Instructions Duotrav eye drops dropper bottle 2.5 ml
Composition
active ingredients: travoprost, timolol;
1 ml of solution contains travoprost 40 mcg, timolol 5 mg (as timolol maleate);
excipients: polyquad, propylene glycol, mannitol (E 421), boric acid, sodium chloride, polyethoxylated hydrogenated castor oil 40 (HCO-40), sodium hydroxide and/or hydrochloric acid (for pH adjustment), purified water.
Dosage form
Eye drops.
Main physicochemical properties: transparent, colorless to light yellow solution.
Pharmacotherapeutic group
Antiglaucoma drugs and miotics.
ATX code S01E D51.
Pharmacological properties
Pharmacodynamics. Duotrav® contains two active ingredients: travoprost and timolol maleate. These two substances reduce intraocular pressure due to a complementary mechanism of action and a combined effect that results in an additional reduction in intraocular pressure (IOP) compared to the effect achieved when using either of these components as monotherapy.
Travoprost, a prostaglandin F2a analogue, is a full agonist with high selectivity and high affinity for prostaglandin FP receptors, and reduces intraocular pressure by increasing the outflow of aqueous humor through the trabecular meshwork and uveoscleral pathways. The reduction in intraocular pressure in humans begins 2 hours after administration, and the maximum effect is achieved after 12 hours. Significant reductions in IOP are maintained for 24 hours after a single dose.
Timolol is a non-selective beta-adrenergic receptor blocker that has no significant sympathomimetic and local anesthetic (membrane stabilizing) activity, as well as no direct myocardial depressant effect. Tonographic and fluorometric studies have confirmed that its main action in humans is associated with a decrease in the formation of intraocular fluid and a slight increase in its outflow.
Secondary pharmacology
Travoprost significantly increased optic disc blood flow in rabbits 7 days after topical ocular administration (1.4 mcg once daily).
Clinical pharmacology
In a 12-month controlled clinical trial in patients with open-angle glaucoma or ocular hypertension and a mean IOP of 25 to 27 mmHg, the mean IOP reduction with Duotrav® administered once daily in the morning was 8 to 10 mmHg. During the study, it was demonstrated that the IOP reduction with the combination of latanoprost 50 μg/ml + timolol 5 mg/ml was not superior to that of Duotrav®.
In a three-month controlled clinical trial in patients with open-angle glaucoma or ocular hypertension and a mean IOP of 27 to 30 mmHg, the mean IOP reduction with Duotrav® administered once in the morning was 9 to 12 mmHg, which was 2 mmHg greater than that of travoprost 40 mcg/ml administered once in the evening and 2 to 3 mmHg greater than that of timolol 5 mg/ml administered twice daily. A statistically significant reduction in mean morning IOP (8 am, i.e. 24 hours after the last dose of Duotrav®) was observed during the study compared to travoprost.
In two three-month controlled clinical trials in patients with open-angle glaucoma or ocular hypertension and mean IOP of 23 to 26 mm Hg, the mean IOP reduction with Duotrav® administered once in the morning was 7 to 9 mm Hg. The mean IOP reduction was not insignificant, although quantitatively lower than in those receiving concomitant therapy with travoprost 40 mcg/ml once in the evening and timolol 5 mg/ml once in the morning.
In a six-week controlled clinical study in patients with open-angle glaucoma or ocular hypertension and a mean IOP of 24 to 26 mm Hg, the mean IOP reduction with Duotrav® with polyquaternium-1 as a preservative once daily in the morning was 8 mm Hg and was similar to that with Duotrav® with benzalkonium chloride as a preservative.
Inclusion criteria were the same for all studies, except for the IOP entry criterion and response to prior IOP-lowering therapy. Both drug-naïve and treatment-experienced patients participated in the clinical development of Duotrav®. Insufficient response to monotherapy was not an inclusion criterion.
The data suggest that evening dosing may have some benefit in reducing IOP. Recommendations for morning dosing rather than evening dosing should take into account patient convenience and compliance.
Preclinical safety data
Duotrav® with the preservative polyquaternium-1 resulted in minimal ocular surface toxicity in human corneal cell cultures and after topical application to the eye of rabbits compared to Duotrav® with benzalkonium chloride as a preservative.
