Page 1 - GLAUCOME MLS A4 BA

1. NAME OF THE MEDICINAL PRODUCT: TIMOGEL® 1 mg/g, eye gel in single-dose container. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION: 1 g of gel contains 1 mg of timolol as timolol maleate.For the full list of excipients, see section 6.1.3. PHARMACEUTICAL
FORM: Eye gel in single-dose container.Opalescent, colourless to slightly yellow gel.4. CLINICAL PARTICULARS: 4.1 Therapeutic indications: Reduction of the elevated intraocular pressure in patients with: - ocular hypertension, - chronic open angle glaucoma. 4.2 Posology
and method of administration: Ocular use. Adults: The recommended dosage regimen is 1 drop of TIMOGEL® 1 mg/g in the affected eye (or eyes), once a day, in the morning. Elderly: There has been wide experience with the use of timolol eye drops in elderly patients.
The dosage recommendations given above reflect the clinical data derived from this experience. Children and adolescents: There is no experience in children and adolescents. This eye gel is therefore not recommended in such patients. If the ophthalmologist considers it
necessary, TIMOGEL® 1 mg/g may be combined with one or more other anti-glaucoma treatments (local and/or systemic route of administration). However, the combination of two beta-blocker eye drops is not recommended (see section 4.4.). The other eye drops should
be administered at least 15 minutes before TIMOGEL® 1 mg/g. The eye gel should be the last medication instilled. Nonetheless, response to TIMOGEL® 1 mg/g may take several weeks to stabilise intraocular pressure, therefore the monitoring of the treatment should include
intraocular pressure assessment after a treatment period of approximately four weeks. Method of administration: Timolol eye gel should be instilled into the conjunctival sac. A single-dose contains enough gel to treat both eyes. For single use only. Patients should be
instructed: - to avoid contact between the dropper tip and the eye or eyelids, - to use the eye gel immediately after first opening the single-dose container and to discard the single-dose after use. When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the
systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity. Replacement of a previous treatment: When TIMOGEL® 1 mg/g is used to replace another anti-glaucoma eye drops, this eye drops should be discontinued
after a full day of therapy, and TIMOGEL® 1 mg/g should be started the next day at the dosage of one drop in the affected eye (or eyes) once a day, in the morning. If TIMOGEL® 1mg/g is replacing a combination of anti-glaucoma treatments, only one drug should be
withdrawn at a time. If the anti-glaucoma drug being replaced is not a beta-blocker eye drops, it should be continued and one drop of TIMOGEL® 1 mg/g should be instilled in the affected eye (or eyes), once a day. The following day, stop taking the previous drug completely.
When TIMOGEL® 1 mg/g is used to replace miotic eye drops, testing of refraction may prove necessary when the effects of the miotics have disappeared. Medical prescription should be combined with the monitoring of intraocular pressure, particularly when the treatment
is initiated. 4.3 Contraindications: As with all products containing beta-receptor blocking agents, Timolol is contraindicated in patients with: - Hypersensitivity to the active substance (timolol maleate), or to any of the excipients listed in section 6.1, -Reactive airway disease
including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease, - Sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker. - Overt cardiac failure,
cardiogenic shock, - Untreated pheochromocytoma, - Corneal dystrophies. 4.4 Special warnings and precautions for use: Like other topically applied ophthalmic agents timolol maleate is absorbed systemically. Due to betaadrenergic component, timolol maleate, the same
types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. To reduce the systemic absorption,
see 4.2. As with any glaucoma treatment, regular examination of the intraocular pressure and cornea is recommended. If TIMOGEL® 1 mg/g is administered to reduce intraocular pressure in patients with closed-angle glaucoma, a miotic should be used in combination. In
such patients, the immediate objective of the treatment is to reopen the angle, which requires the use of a miotic agent in order to obtain pupil constriction, since timolol maleate has little or no effect on the pupil. Cardiac disorders: In patients with cardiovascular diseases
(e.g. coronary heart disease, Prinzmetal’s angina and cardiac failure) and hypotension therapy with beta-blockers should be critically assessed and the therapy with other active substances should be considered. Patients with cardiovascular diseases should be watched for
signs of deterioration of these diseases and of adverse reactions. Due to its negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block. The dosage should be reduced if the rate falls below 50-55 beats per
minute at rest, and if the patient presents bradycardia-related symptoms. Beta-blockers may increase the risk of rebound hypertension. Vascular disorders: Patients with severe peripheral circulatory disturbance/disorders (i.e. severe forms of Raynaud’s disease or Raynaud’s
syndrome) should be treated with caution. Treated pheochromocytoma: These patients should not receive β-blocking agents without concomitant α-adrenoceptor blocking therapy. Respiratory disorders: Respiratory reactions, including death due to bronchospasm in
