a preservative
which may be deposited in soft contact lenses; therefore 'Optimol' should not be used while
wearing these lenses. The lenses should be removed before application of the drops and not
reinserted earlier than 15 minutes after use. 

In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen
the angle. This requires constricting the pupil with a miotic. 'Optimol' has little or no effect
on the pupil. When 'Optimol' is used to reduce elevated intra-ocular pressure in angleclosure
glaucoma it should be used with a miotic and not alone.
Patients should be advised that if they develop an intercurrent ocular condition (e.g. trauma,
ocular surgery or infection), they should immediately seek their physician's advice
concerning the continued use of the present multidose container (see 6.6 'Special precautions
for disposal and other handling').
There have been reports of bacterial keratitis associated with the use of multiple dose
containers of topical ophthalmic products. These containers had been inadvertently
contaminated by patients who, in most cases, had a concurrent corneal disease or a
disruption of the ocular epithelial surface.
Risk from anaphylactic reaction: While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to
repeated challenge with such allergens, either accidental, diagnostic, or therapeutic. Such
patients may be unresponsive to the usual doses of epinephrine (adrenaline) used to treat
anaphylactic reactions.

Although 'Optimol' alone has little or no effect on pupil size, mydriasis has occasionally
been reported when 'Optimol' is given with epinephrine (adrenaline).
Potentiated systemic beta-blockade (e.g. decreased heart rate, depression) has been reported
during combined treatment with CYP2D6 inhibitors (e.g.quinidine, SSRIs) and timolol.
Oral β-adrenergic blocking agents may exacerbate the rebound hypertension which can
follow the withdrawal of clonidine.
'Optimol' may potentially add to the effects of oral calcium antagonists, rauwolfia alkaloids
or beta-blockers, to induce hypotension and/or marked bradycardia.
Close observation of the patient is recommended when a beta-blocker is administered to
patients receiving catecholamine-depleting drugs such as reserpine, because of possible
additive effects and the production of hypotension and/or marked bradycardia, which may
produce vertigo, syncope, or postural hypotension.
Oral calcium antagonists may be used in combination with beta-adrenergic blocking agents
when heart function is normal, but should be avoided in patients with impaired cardiac
function.
The potential exists for hypotension, AV conduction disturbances and left ventricular failure
to occur in patients receiving a beta-blocking agent when an oral calcium entry blocker is
added to the treatment regimen. The nature of any cardiovascular adverse effect tends to
depend on the type of calcium blocker used. Dihydropyridine derivatives, such as nifedipine,
may lead to hypotension, whereas verapamil or diltiazem have a greater propensity to lead to
AV conduction disturbances or left ventricular failure when used with a beta-blocker.

Intravenous calcium channel blockers should be used with caution in patients receiving betaadrenergic
blocking agents.
The concomitant use of beta-adrenergic blocking agents and digitalis with either diltiazem
or verapamil may have additive effects in prolonging AV conduction time.

Use in pregnancy: 'Optimol' has not been studied in human pregnancy. The use of 'Optimol'
requires that the anticipated benefit be weighed against possible hazards.
Breast-feeding mothers: Timolol is detectable in human milk. A decision for breast-feeding
mothers, either to stop taking 'Optimol' or stop nursing, should be based on the importance
of the drug to the mother.

Possible side effects such as dizziness and visual disturbances may affect some patients'
ability to drive or operate machinery.

