Instructions for Dorzoptic Combi Eco eye drops 20+5mg/ml 5 ml
Composition
active ingredients: dorzolamide, timolol;
1 ml of eye drops, solution, contains 20 mg of dorzolamide (as 22.26 mg of dorzolamide hydrochloride) and 5 mg of timolol (as 6.83 mg of timolol maleate);
excipients: hydroxyethylcellulose, mannitol (E 421), sodium citrate, sodium hydroxide, water for injections.
Dosage form
Eye drops, solution.
Main physicochemical properties: transparent, slightly viscous, colorless aqueous solution.
Pharmacotherapeutic group
Drugs used in ophthalmology. Antiglaucoma drugs and miotics. Beta-adrenergic blockers.
ATX code S01E D51.
Pharmacological properties
Pharmacodynamics
The drug contains two active ingredients: dorzolamide hydrochloride and timolol maleate. Each of these components reduces elevated intraocular pressure by reducing the secretion of intraocular fluid, but the mechanism of action is different.
Dorzolamide hydrochloride is a potent inhibitor of type II carbonic anhydrase. Inhibition of miliary carbonic anhydrase reduces aqueous humor secretion by slowing the formation of bicarbonate ions, which in turn reduces sodium and fluid transport.
Timolol maleate is a non-selective beta-adrenergic receptor blocker. The exact mechanism of action of timolol, which is manifested in the reduction of intraocular pressure, is still unknown. Fluorimetric and tonographic studies indicate that the effect of timolol is due to a decrease in the secretion of humoral fluid. In addition, timolol may increase the outflow of moisture.
The combined effect of the two components causes a more pronounced reduction in intraocular pressure than with monotherapy with these drugs.
After topical application, Dorzoptic Combi Eco reduces intraocular pressure, regardless of whether its increase is associated with glaucoma. Increased intraocular pressure plays a significant role in the pathogenesis of optic nerve damage and visual field loss in glaucoma.
Dorzoptic Combi Eco reduces intraocular pressure without the development of side effects typical of miotic agents, such as night blindness, accommodation spasm, and pupil constriction.
Pharmacokinetics
Dorzolamide hydrochloride. When applied topically, dorzolamide penetrates the systemic circulation. With prolonged use, dorzolamide accumulates in erythrocytes as a result of binding to carbonic anhydrase type II, maintaining very low concentrations of the free drug in plasma. As a result of metabolism, dorzolamide forms a single N-desethyl metabolite, which blocks carbonic anhydrase type II less strongly than its original form, but incubates carbonic anhydrase type I, a less active isoenzyme. The metabolite also accumulates in erythrocytes, where it binds mainly to carbonic anhydrase type I. Approximately 33% of dorzolamide binds to plasma proteins. Dorzolamide is excreted in the urine in unchanged form and as a metabolite. After discontinuation of the drug, dorzolamide is eliminated from erythrocytes in a non-linear manner, with an initial rapid decline in concentration followed by a slow elimination phase with a half-life of approximately 4 months.
Timolol maleate. Timolol is absorbed systemically after topical ocular administration. Systemic exposure to timolol was determined after topical application of a 0.5% ophthalmic solution twice daily. Peak plasma concentrations were 0.46 ng/mL after the morning dose and 0.35 ng/mL after the evening dose.
Indication
Increased intraocular pressure in patients with open-angle glaucoma or pseudoexfoliative glaucoma when topical beta-blockers alone are insufficient.
Contraindication
Hypersensitivity to one or both active substances or to any of the components of the medicinal product;
respiratory tract diseases, including bronchial asthma, and a history of bronchial asthma or severe chronic obstructive pulmonary disease;
sinus bradycardia, sinoatrial node weakness syndrome, second or third degree atrioventricular block not controlled by a pacemaker, severe heart failure, cardiogenic shock;
severe renal impairment (creatinine clearance < 30 ml/min) or hyperchloremic acidosis;
Interaction with other medicinal products and other types of interactions
However, there is a possibility of additive effects resulting in hypotension and/or marked bradycardia when timolol maleate is used concomitantly with oral calcium channel blockers, catecholamine-reducing agents or beta-adrenergic receptor blockers, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, guanethidine, narcotics and monoamine oxidase inhibitors (MAOIs).
Potentiation of systemic beta-blockade (decreased heart rate, depression) has been reported when timolol is used concomitantly with CYP2D6 inhibitors (e.g. quinidine-type selective serotonin reuptake inhibitors).
Dorzolamide, one of the components of the drug, is a carbonic anhydrase inhibitor and can be absorbed systemically when applied topically. Although studies have not demonstrated an effect of dorzolamide in the form of eye drops on acid-base balance, such an effect is known with the use of oral forms of carbohydrase inhibitors, which in some cases caused toxicity when taking high doses of salicylates. Therefore, the possibility of interaction should be considered in patients using the drug Dorzoptic Combi Eco.
Although Dorzoptic Combi Eco has little effect on pupil size when used as monotherapy, mydriasis has occasionally been reported following concomitant use of topical timolol maleate and epinephrine (adrenaline).
Beta-blockers may enhance the hypoglycemic effects of antidiabetic drugs.
Oral beta-blockers may provoke the development of "rebound" arterial hypertension upon withdrawal of clonidine.
Application features
Before using the medicine, wash your hands thoroughly.
Reactions from the cardiovascular and respiratory systems
Like other topical ophthalmic drugs, timolol is absorbed systemically. Since timolol is a beta-blocker, cardiovascular and respiratory adverse reactions similar to those seen with systemic beta-blockers may occur. The incidence of systemic adverse reactions following topical ophthalmic drugs is lower than with systemic use. For reduced systemic absorption, see section 4.2.