Travoprost
Topical administration of travoprost at concentrations of 0.012% and higher to the right eye of monkeys twice daily for one year did not cause systemic toxicity.
Reproductive toxicity studies were conducted in rats, mice and rabbits using systemic administration. The findings were associated with FP receptor agonist activity in the uterus, which was manifested by early embryonic lethality, impaired fetal implantation, and fetal toxicity. In pregnant rats, systemic administration of travoprost during the period of organogenesis at doses 200 times the therapeutic dose resulted in an increased incidence of malformations. Low levels of radioactivity were measured in amniotic fluid and fetal tissues of pregnant rats administered 3H-travoprost. Reproductive and developmental studies have shown significant effects on fetal death, with a high rate of such cases in female rats and mice (180 pg/ml and 30 pg/ml in plasma, respectively) at doses 1.2-6 times the therapeutic dose (greater than 25 pg/ml).
Timolol
Preclinical data indicate that there is no risk to humans from the use of timolol, as evidenced by safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential. Studies of the toxic effects of timolol on reproductive function have shown delayed bone formation in rats in the absence of adverse effects on postnatal development (7000 times the clinical dose) and increased fetal resorption in rabbits (14000 times the clinical dose).
Pharmacokinetics.
Absorption
Travoprost and timolol are absorbed through the cornea. Travoprost is a prodrug that undergoes rapid ester hydrolysis in the cornea to the active free acid. After a single administration of Duotrav® (preserved with polyquaternium-1) to healthy volunteers (N = 22) for 5 days, the free acid was not quantifiable in plasma samples in the majority of subjects (94.4%) and was generally not detectable 1 hour after administration. When measured (> 0.01 ng/mL, limit of quantification), the concentration ranged from 0.01 to 0.03 ng/mL. The mean timolol Cmax after a single administration of Duotrav® was 1.34 ng/mL and Tmax was approximately 0.69 hours.
Distribution
Travoprost free acid can be quantified in the intraocular fluid within the first 5 hours in animals and in human plasma only within the first hour after Duotrav® ocular administration. Timolol can be detected in the intraocular fluid and human plasma 12 hours after Duotrav® ocular administration.
Metabolism
Metabolism is the major route of elimination for both travoprost and the active free acid. The systemic metabolic pathways parallel those of endogenous prostaglandin F2a, which are characterized by reduction of the 13–14 double bond, oxidation of the 15-hydroxyl group, and b-oxidative cleavage of the upper side chain.
Timolol is metabolized by two pathways. The first pathway involves the formation of an ethanolamine side chain on the thiodiazole ring, and the second involves the formation of an ethanol side chain on the morpholino nitrogen and another similar side chain with a carbonyl group adjacent to the nitrogen. The plasma half-life of timolol is 4 hours after instillation of Duotrav® into the eye.
Breeding
Travoprost free acid and its metabolites are excreted primarily by the kidneys. Less than 2% of an ophthalmic dose of travoprost free acid is recovered in the urine after ocular administration. Timolol and its metabolites are excreted primarily by the kidneys. Approximately 20% of a timolol dose is excreted unchanged in the urine, with the remainder also excreted in the urine as metabolites.
Indication
Duotrav® is indicated for the reduction of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who are inadequately responsive to topical beta-blockers or prostaglandin analogues.
Contraindication
Hypersensitivity to the active substances or other components of the drug.
Hypersensitivity to other beta-blockers.
Conditions accompanied by airway hyperresponsiveness, including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease.
Sinus bradycardia, sick sinus syndrome, including sinoatrial block, atrioventricular block of the 2nd–3rd degree, not controlled by a pacemaker.
Severe heart failure, cardiogenic shock.
Severe allergic rhinitis and corneal dystrophy.
Interaction with other medicinal products and other types of interactions
There is a possibility of additive effects leading to hypotension and/or marked bradycardia if eye drops containing a beta-blocker solution are used concomitantly with oral calcium channel blockers, beta-blockers, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, guanethidine. Hypertensive symptoms may be exacerbated by abrupt withdrawal of clonidine while taking beta-blockers.
Increased systemic effects of beta-blockers (including decreased heart rate, depression) have been reported with concomitant use of CYP2D6 inhibitors (such as quinidine, fluoxetine, paroxetine) and timolol.
Mydriasis has been reported rarely as a result of concomitant use of beta-blocker eye drops and adrenaline (epinephrine).
