Oftimol®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OPHТIMOL® (OPHTIMOL)

Composition:

Active substance: timolol;

1 ml of the preparation contains 5 mg of timolol maleate calculated as 100 % timolol;

Excipients: benzalkonium chloride; sodium chloride; sodium dihydrogen phosphate dihydrate; disodium hydrogen phosphate dodecahydrate; water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear colorless liquid.

Pharmacotherapeutic group.

Medicinal products used in ophthalmology. Anti-glaucoma preparations and miotics. Beta-adrenoreceptor blockers.

ATC code S01ED01.

Pharmacological properties.

Pharmacodynamics.

Timolol is a non-selective (β1 and β2) beta-blocker that has no significant intrinsic sympathomimetic or membrane-stabilizing activity, nor direct suppressive effects on the myocardium.

Ophthalmic administration of timolol maleate effectively reduces both normal and elevated intraocular pressure. Based on fluorometric studies, timolol maleate decreases the production of aqueous humor without significantly affecting fluid outflow. The cellular mechanisms underlying the reduced aqueous humor production in the processes occurring within the ciliary body of the eye are not yet fully understood.

Unlike treatment with miotics, timolol reduces intraocular pressure without affecting accommodation, pupil size, or visual acuity; therefore, blurred or hazy vision and impaired vision in bright light do not occur. Furthermore, in patients with cataracts, visual disturbances associated with pupil constriction caused by lens opacity can be avoided.

Pharmacokinetics.

The effect of the drug begins 20 minutes after instillation. A reduction in intraocular pressure can typically be detected within 30 minutes after instillation. Maximum reduction is achieved within 1–2 hours. The reduction in intraocular pressure persists for 24 hours after a single dose.

Clinical characteristics.

Indications.

Ocular hypertension, chronic open-angle glaucoma, and certain cases of secondary glaucoma.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Conditions associated with hyperreactivity of the respiratory tract, including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease.

Sinus bradycardia, sick sinus syndrome, sinoatrial block, second- or third-degree atrioventricular block not controlled by a pacemaker, severe heart failure, or cardiogenic shock.

Interaction with other medicinal products and other forms of interactions.

Studies on the interaction of timolol with other medicinal products have not been conducted. Enhanced effects of systemic beta-blockers (e.g., reduced heart rate, depression) have been reported during concomitant treatment with CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) and timolol.

An additive effect leading to hypotension and/or marked bradycardia may occur when beta-blocker eye drops are used concomitantly with oral calcium channel blockers, beta-adrenoblockers, antiarrhythmic agents (including amiodarone), digitalis glycosides, parasympathomimetics, or guanethidine.

Rarely, mydriasis has been reported with concomitant use of beta-blocker eye drops and adrenaline (epinephrine).

If more than one ophthalmic medicinal product is to be administered locally, an interval of at least 5 minutes between instillations should be observed. Ophthalmic ointments should be applied last.

Special precautions for use.

For ophthalmic use only.

General

Timolol is systemically absorbed, as are other topically applied ophthalmic agents.

Due to the presence of a beta-adrenergic blocking component, timolol used in ophthalmology may cause adverse reactions affecting the cardiovascular, respiratory and other systems, similar to those observed with systemic beta-blockers. The frequency of systemic adverse reactions after topical ophthalmic administration is lower than with systemic administration. To minimize systemic absorption, see information provided in the section "Dosage and administration".

Cardiac disorders

In patients with cardiovascular disorders (e.g., ischemic heart disease, Prinzmetal's angina, heart failure) and arterial hypotension, treatment with beta-blockers should be carefully evaluated and therapy with agents having different active substances should be considered. Patients with cardiovascular disorders should be monitored for signs of worsening of their condition and possible occurrence of adverse reactions. Because of the negative effect on impulse conduction, beta-blockers should be administered with great caution to patients with first-degree heart block.

Vascular disorders

Treatment should be administered with caution to patients with severe disorders of peripheral circulation (e.g., severe form of Raynaud's disease or Raynaud's syndrome).

Respiratory disorders

Adverse reactions affecting the respiratory system, including fatal bronchospasm in patients with asthma, have been reported after use of some ophthalmic beta-blockers.

Oftimol® should be used with caution in patients with mild or moderate chronic obstructive pulmonary disease (COPD) and only if the potential benefit outweighs the potential risk.