patients with asthma have been reported following administration of some ophthalmic betablockers. TIMOGEL® should be used with caution, in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only if the potential benefit outweighs the
potential risk. Hypoglycaemia/diabetes: Beta-blockers should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia. Beta-blockers
may also mask the signs of hyperthyroidism. Metabolic disease: It should be used with caution in patients with metabolic acidosis. Corneal diseases: Ophthalmic β -blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution. Patients
wearing contact lenses: There is a risk of intolerance to contact lenses due to a beta-blocker induced reduction in lacrimal secretion. Timolol eye gel has not been studied in patients using contact lenses, and therefore the wearing of contact lenses should be avoided while
using of TIMOGEL®. Other beta-blocking agents: The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when timolol maleate is given to the patients already receiving a systemic beta-blocking agent. The response of these
patients should be closely observed. The use of two topical beta-adrenergic blocking agents is not recommended (see section 4.5). Anaphylactic reactions: While taking beta-blockers, patients with 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 and unresponsive to the usual dose of adrenaline used to treat anaphylactic reactions. Choroidal detachment: Choroidal detachment has been reported with administration of aqueous suppressant
therapy (e.g. timolol, acetazolamide) after filtration procedures. Psoriasis: Beta-blockers have been reported to aggravate psoriasis and its use in this condition therefore deserves careful consideration. Withdrawal of therapy: As with systemic beta-blockers, if discontinuation
of ophthalmic timolol is needed in patients with coronary heart disease, therapy should be withdrawn gradually. Elderly patients, impaired renal and/or hepatic function. When such agents are administered orally in such high-risk subjects, a dosage adjustment is often
necessary. Surgical anaesthesia: β-blocking ophthalmological preparations may block systemic. β-agonist effects e.g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving timolol maleate. Sportsmen: Sportsmen should be warned that this
drug contains an active substance, which may induce a positive analytical result in anti-doping controls. 4.5 Interaction with other medicinal products and other forms of interaction: No specific drug interaction studies have been performed with timolol maleate. Although
the quantity of beta-blockers, which passes into the systemic circulation is low after ocular instillation, the risk of drug interactions is still present. It is therefore advisable to keep in mind the interactions observed with beta-blockers given by general route. There is a potential
for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral calcium channel blockers, betaadrenergic blocking agents, antiarrhythmics (including amiodarone), digitalis glycosides,
parasympathomimetics, guanethidine. Potentiated systemic betablockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol. Mydriasis resulting from
concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally. Combination which are not recommended (see section 4.4): + Bepridil: Automatism disorders (excessive bradycardia, sinus arrest), sinoatrial and atrioventricular
conduction disorders and increased risk of ventricular rhythm disorders (torsades de pointes) as well as cardiac failure. This combination should only take place under close clinical and ECG monitoring, particularly in elderly subjects or in those beginning treatment. +
Diltiazem: Automatism disorders (excessive bradycardia, sinus arrest) sinoatrial and atrioventricular conduction disorders and cardiac failure. This combination should only take place under close clinical and ECG monitoring, particularly in elderly subjects or those starting
treatment. + Verapamil: Automatism disorders (excessive bradycardia, sinus arrest) sinoatrial and atrioventricular conduction disorders and cardiac failure. This combination should only take place under close clinical and ECG monitoring, particularly in elderly subjects or
those starting treatment. + Fingolimod: Potentiation of bradycardic effects can have fatal consequences. Beta-blockers are more at risk that they prevent adrenergic compensation mechanism. Continuous clinical and ECG monitoring during 24 hours after the first dose.
Combinations requiring precautions for use : + Amiodarone: Automatism and conduction disorders (suppression of compensatory sympathetic mechanisms). Clinical and ECG monitoring is recommended. + Class I antiarrhythmics (except lidocaine): Contractility,
automatism and conduction disorders (suppression of compensatory sympathetic mechanisms). Clinical and ECG monitoring is recommended. + Volatile halogenated anaesthetic agents: Reduction in compensatory cardiovascular mechanisms by beta-blockers. Beta-
adrenergic inhibition may be counteracted during surgery by beta-mimetics. As a general rule, do not discontinue beta-blocker therapy, and in any event, avoid a sudden discontinuation. The anaesthetist should be advised of this treatment. + Baclofen: Enhancement of
hypotension risk, notably orthostatic. Blood pressure monitoring and, if necessary, dosage adjustment of the antihypertensive. + Central anti-hypertensives: Significant increase in arterial pressure if treatment with a central anti-hypertensive is suddenly discontinued.