Side effects
'Optimol' is usually well tolerated. The following adverse reactions have been reported with
ocular administration of this or other timolol maleate formulations, either in clinical trials or
since the drug has been marketed. Additional side effects have been reported in clinical
experiences with systemic timolol maleate, and may be considered potential effects of
ophthalmic timolol maleate:
Special senses:
ocular: signs and symptoms of ocular irritation, including burning and stinging,
conjunctivitis, blepharitis, keratitis, dry eyes and decreased corneal sensitivity. Tinnitus,
visual disturbances, including refractive changes (due to withdrawal of miotic therapy in
some cases), diplopia, ptosis and choroidal detachment following filtration surgery (see 4.4
'Special warnings and precautions for use').
Cardiovascular:
ocular: bradycardia, arrhythmia, hypotension, syncope, heart block, cerebrovascular
accident, cerebral ischaemia, congestive heart failure, palpitation, cardiac arrest, oedema,
claudication, Raynaud's phenomenon, cold hands and feet.

systemic: AV block (second- or third-degree), sino-atrial block, pulmonary oedema,
worsening of arterial insufficiency, worsening of angina pectoris, vasodilation.
Respiratory:
ocular: bronchospasm (predominantly in patients with pre-existing bronchospastic disease),
respiratory failure, dyspnoea, cough.
systemic: rales
Body as a whole:
ocular: headache, asthenia, fatigue, chest pain.
systemic: extremity pain, decreased exercise tolerance.
Integumentary:
ocular: alopecia, psoriasiform rash or exacerbation of psoriasis.
systemic: pruritus, sweating, exfoliative dermatitis.
Hypersensitivity:
ocular: signs and symptoms of allergic reactions including anaphylaxis, angioedema,
urticaria, localised and generalised rash.
Nervous system/psychiatric:
ocular: dizziness, depression, insomnia, nightmares, memory loss, increase in signs and
symptoms of myasthenia gravis, paresthesia.
systemic: vertigo, local weakness, diminished concentration, increased dreaming.
Digestive:
ocular: nausea, diarrhoea, dyspepsia, dry mouth.
systemic: vomiting 

Urogenital:
ocular: decreased libido, Peyronie's disease.
systemic: impotence, micturition difficulties.
Immunologic:
ocular: systemic lupus erythematosus
Endocrine:
systemic: hyperglycaemia, hypoglycaemia.
Musculoskeletal:
systemic: arthralgia.
Haematologic:
systemic: non-thrombocytopenic purpura.

There have been reports of inadvertent overdosage with 'Optimol' resulting in systemic
effects similar to those seen with systemic beta-adrenergic blocking agents such as
dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest (see
'Side effects').
If overdosage occurs, the following measures should be considered:
1. Gastric lavage, if ingested. Studies have shown that timolol does not dialyse readily.
2. Symptomatic bradycardia: atropine sulphate, 0.25 to 2 mg intravenously, should be used
to induce vagal blockade. If bradycardia persists, intravenous isoprenaline hydrochloride
should be administered cautiously. In refractory cases, the use of a cardiac pacemaker may
be considered.
3. Hypotension: a sympathomimetic pressor agent such as dopamine, dobutamine or noradrenaline should be used. In refractory cases, the use of glucagon has been reported to
be useful.
4. Bronchospasm: isoprenaline hydrochloride should be used. Additional therapy with
aminophylline may be considered.
5. Acute cardiac failure: conventional therapy with digitalis, diuretics, and oxygen should be
instituted immediately. In refractory cases, the use of intravenous aminophylline is
suggested. This may be followed, if necessary, by glucagon, which has been reported useful.
6. Heart block (second- or third-degree): isoprenaline hydrochloride or a pacemaker should
be used.

Timolol maleate is a non-selective beta-adrenergic receptor blocking agent that does not
have significant intrinsic sympathomimetic, direct myocardial depressant, or local
anaesthetic activity. Timolol maleate combines reversibly with the beta-adrenergic receptor,
and this inhibits the usual biologic response that would occur with stimulation of that
receptor. This specific competitive antagonism blocks stimulation of the beta-adrenergic
stimulating (agonist) activity, whether these originate from an endogenous or exogenous
source. Reversal of this blockade can be accomplished by increasing the concentration of the
agonist which will restore the usual biological response.
Unlike miotics, 'Optimol' reduces IOP with little or no effect on accommodation or pupil
size. In patients with cataracts, the inability to see around lenticular opacities when the pupil
is constricted is avoided. When changing patients from miotics to 'Optimol' a refraction
might be necessary when the effects of the miotic have passed.
Diminished response after prolonged therapy with 'Optimol' has been reported in some
patients.