Hypoglycemia/diabetes

Since beta-blockers may mask signs and symptoms of acute hypoglycemia, they should be administered with caution to patients prone to spontaneous hypoglycemia or with labile diabetes.

Hyperthyroidism

Beta-blockers may mask signs of hyperthyroidism.

Muscle weakness

Beta-adrenergic blockers have been reported to exacerbate muscle weakness associated with certain symptoms of myasthenia gravis (e.g., diplopia, ptosis, and generalized weakness).

Corneal disorders

Ophthalmic beta-blockers may cause dry eyes. Treatment should be administered with caution to patients with corneal disorders.

Other beta-blockers

The effect on intraocular pressure or known effects of systemic beta-blockers may be enhanced when timolol is administered to patients already receiving systemic beta-blockers. Such patients should be carefully monitored. Concomitant use of two topical beta-adrenergic blockers is not recommended (see "Interaction with other medicinal products and other forms of interaction").

Anaphylactic reactions

Patients with a history of atopy or severe anaphylactic reactions to various allergens may be more sensitive to re-exposure to such allergens while taking beta-blockers and may be unresponsive to usual doses of adrenaline used to treat anaphylactic reactions.

Choroidal detachment

Choroidal detachment has been reported with therapy that suppresses aqueous humor production (e.g., timolol, acetazolamide) following trabeculotomy.

Anesthesia during surgical procedures

Ophthalmic beta-blockers may block the systemic effects of beta-agonists, such as adrenaline. The anesthesiologist should be informed that the patient is receiving timolol.

Contact lenses

Benzalkonium chloride may cause irritation and is known to discolor soft contact lenses. Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses before instilling Oftimol® and to wait at least 15 minutes before reinserting them.

Use during pregnancy or breastfeeding.

Fertility

There are no data on the effect of Oftimol® on fertility.

Pregnancy

There are no adequate data on the use of Oftimol® in pregnant women.

Epidemiological studies have not shown a teratogenic effect, but have demonstrated a risk of intrauterine growth retardation with oral administration of beta-blockers. In addition, signs and symptoms of beta-blocker effects in newborns (e.g., bradycardia, hypotension, respiratory distress, and hypoglycemia) have been observed when beta-blockers were administered before delivery. Timolol should not be used during pregnancy except when clearly necessary. However, if Oftimol® is used before delivery, the newborn should be under close medical supervision during the first days of life. Information on reducing systemic absorption is provided in the section "Dosage and administration".

Breastfeeding

Beta-blockers pass into breast milk and may cause serious adverse effects in breastfed infants.

After careful assessment of the benefit-risk ratio, breastfeeding should be discontinued or treatment with Oftimol® should be stopped, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the woman.

Ability to affect reaction speed when driving or operating machinery.

Transient blurred vision or other visual disturbances, including refractive changes, diplopia, ptosis, frequent mild and transient episodes of blurred vision, and rarely dizziness or fatigue, may affect the ability to drive a vehicle or operate machinery.

If blurred vision occurs upon instillation, the patient should wait until vision clears before driving or operating machinery.

Method of Administration and Dosage

Warning! Do not tightly screw the bottle cap before initial use! Before first use, screw the cap on completely. In doing so, the spike located on the inner side of the cap will puncture the seal. Immediately before administration, hold the bottle in the palm of the hand to warm it to body temperature. Unscrew and remove the cap, then instill the solution into the eye by gently pressing on the body of the bottle. After instillation, tightly screw the cap back on and store the medication according to the recommendations provided in the instructions. Ophthalmic drops should be used with strict adherence to hygiene rules. Do not allow the tip of the dropper to touch any surface.

Dosage

For adults, instill 1 drop of 0.25% timolol solution (use timolol preparation at the appropriate concentration) into the affected eye(s) twice daily. If the response is inadequate, 0.5% solution should be used. If intraocular pressure is not adequately controlled, concomitant therapy with miotics, epinephrine, or systemic carbonic anhydrase inhibitors may be initiated. If satisfactory reduction of intraocular pressure is achieved during treatment, maintenance therapy with 1 drop per day should be continued.

Method of Administration

The drops should be instilled by pulling down the lower eyelid.

The bottle must remain closed when the patient is not using the medication.

Systemic absorption is reduced by nasolacrimal occlusion or by closing the eyes for 2 minutes after instillation. This may result in reduced systemic side effects and increased local activity.

Children

The safety and efficacy of Oftimol® in children have not been established.