Avoid sudden withdrawal of treatment with a central anti-hypertensive. Clinical monitoring. + Insulin, oral hypoglycaemic agents ; Glinides ; Gliptines: All beta-blockers may mask certain symptoms of hypoglycaemia: palpitations and tachycardia. Warn the patient and,
particularly at the beginning of treatment, self-monitoring of glycaemia by the patient should be increased. + Lidocaine: With lidocaine used intravenously: increase in plasmatic concentrations of lidocaine with a possibility of adverse neurological and cardiac side effects
(reduction in hepatic clearance of lidocaine). Clinical and ECG monitoring and possibly testing of the plasmatic concentrations of lidocaine during the combined therapy and after the beta-blocker has been withdrawn. Adaptation if necessary of dosage regimen of lidocaine.
+ Drugs which may cause torsades de pointes: Enhanced risk of ventricular arrhythmia, particularly torsades de pointes. Clinical and ECG monitoring is recommended. + Propafenone: Contractility, automatism and conduction disorders (suppression of compensatory
sympathetic mechanisms). Clinical and ECG monitoring is recommended. Combinations to be taken into account: + Alpha-blockers intended for urological use; Anti-hypertensive alpha-blockers: Enhancement of hypotensive effect. Increased risk of orthostatic
hypotension. + Amifostine: Enhancement of hypotension risk, notably orthostatic. + Imipraminic antidepressants: Enhancement of hypotension risk, notably orthostatic. + Neuroleptic: Enhancement of hypotension risk, notably orthostatic. Vasodilatator effect and risk of
hypotension, notably orthostatique (additional effect). + Non-steroidal anti-inflammatory drugs: Reduction in the antihypertensive effect (inhibition of vasodilator prostaglandins by non-steroidal anti-inflammatory drugs and of water and salt retention by phenylbutazone).
+ Other bradycardial drugs: Risk of excessive bradycardia (additive effects). + Dihydropyridines: Hypotension, cardiac failure in patients with latent or uncontrolled cardiac insufficiency (additional negative inotropic effects). Moreover, the beta-blocker can minimise the
sympathetic reflex reaction, which comes into play in the event of excessive haemodynamic repercussion. + Dipyridamole: With the dipyridamole by intravenous route: enhancement of the anti-hypertensive effect. + Pilocarpine (for systemic use): Risk of excessive
bradycardia (additive bradycardial effects). + Nitro derivatives and related: Enhancement of hypotension risk, notably orthostatic. 4.6 Fertility, pregnancy and lactation: Pregnancy: There are no adequate data for the use of timolol maleate in pregnant women. Timolol
maleate should not be used during pregnancy unless clearly necessary. To reduce the systemic absorption, see 4.2. Epidemiological studies have not revealed malformative effects but show a risk for intra uterine growth retardation when beta-blockers are administered
by the oral route. In addition, signs and symptoms of betablockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If TIMOGEL® is administered until
delivery, the neonate should be carefully monitored during the first days of life. Breast-feeding: Beta-blockers are excreted in breast milk. However, at therapeutic doses of timolol maleate in eye drops it is not likely that sufficient amounts would be present in breast milk
to produce clinical symptoms of beta-blockade in the infant. To reduce the systemic absorption, see 4.2. Fertility: Timolol maleate has not been found to have any effect on fertility in animal studies (see section 5.3). 4.7 Effects on ability to drive and use machines: TIMOGEL®
has minor influence on the ability to drive and use machines. No studies on the effect of this medicinal product on the ability to drive have been conducted. While driving vehicles or operating different machines, it should be taken into account that occasionally visual
disturbances may occur including refractive changes, diplopia, ptosis, frequent episodes of mild and transient blurred vision and occasional episodes of dizziness or fatigue. 4.8 Undesirable effects: Like other topically applied ophthalmic drugs, timolol maleate is absorbed
into the systemic circulation. This may cause similar undesirable effects as seen with systemic betablocking agents. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. Listed adverse reactions include reactions seen