Beta-blockers may enhance the hypoglycaemic effect of antidiabetic medicinal products. Beta-blockers may mask the symptoms of hypoglycaemia (see section 4.4).
Application features
Systemic effects
Like other topical ophthalmic preparations, travoprost and timolol are absorbed systemically. Due to the presence of the beta-adrenergic active ingredient, timolol, the same cardiovascular, pulmonary and other adverse reactions as with systemic beta-adrenergic receptor blockers may occur. The incidence of systemic adverse reactions with topical ophthalmic use is lower than with systemic use. For reduced systemic absorption, see section 4.2.
Cardiac disorders
Beta-blocker treatment should be critically evaluated in patients with arterial hypotension and cardiovascular diseases (such as ischemic heart disease, Prinzmetal's angina and heart failure), and if necessary, treatment with other drugs should be considered.
Patients with cardiovascular diseases should be closely monitored to ensure that no worsening of symptoms of these diseases and adverse reactions are missed.
Given the negative effect on impulse conduction time, beta-blockers should be prescribed with caution only to patients with first-degree heart block.
Vascular disorders
Patients with severe peripheral circulatory disorders/diseases (such as severe Raynaud's disease or Raynaud's syndrome) should be treated with caution.
Respiratory dysfunction
Respiratory reactions, including fatal bronchospasm, have been reported in patients with asthma following the use of some topical ophthalmic beta-adrenergic receptor blockers.
Duotrav® should be used with caution in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only when the expected benefit outweighs the potential risk.
Hypoglycemia/diabetes
Beta-adrenergic receptor blockers should be used with caution in patients prone to spontaneous hypoglycemia or in patients with decompensated diabetes, since beta-adrenergic receptor blockers may mask the symptoms of acute hypoglycemia.
Muscle weakness
There have been reports of increased muscle weakness associated with myasthenic symptoms (such as diplopia, ptosis and general weakness) occurring with the use of beta-adrenergic receptor blockers.
Corneal diseases
Topical ophthalmic use of beta-blockers may cause dry eyes. The drug should be used with caution in patients with corneal diseases.
Detachment of the choroid of the eye
Choroid detachment has been reported with treatment aimed at reducing aqueous humor secretion (e.g., timolol, acetazolamide) following trabeculotomy.
Other beta-adrenergic receptor blockers
The effect on intraocular pressure or other known effects of systemic beta-blockers may be potentiated if timolol is administered to patients already receiving systemic beta-blockers. The response of such patients should be closely monitored.
The simultaneous use of two topical beta-blockers is not recommended (see section "Interaction with other medicinal products and other types of interactions").
Surgical anesthesia
When applied topically to the eye, beta-adrenergic receptor blockers may block the systemic beta-agonist effects of, for example, adrenaline. If the patient is prescribed timolol, the anaesthetist should be informed of this.
Hyperthyroidism
Beta-blockers can mask the symptoms of hyperthyroidism.
Skin contact
Prostaglandins and their analogues are biologically active substances that can be absorbed through the skin. Therefore, pregnant women or women who intend to become pregnant should take appropriate precautions to prevent skin contact with the product. In the event of accidental skin contact with a significant amount of the contents of the vial, the affected area should be thoroughly cleaned immediately.
When using beta-adrenergic receptor blockers, patients with atopic diseases or a history of severe anaphylactic reactions to various allergens may be more sensitive to repeated exposure to such allergens and may not respond to usual doses of adrenaline in the treatment of anaphylactic reactions.
Concomitant therapy
Timolol may interact with other medicines (see section “Interaction with other medicines and other types of interactions”).
Simultaneous topical use of two prostaglandins is not recommended.
Ophthalmological effects
Travoprost may gradually change eye colour by increasing the number of melanosomes (pigment granules) in melanocytes. Before starting treatment, patients should be informed of the possibility of irreversible changes in eye colour. Treatment of one eye may result in irreversible heterochromia. The long-term effects and consequences of the effects on melanocytes are currently unknown. The change in iris colour occurs slowly and may not be noticeable for months or years. Changes in eye colour have been observed first in patients with mixed iris colours, such as blue-brown, grey-brown, yellow-brown and green-brown; however, this phenomenon has also been observed in patients with brown eyes. Typically, the brown pigmentation around the pupil spread concentrically towards the periphery of the iris of the affected eye, but the whole iris or part of it may become more intensely brown. After stopping treatment, no further increase in brown pigment in the iris has been observed.