The onset of reduction in intra-ocular pressure can be detected within one-half hour after a
single dose. The maximum effect occurs in one or two hours; significant lowering of IOP can be maintained for as long as 24 hours with a single dose.

No adverse ocular effects were observed in rabbits and dogs administered 'Optimol' topically
in studies lasting one and two years, respectively. The oral LD50 of the drug is 1,190 and 900
mg/kg in female mice and female rats, respectively.
Carcinogenesis, mutagenesis, impairment of fertility
In a two-year oral study of timolol maleate in rats there was a statistically significant
(p≤0.05) increase in the incidence of adrenal phaeochromocytomas in male rats
administered 300 mg/kg/day (300 times the maximum recommended human oral dose).
Similar differences were not observed in rats administered oral doses equivalent to 25 or 100
times the maximum recommended human oral dose.
In a lifetime oral study in mice, there were statistically significant (p≤0.05) increases in the
incidence of benign and malignant pulmonary tumours, benign uterine polyps and mammary
adenocarcinoma in female mice at 500 mg/kg/day (500 times the maximum recommended
human dose), but not at 5 or 50 mg/kg/day. In a subsequent study in female mice, in which
post-mortem examinations were limited to uterus and lungs, a statistically significant
increase in the incidence of pulmonary tumours was again observed at 500 mg/kg/day.
The increased occurrence of mammary adenocarcinoma was associated with elevations in
serum prolactin which occurred in female mice administered timolol at 500 mg/kg/day, but
not at doses of 5 or 50 mg/kg/day. An increased incidence of mammary adenocarcinomas in
rodents has been associated with administration of several other therapeutic agents which
elevate serum prolactin, but no correlation between serum prolactin levels and mammary
tumours has been established in man. Furthermore, in adult human female subjects who
received oral dosages of up to 60 mg of timolol maleate, the maximum recommended
human oral dosage, there were no clinically meaningful changes in serum prolactin.
Timolol maleate was devoid of mutagenic potential when evaluated in vivo (mouse) in the
micronucleus test and cytogenetic assay (doses up to 800 mg/kg) and in vitro in a neoplastic
cell transformation assay (up to 100 mcg/ml). In Ames tests the highest concentrations of
timolol employed, 5,000 or 10,000 mcg/plate, were associated with statistically significant
(p≤0.05) elevations of revertants observed with tester strain TA100 (in seven replicate
assays) but not in the remaining three strains. In the assays with tester strain TA100, no
consistent dose-response relationship was observed, nor did the ratio of test to control
revertants reach 2. A ratio of 2 is usually considered the criterion for a positive Ames test.

Sodium phosphate monobasic monohydrate
Sodium phosphate dibasic anhydrous
Sodium hydroxide
Benzalkonium chloride
Water for injections

None known.

Do not store above 30°C

Immediate container: LDPE (Low-Density Polyethylene) bottle 24-25 mm dia; white
(around 1% TiO2), round shape with rounded shoulder; indented ring
for tamper evident cap locking mechanism.
Cap: HDPE (High-Density Polyethylene) white (around 1% TiO2), round
shape with locking ring.
Nozzle: LDPE (Low-Density Polyethylene) Nozzle White (around 1.6%
TiO2).
Outer carton: 280g/m2 grammage paper, dimension 29 mm x 29.5 mm x 73 mm,
printing as per drawing.

Label: 20 x 73 mm, self adhesive
Insert/leaflet: 50-60 g/m2 paper, dimension 140 x 120 mm, both sides printed.

Patients should be instructed to avoid allowing the tip of the dispensing container to contact
the eye or surrounding structures.
Patients should also be instructed that ocular solutions, if handled improperly, can become
contaminated by common bacteria known to cause ocular infections. Serious damage to the
eye and subsequent loss of vision may result from using contaminated solutions.