within the class of ophthalmic beta-blockers. Immune system disorders: Systemic lupus erythematosus, systemic allergic reactions including angioedema, urticaria, localized and generalized rash, pruritus, anaphylactic reaction. Metabolism and nutrition disorders:
Hypoglycaemia. Psychiatric disorder:Insomnia, depression, nightmares, memory loss, hallucination. Nervous system disorders:Syncope, cerebrovascular accident, cerebral ischemia, increases in signs and symptoms of myasthenia gravis, dizziness, paraesthesia, and
headache. Eye disorders: Signs and symptoms of ocular irritation (e.g. burning, stinging, itching, tearing, redness), blepharitis, conjunctival hyperaemia, conjunctivitis, keratitis, blurred vision and choroidal detachment following filtration surgery (see 4.4 Special warnings
and special precautions for use), decreased corneal sensitivity, dry eyes, corneal erosion ptosis, diplopia, refractive changes (due to withdrawal of miotic therapy in some cases). Cardiac disorders:Bradycardia, chest pain, palpitations, oedema, arrhythmia, congestive heart
failure, atrioventricular block, cardiac arrest, cardiac failure, claudication. Vascular disorders:Hypotension, Raynaud’s phenomenon, cold hands and feet. Respiratory, thoracic, and mediastinal disorders:Bronchospasm (predominantly in patients with pre-existing
bronchospastic disease), dyspnoea, cough. Gastrointestinal disorders:Dysgeusia, nausea, dyspepsia, diarrhoea, dry mouth, abdominal pain, vomiting. Skin and subcutaneous tissue disorders:Alopecia, psoriasiform rash or exacerbation of psoriasis, skin rash. Musculoskeletal
and connective tissue disorders:Myalgia. Reproductive system and breast disorders: Sexual dysfunction, decreased libido, impotence. General disorders and administration site conditions:Asthenia/fatigue. Investigations: Antinuclear antibodies positive. 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 listed in Appendix V. 4.9 Overdose: No data specific to this preparation are available. The most common side effects caused by beta-blocker overdosage are symptomatic bradycardia, hypotension, bronchospasm, and
acute cardiovascular insufficiency. If overdosage occurs, the following measures should be considered: 1. Administration of activated charcoal, if the preparation has been taken orally. Studies have shown that timolol maleate cannot be removed by haemodialysis. 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 should
be considered. 3. Hypotension: A sympathomimetic agent such as dopamine, dobutamine or noradrenaline should be given. In refractory cases, the use of glucagon has been useful. 4. Bronchospasm: Isoprenaline hydrochloride should be given. Concomitant 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 recommended. This may be followed, if necessary, by glucagon,
which has been found useful. Heart blocks: Isoprenaline hydrochloride or a pacemaker should be used. 5. PHARMACOLOGICAL PROPERTIES: 5.1 Pharmacodynamic properties: Pharmacotherapeutic group : ANTIGLAUCOMA PREPARATIONS AND MIOTICS; Beta-blocking
agents ATC code: S01ED01. General: Timolol can be characterised by three pharmacological properties: - non-cardioselective beta-blockade, - partial agonist potential [moderate intrinsic sympathomimetic activity (ISA)], - non-significant membrane stabilising effect (local
anaesthetic or quinidine-like). - Ocular: - timolol maleate eye gel reduces intra-ocular pressure, whether or not this is associated with glaucoma; - an effect is seen around 20 minutes following instillation, reaches a maximum in 1 to 2 hours and is still present after 24 hours;
- there is no effect on pupil diameter or visual acuity. 5.2 Pharmacokinetic properties: Timolol eye gel 1 mg/g is a preservative free formulation. Negligible systemic exposure has been observed in patients treated with Timolol eye gel 1 mg/g given once daily. Data from a
recent comparative pharmacokinetic study (LOQ = 0.146 ng/ml) have shown that the plasma level is generally below the LOQ. 5.3 Preclinical safety data: None of the mutagenesis studies carried out in vivo and in vitro on timolol have produced any evidence of mutagenic
potential. Cancerogenic potential in timolol has been shown in animals, at exposure levels much higher than those observed in clinical practice during treatment with TIMOGEL® 1 mg/g. Reprotoxicity studies have not shown any teratogenic effect in mice, rats and rabbits.