Darkening of the eyelid skin and/or periorbital area has been reported in controlled clinical trials with travoprost.
When using prostaglandin analogues, changes in the periorbital area and eyelid skin, including deepening of the eyelid sulcus, have been observed.
Travoprost may gradually change the structure of the eyelashes in the eye in which the drug is used; such changes were observed in half of the patients in clinical trials and included an increase in the length, thickness and pigmentation and/or number of eyelashes. The mechanism of the change in the structure of the eyelashes and the long-term consequences of this effect are still unknown.
A study in monkeys has shown that travoprost can slightly increase the palpebral fissure. However, this effect was not observed in clinical studies and is considered species-specific.
There is no experience with Duotrav® in inflammatory eye diseases, neovascular glaucoma, narrow-angle glaucoma, angle-closure or congenital glaucoma, and only limited experience with exophthalmos associated with thyroid disease, open-angle glaucoma in patients with pseudophakia, and pigmentary or pseudoexfoliative glaucoma.
Macular edema has been reported during treatment with prostaglandin F2α analogues.
Duotrav® is recommended to be prescribed with caution to patients with aphakia, pseudophakia, and with ruptured posterior lens capsule and anterior chamber lenses or to patients with known risk factors for the development of cystoid macular edema.
Duotrav® should be administered with caution to patients with active ocular infections and known risk factors for iritis/uveitis.
Excipients
Duotrav® contains propylene glycol, which may cause skin irritation.
Duotrav® contains polyethoxylated hydrogenated castor oil 40, which may cause skin reactions.
Patients should be informed that before using Duotrav®, contact lenses should be removed and that they should wait 15 minutes after instillation of the drug before reinserting contact lenses (see section “Method of administration and dosage”).
Use during pregnancy or breastfeeding
Women of reproductive age/contraception
Duotrav® should not be used in women of reproductive age who are not using adequate contraception (see section “Pharmacological properties”).
Pregnancy
Travoprost has harmful pharmacological effects on pregnant women and/or the fetus/newborn.
There are no adequate data from the use of Duotrav® or its individual components in pregnant women. Timolol should not be used during pregnancy unless clearly necessary. Epidemiological studies have not shown any developmental abnormalities, but have shown a risk of intrauterine growth retardation with oral beta-blockers. In addition, symptoms of beta-blockade (such as bradycardia, hypotension, respiratory depression and hypoglycemia) have been observed in neonates after administration of beta-blockers to pregnant women during the antenatal period. If Duotrav® is administered before delivery, neonates should be closely monitored during the first days of life.
Duotrav® should not be used during pregnancy unless clearly necessary. Regarding reduced systemic absorption, see section “Method of administration and dosage”.
It is not known whether travoprost is excreted in human milk when administered as eye drops. Animal studies have shown that travoprost and its metabolites are able to pass into human milk. Timolol passes into human milk and may cause serious adverse effects in the infant. However, given the dose of timolol in the eye drops, it is unlikely that sufficient timolol will be present in human milk to cause beta-blockade. For reduced systemic absorption, see Dosage and Administration.
The use of Duotrav® is not recommended for women during breastfeeding.
Reproductive function
There are no data on the effect of Duotrav® on human reproductive function. Animal studies have shown that travoprost and timolol at a dose 75 times the maximum recommended human ocular dose did not have a harmful effect on reproductive function.
Ability to influence reaction speed when driving vehicles or other mechanisms
Duotrav® has a minor influence on the ability to drive and use machines.
As with other eye drops, temporary blurred vision or other visual disturbances may occur. If blurred vision occurs during instillation, the patient should wait until the vision clears before driving or operating machinery.
Duotrav® may also cause hallucinations, dizziness, nervousness and/or fatigue (see section "Adverse reactions"), which may affect the ability to drive and use machines. It is recommended not to drive or use machines if these symptoms occur.
Method of administration and doses
Use in adults, including elderly patients.
The dose is 1 drop of Duotrav® in the conjunctival sac of the affected eye(s) once daily, in the morning or evening. The drug should be used at the same time each day.
If a dose is missed, treatment should be continued with the next dose according to the schedule. The dose should not exceed 1 drop per day in the affected eye(s).