Overdose

There is no specific data on overdose with this medication. In case of overdose with Oftimol®, treatment should be supportive and symptomatic. Accidental ingestion of the bottle contents may cause symptoms of beta-blocker overdose, including bradycardia, hypotension, heart failure, and bronchospasm.

In case of overdose, the following measures should be taken:

1. If the drug has been ingested orally — administer activated charcoal. Studies have shown that timolol maleate is not effectively removed by hemodialysis.
2. Symptomatic bradycardia: administer intravenous atropine sulfate in doses of 0.25 to 2 mg to induce vagal blockade. If bradycardia persists, carefully administer intravenous isoprenaline hydrochloride. In refractory cases, consider the use of a cardiac pacemaker.
3. Hypotension: use sympathomimetic agents such as dopamine, dobutamine, or noradrenaline. In refractory cases, glucagon may be beneficial.
4. Bronchospasm: administer isoprenaline hydrochloride. Concomitant therapy with aminophylline may be considered.
5. Acute heart failure: initiate immediate conventional therapy with digitalis glycosides, diuretics, and oxygen. In refractory cases, intravenous aminophylline is recommended.

If necessary, glucagon may subsequently be administered, which is also effective.

1. Heart block: administer isoprenaline hydrochloride or use a cardiac pacemaker.

Adverse reactions.

During clinical trials of timolol, the adverse reactions listed below were reported and classified as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Summary of safety profile

The most common adverse reactions during clinical trials with timolol were eye redness and eye irritation, occurring in approximately 5% and 2% of patients, respectively.

Additional adverse reactions identified during the post-marketing surveillance period were as follows. Based on available data, the frequency of their occurrence cannot be estimated.

Within each organ system class, adverse reactions are listed in order of decreasing severity.

Description of specified adverse reactions

As with other topical ophthalmic preparations, timolol is absorbed systemically. This may result in adverse events similar to those observed with systemic beta-blockers. The incidence of systemic adverse reactions following topical ophthalmic administration is lower than with systemic administration. The specified adverse reactions include those observed within the class of ophthalmic beta-blockers. Additional adverse reactions have been reported with the use of ophthalmic beta-blockers and may possibly occur with the use of Oftimol®:

Immune system disorders: systemic lupus erythematosus, systemic allergic reactions including angioedema, urticaria; localized and generalized rash, pruritus, anaphylactic reaction.

Metabolism and nutrition disorders: hypoglycemia.

Psychiatric disorders: insomnia, depression, nightmares, memory loss.

Nervous system disorders: syncope, stroke, cerebral ischemia, exacerbation of signs and symptoms of myasthenia gravis, dizziness, paresthesia, and headache.

Eye disorders: signs and symptoms of ocular irritation (e.g., burning, stinging, itching, tearing, redness), blepharitis, keratitis, blurred vision, and choroidal detachment following trabeculotomy (see section "Special precautions"), decreased corneal sensitivity, dry eye, corneal erosion, ptosis, diplopia, visual disturbances including changes in refraction (in some cases due to discontinuation of miotic therapy).

Ear and labyrinth disorders: tinnitus.

Cardiac disorders: bradycardia, chest pain, palpitations, edema, arrhythmia, congestive heart failure, atrioventricular block, cardiac arrest, heart failure.

Vascular disorders: hypotension, Raynaud's phenomenon, cold extremities.

Respiratory, thoracic and mediastinal disorders: bronchospasm (particularly in patients with a history of bronchial or pulmonary disease), dyspnea, cough, respiratory failure.

Gastrointestinal disorders: altered taste sensations, nausea, dyspepsia, diarrhea, dry mouth, abdominal pain, vomiting.

Skin and subcutaneous tissue disorders: alopecia, psoriasiform rash or exacerbation of psoriasis, skin rashes.

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

Reproductive system and breast disorders: sexual dysfunction (impotence), decreased libido.

General disorders and administration site conditions: general weakness/fatigue.

The following adverse reactions have been reported with systemic timolol therapy: limb pain, decreased exercise tolerance, increased sweating, exfoliative dermatitis, somnolence, urinary retention, hyperglycemia, non-specific thrombocytopenic purpura, Peyronie's disease.

Shelf life.

3 years. After opening, the product is stable for 28 days.

Do not use the product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging. 5 ml or 10 ml in a bottle, placed in a carton.

Prescription status. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's name and address of the place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.