In rats, a delay in ossification was observed at levels of exposure much higher than those observed in clinical practice during treatment with TIMOGEL® 1 mg/g. No effects on fertility were observed in rats. In rabbits, a single or repeated instillation of TIMOGEL® 1mg/g for
28 days did not cause any local or systemic intolerance, nor local anaesthetic effect. 6. PHARMACEUTICAL PARTICULARS: 6.1 List of excipients: Sorbitol, Polyvinyl alcohol, Carbomer 974 P, Sodium acetate trihydrate, Lysine monohydrate, Water for injections. 6.2
Incompatibilities: Not applicable. 6 3 Shelf life: 30 months. After opening of the single-dose container: use immediately and discard the single-dose container after use. After opening of the sachet: use the single-dose containers within 1 month. 6.4 Special precautions
for storage: Keep the single-dose containers in the sachet and the outer carton in order to protect from light. 6.5 Nature and contents of container: 10 single-dose containers (PEBD) containing 0.4 g of gel are packed in sachet (paper/aluminium), box of 3 or 9 sachets. A
pack size contains 30 (3x10) or 90 (9x10) single-dose containers. Not all pack sizes may be marketed. 6.6 Special precautions for disposal: No special requirements. 7. MARKETING AUTHORISATION HOLDER: LABORATOIRES THEA - 12, RUE LOUIS BLERIOT - 63017
CLERMONT-FERRAND CEDEX 2 8. MARKETING AUTHORISATION NUMBER(S): FR/H/0288/001/MR. 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION: 03/01/2006. 10. DATE OF REVISION OF THE TEXT: 18/12/2019.
Elymbus® 0.1 mg/g eye gel in single-dose container
1. NAME OF THE MEDICINAL PRODUCT: Elymbus ® 0.1 mg/g eye gel in single-dose container 2. QUALITATIVE AND QUANTITATIVE COMPOSITION: One g of eye gel contains 0.1 mg bimatoprost. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM: Eye
gel. Colourless opalescent gel. pH: 6.9 – 7.9. Osmolality: 250 – 350 mosmol/kg. 4. CLINICAL PARTICULARS: 4.1 Therapeutic indications: Reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension in adults (as monotherapy or as
adjunctive therapy to beta-blockers). 4.2 Posology and method of administration: Posology: The recommended dose is one drop in the affected eye(s) once daily, administered in the evening. The dose should not exceed once daily, as more frequent administration may
lessen the intraocular pressure lowering effect. Special populations: Patients with hepatic impairment: Elymbus® has not been studied in patients with moderate to severe hepatic impairment and should therefore be used with caution in such patients. In patients with
a history of mild liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin at baseline, bimatoprost 0.3 mg/ml eye drops, solution (preserved formulation) had no adverse effect on liver function over 24 months. Patients
with renal impairment: Elymbus® has not been studied in patients with renal impairment and should therefore be used with caution in such patients. Paediatric population: The safety and efficacy of Elymbus® in children aged 0 to 18 years has not yet been established.
Method of administration: Ocular use. The use of bimatoprost in contact lens wearers has not been studied. Therefore, contact lenses should be removed before instillation of the eye gel and may be reinserted after 15 minutes. If more than one topical ophthalmic
medicinal product is being used, they should be administered at least 15 minutes before Elymbus® . Elymbus® should be instilled last. A single-dose container contains enough eye gel to treat both eyes. For single-use only. This medicinal product is a sterile eye gel that
does not contain a preservative. The eye gel from one individual single-dose container is to be used immediately after opening for administration to the affected eye(s). Since sterility cannot be maintained after the individual single-dose container is opened, any remaining
contents must be discarded immediately after administration. Patients should be instructed: - to avoid contact between the dropper tip and the eye or eyelids. - to use the eye gel immediately after first opening the single-dose container and to discard the single-dose
container after use. - to store the unopened single-dose containers in the sachet. 4.3 Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 4.4 Special warnings and precautions for use: Ocular: Before treatment is
initiated, patients should be informed of the possibility of prostaglandin analogue periorbitopathy (PAP) and increased iris pigmentation, since these have been observed during treatment with bimatoprost 0.1 mg/ml eye drops, solution (preserved formulation). Some of
these changes may be permanent, and may lead to impaired field of vision and differences in appearance between the eyes when only one eye is treated (see section 4.8). Cystoid macular oedema has been uncommonly reported (≥1/1,000 to <1/100) following treatment
with bimatoprost 0.3 mg/ml eye drops, solution (preserved formulation). Therefore, Elymbus® should be used with caution in patients with known risk factors for macular oedema (e.g. aphakic patients, pseudophakic patients with a torn posterior lens capsule). There
have been rare spontaneous reports of reactivation of previous corneal infiltrates or ocular infections with bimatoprost 0.3 mg/ml eye drops, solution (preserved formulation). Elymbus® should be used with caution in patients with a prior history of significant ocular viral