Special patient groups
Use in liver and kidney dysfunction
No studies have been conducted on the use of Duotrav® or timolol 5 mg/ml eye drops in patients with impaired liver or kidney function.
Studies of travoprost in patients with mild to severe hepatic impairment and mild to severe renal impairment (creatinine clearance less than 14 ml/min) have shown that no dose adjustment is necessary in these patients. It is unlikely that Duotrav® will require dose adjustment in patients with hepatic or renal impairment (see section 5.1).
Children
The safety and efficacy of Duotrav® in children and adolescents (under 18 years of age) have not been established. Data are not available.
Method of application.
For ophthalmic use.
Remove the top protective packaging immediately before first use. To prevent contamination of the dropper tip and solution, care should be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip.
Systemic absorption will be reduced by applying pressure to the nasolacrimal orifice or gently closing the eyelids for 2 minutes. This will reduce systemic side effects and increase local activity (see section "Special instructions").
If more than one ophthalmic agent is applied topically, the interval between their applications should be at least 5 minutes (see section “Interaction with other medicinal products and other types of interactions”).
If one ophthalmic antiglaucoma drug is replaced with Duotrav®, the use of the other drug is discontinued and Duotrav® is started the next day.
Patients should be informed that contact lenses should be removed before using Duotrav® and that they should wait 15 minutes after instillation before reinserting contact lenses (see section “Special instructions”).
Children.
The safety and efficacy of Duotrav® for children and adolescents (under 18 years of age) have not been established, therefore the drug is not used in pediatric practice.
Overdose
Local overdose is unlikely to cause or be associated with toxic effects. Accidental ingestion of the contents of the vial (depending on the amount) may cause systemic symptoms of beta-blocker overdose: cardiac arrhythmias (e.g. bradycardia), hypotension, bronchospasm and heart failure.
In case of overdose with Duotrav®, treatment should be symptomatic and supportive. Timolol is not removed from the body by dialysis.
Side effects
Adverse reactions were assessed according to the classification of organs and systems, as well as by frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), rare (< 1/10,000) or frequency unknown (it is not possible to estimate their frequency from the available data). Adverse reactions are presented in order of decreasing seriousness.
Table 1
| Organ systems | Frequency | Adverse reactions |
| Immune system disorders | Infrequent | Hypersensitivity |
| Mental disorders | Single | Nervousness |
| Frequency unknown | Depression, hallucinations* |
| Nervous system disorders | Infrequent | Dizziness, headache |
| Frequency unknown | Stroke, transient loss of consciousness, paresthesia |
| Ophthalmological disorders | Very common | Eye hyperemia |
Frequent | Punctal keratitis, eye pain, visual disturbance, vision blurred, dry eye, eye itching, eye discomfort, eye irritation |
Infrequent | Keratitis, iritis, conjunctivitis, anterior chamber inflammation, blepharitis, photophobia, decreased visual acuity, asthenopia, eye swelling, increased lacrimation, eyelid erythema, increased eyelash growth, increased eye sensitivity, conjunctival edema, eyelid edema |
Single | Corneal erosion, meibomianitis, conjunctival hemorrhages, eyelid margin scaling, trichiasis, distichiasis |
| Frequency unknown | Macular edema, eyelid ptosis, deepening of the palpebral sulcus, iris hyperpigmentation, corneal disorders |
| Cardiological disorders | Infrequent | Bradycardia |
| Single | Arrhythmia, irregular heart rhythm |
| Frequency unknown | Heart failure, tachycardia, chest pain, palpitations |
| Vascular disorders | Infrequent | Increased blood pressure, decreased blood pressure |
| Frequency unknown | Peripheral edema |
| Respiratory, thoracic and mediastinal disorders | Infrequent | Dyspnea, excessive secretion of nasopharyngeal mucus |
Single | Dysphonia, bronchospasm, cough, throat irritation, sore throat, nasal congestion |
| Frequency unknown | Asthma |
| Gastrointestinal disorders | Frequency unknown | Change in taste sensations |
| Liver and biliary tract disorders | Single | Alanine aminotransferase increased, aspartate aminotransferase increased |
| Skin and subcutaneous tissue disorders | Infrequent | Contact dermatitis, hypertrichosis, skin hyperpigmentation (periorbital area) |
Single | Hives, skin discoloration, baldness |
| Frequency unknown | Rash |
| Musculoskeletal and connective tissue disorders | Single | Pain in the extremities |
| Renal and urinary disorders | Single | Chromaturia |
| General disorders and administration site conditions | Single | Thirst, fatigue |
* adverse reactions observed with the use of timolol.
Additional side effects that have been observed with the use of one of the active ingredients and may potentially occur with the use of Duotrav®:
Travoprost
Table 2
| Organ systems | Terms according to MedDRA classification |
| Immune system disorders | Seasonal allergies |
| Mental disorders | Anxiety, insomnia |
| Ophthalmological disorders | Uveitis, conjunctival follicle, eye discharge, periorbital edema, eyelid pruritus, ectropion, cataract, iridocyclitis, ophthalmic herpes, eye inflammation, photopsia, eyelid eczema, halo around light source, ocular hypoaesthesia, anterior chamber pigmentation, mydriasis, eyelash hyperpigmentation, eyelash thickening, visual field defect |
| Hearing and labyrinth disorders | Dizziness, tinnitus |
| Vascular disorders | Decreased diastolic blood pressure, increased systolic blood pressure |
| Respiratory, thoracic and mediastinal disorders | Asthma exacerbation, allergic rhinitis, nosebleed, respiratory tract disorder, nasal congestion, nasal dryness |
| Digestive tract disorders | Reactivation of peptic ulcer, gastrointestinal disorders, diarrhea, constipation, dry mouth, abdominal pain, nausea, vomiting |
| Skin and subcutaneous tissue disorders | Skin peeling, abnormal hair structure change, allergic dermatitis, hair color change, madarosis, pruritus, abnormal hair growth, erythema |
Musculoskeletal, connective tissue, bone disorders | Musculoskeletal pain, arthralgia | | Renal and urinary disorders | Dysuria, urinary incontinence |
| General disorders and administration site conditions | Asthenia |
| Research | Increased prostate-specific antigen levels |
Timolol
Like other topical ophthalmic drugs, timolol is absorbed into the systemic circulation. This may lead to side effects similar to those commonly seen with systemic beta-blockers. The additional side effects listed include reactions that have been observed with topical ophthalmic beta-blockers. The incidence of side effects with topical ophthalmic use is lower than with systemic use. For reduced systemic absorption, see section 4.2.
Table 3
| Organ systems | MedDRA terms |
| Immune system disorders | Systemic allergic reactions, including angioedema, urticaria, local and generalized rash, pruritus, anaphylaxis |
| Metabolic and digestive system disorders | Hypoglycemia |
| Mental disorders | Hallucinations, insomnia, nightmares, memory loss |
| Nervous system disorders | Cerebral vascular ischemia, increased signs and symptoms of myasthenia gravis |
| Ophthalmological disorders | Signs and symptoms of eye irritation (e.g. burning, stinging, itching, tearing, redness), choroid detachment after trabeculotomy (see section "Special instructions"), decreased corneal sensitivity, diplopia |
| Cardiological disorders | Edema, congestive heart failure, atrioventricular block, cardiac arrest |
| Vascular disorders | Raynaud's phenomenon, a feeling of coldness in the extremities |
| Gastrointestinal disorders | Nausea, dyspepsia, diarrhea, dry mouth, abdominal pain, vomiting |
| Skin and subcutaneous tissue disorders | Psoriatic rash or exacerbation of psoriasis |
| Musculoskeletal and connective tissue disorders | Myalgia |
| Reproductive system and mammary gland disorders | Sexual dysfunction, decreased libido |
| General disorders and administration site conditions | Asthenia |
Reporting potential adverse reactions.
It is very important to report suspected adverse reactions to a registered medicinal product. This allows us to continue to monitor the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report potential adverse reactions in accordance with applicable legislation.
Expiration date
2 years. Do not use for more than 4 weeks after first opening the bottle.
Storage conditions
Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
2.5 ml in a dropper bottle; 1 dropper bottle in an intermediate packaging, which is placed in a cardboard box.
Vacation category
According to the recipe.
Producer
Alcon Couvreur/Alcon Couvreur.
Location of the manufacturer and address of its place of business.
Rijksweg 14, Puurs-Sint-Amands, 2870, Belgium.