infections (e.g. herpes simplex) or uveitis/iritis. Elymbus® has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma. Skin: There is a potential for hair growth
to occur in areas where Elymbus® comes repeatedly in contact with the skin surface (see section 4.8). Thus, it is important to apply Elymbus® as instructed and avoid it running onto the cheek or other skin areas. Respiratory: Elymbus® has not been studied in patients with
compromised respiratory function. While there is limited information available on patients with a history of asthma or COPD, there have been reports of exacerbation of asthma, dyspnoea and COPD, as well as reports of asthma, in post marketing experience (see section
4.8). The frequency of these symptoms is not known. Patients with COPD, asthma or compromised respiratory function due to other conditions should be treated with caution. Cardiovascular: Elymbus® has not been studied in patients with heart block more severe than
first degree or uncontrolled congestive heart failure. There have been a limited number of spontaneous reports of bradycardia or hypotension with bimatoprost 0.3 mg/ml eye drops, solution (preserved formulation) (see section 4.8). Elymbus® should be used with caution
in patients predisposed to low heart rate or low blood pressure. Other Information: In studies of bimatoprost 0.3 mg/ml in patients with glaucoma or ocular hypertension, it has been shown that the more frequent exposure of the eye to more than one dose of bimatoprost
daily may decrease the IOP-lowering effect (see section 4.5). Patients using Elymbus® with other prostaglandin analogues should be monitored for changes to their intraocular pressure. 4.5 Interaction with other medicinal products and other forms of interaction: No
interaction studies have been performed. No interactions are anticipated in humans, since systemic concentrations of bimatoprost are extremely low (less than 0.2 ng/ml) following ocular dosing with bimatoprost 0.3 mg/ml eye drops, solution (preserved formulation).
Bimatoprost is biotransformed by any of multiple enzymes and pathways (see section 5.2), and no effects on hepatic drug metabolising enzymes were observed in preclinical studies. In clinical studies, bimatoprost 0.3 mg/ml eye drops, solution (preserved formulation) was
used concomitantly with a number of different ophthalmic beta-blocking agents without evidence of interactions. Concomitant use of bimatoprost and antiglaucomatous agents other than topical beta-blockers has not been evaluated during adjunctive glaucoma therapy.
There is a potential for the IOP-lowering effect of prostaglandin analogues (e.g. Elymbus® ) to be reduced in patients with glaucoma or ocular hypertension when used with other prostaglandin analogues (see section 4.4). 4.6 Fertility, pregnancy and lactation: Pregnancy:
There are no adequate data from the use of bimatoprost in pregnant women. Animal studies have shown reproductive toxicity at high maternotoxic doses (see section 5.3). Elymbus® should not be used during pregnancy unless clearly necessary. Breast-feeding: It is
unknown whether bimatoprost is excreted in human breast milk. Animal studies have shown excretion of bimatoprost in breast milk. A decision must be made whether to discontinue breast-feeding or to discontinue from Elymbus® therapy taking into account the benefit
of breast-feeding for the child and the benefit of therapy for the woman. Fertility: There are no data on the effects of bimatoprost on human fertility. 4.7 Effects on ability to drive and use machines: Elymbus® has minor influence on the ability to drive and use machines.
As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machines. 4.8 Undesirable effects: In a 3-month phase III clinical study comparing the efficacy and safety of preservative-free
Elymbus® versus preserved bimatoprost 0.1 mg/ml eye drops solution reference product, 236 patients were exposed to Elymbus® . The most frequently reported adverse reactions with Elymbus® were conjunctival hyperaemia (6.8%), eye irritation (5.1%), foreign body
sensation in eye (2.5%), dry eye (2.5%) and transient blurred vision (2.1%). Table 1 lists adverse reactions identified with Elymbus® in the phase III trial. Most were ocular, mild and none was serious. Adverse reactions associated with Elymbus® are listed by system organ
class and frequency. Frequency categories are defined as: 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 available data) adverse reactions are
presented according to System Organ Class in Table 1 in order of decreased seriousness within each frequency grouping.

Table 1.
System Organ Class Frequency Adverse reaction
Eye disorders common conjunctival hyperaemia, eye pain, eye irritation, noninfective conjunctivitis, foreign body sensation in eyes, dry eye, eye pruritus,
transient blurred vision*
uncommon punctate keratitis, eye paraesthesia, blepharitis, madarosis, growth of eyelashes, photophobia, lacrimation increased, eyelash darkening,
blepharal pigmentation, eyelid oedema, eyelid eczema
Nervous system disorders uncommon dizziness
* transient blurred vision after ocular administration of the eye gel (see section 4.7).