Cardiac disorders
Before prescribing beta-blockers to patients with cardiovascular disease (e.g. coronary artery disease, vasospastic angina/Prinzmetal's angina, heart failure) and arterial hypotension, the appropriateness of such treatment should be seriously assessed and treatment with other active substances should be considered. Patients with cardiovascular disease should be monitored for signs of worsening of these conditions and for adverse reactions.
Due to the negative effect on impulse conduction time, beta-blockers should be prescribed with caution in patients with first-degree heart block.
Vascular disorders
Patients with severe peripheral/circulatory disorders (i.e. severe Raynaud's disease or Raynaud's syndrome) should be treated with caution.
Respiratory system disorders
Respiratory reactions, including death due to bronchospasm, have been reported in patients with asthma following the use of some ophthalmic beta-blockers.
Dorzoptic Combi Eco should be used with caution in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only if the expected benefit outweighs the potential risk.
Liver dysfunction.
Since there are no data on the use of the drug in patients with impaired liver function, Dorzoptic Combi Eco should be prescribed with caution to such patients.
Immunological and hypersensitivity reactions.
Like other topical agents, Dorzoptic Combi Eco can be absorbed systemically. Dorzolamide, like sulfonamides, contains a sulfonamide group, therefore, the development of adverse reactions observed with systemic use of sulfonamide drugs is possible, including such severe reactions as Stevens-Johnson syndrome and toxic epidermal necrolysis. If signs of serious reactions or hypersensitivity reactions appear, the drug should be discontinued.
When using Dorzoptic Combi Eco, local adverse reactions from the organs of vision were observed, similar to those observed with dorzolamide hydrochloride. If such reactions develop, the use of Dorzoptic Combi Eco should be discontinued.
When taking beta-blockers, patients with atopy or a history of severe anaphylactic reactions to multiple allergens may be more sensitive to re-exposure to such allergens and may not respond to treatment of anaphylactic reactions with usual doses of adrenaline.
Concomitant therapy.
The use of dorzolamide and oral carbonic anhydrase inhibitors is not recommended.
Discontinuation of treatment.
As with systemic beta-blockers, ophthalmic timolol should be tapered off if discontinuation is necessary in patients with coronary artery disease.
Additional effects of beta-blockers.
Hypoglycemia/diabetes
Beta-blockers should be used with caution in patients prone to spontaneous hypoglycemia and in patients with labile diabetes mellitus, as beta-blockers may mask the symptoms of acute hypoglycemia.
Beta-blockers may also mask the signs of hyperthyroidism. Abrupt discontinuation of beta-blockers may result in worsening of symptoms.
Corneal diseases
Ophthalmic beta-blockers may cause dry eyes. Patients with corneal diseases should be treated with caution.
Anesthesia for surgery
Ophthalmic beta-blockers may block the systemic effects of beta-agonists, such as adrenaline. The anaesthetist should be informed that the patient is receiving timolol.
Treatment with beta-blockers may exacerbate symptoms of myasthenia gravis.
Additional effects of carbonic anhydrase inhibition.
Treatment with oral carbonic anhydrase inhibitors has been associated with the development of urolithiasis as a result of acid-base disturbances, especially in patients with a history of urolithiasis. Although acid-base disturbances have not been observed with Dorzoptic Combi Eco, urolithiasis has been reported rarely. Since Dorzoptic Combi Eco contains a carbonic anhydrase inhibitor that is absorbed systemically when applied topically, patients with a history of urolithiasis are at increased risk of urolithiasis when using this medicinal product.
Other features.
Treatment of patients with acute angle-closure glaucoma requires the use of other therapeutic agents in addition to drugs that lower intraocular pressure. This medicinal product has not been studied in patients with acute angle-closure glaucoma.
Corneal edema and irreversible corneal decompensation have been reported with dorzolamide in patients with pre-existing chronic corneal defects and/or a history of intraocular surgery. There is a high probability of corneal edema. Precautions should be taken when prescribing Dorzoptic Combi Eco to such groups of patients.
Choroid detachment has been reported following filtration procedures with treatment with aqueous suppressants (e.g., timolol, acetazolamide).
As with other antiglaucoma drugs, decreased sensitivity to ophthalmic timolol maleate has been reported after long-term treatment in some patients. However, in clinical trials in which 164 patients were followed for at least three years, no significant change in mean intraocular pressure was observed after initial stabilization of pressure.
Treatment of patients with acute open-angle glaucoma requires the use of other therapeutic agents in addition to drugs that lower intraocular pressure. The use of Dorzoptic Combi Eco in patients with acute open-angle glaucoma has not been studied.
Using contact lenses.
The effect of dorzolamide/timolol has not been studied in patients wearing contact lenses. Contact lenses should be removed before instillation of the drug and should not be reinserted until 15 minutes after application.
Use during pregnancy or breastfeeding
Pregnancy
Dorzoptic Combi Eco should not be used during pregnancy.
Dorzolamide
There are no relevant clinical data on exposure during pregnancy. Dorzolamide was teratogenic in rabbits at doses toxic to the mother.
Timolol
There are no adequate data from the use of timolol in pregnant women. Timolol should not be used during pregnancy unless clearly necessary.
Epidemiological studies have not shown any malformative effect, but such studies have shown a risk of intrauterine growth retardation with oral beta-blockers. In addition, symptoms of beta-blockade (such as bradycardia, hypotension, dyspnea (shortness of breath) and hypoglycemia) have been observed in neonates when beta-blockers were used antepartum. If this drug is used antepartum, the neonate should be closely monitored during the first days of life.
Breast-feeding
It is not known whether dorzolamide is excreted in human milk. In studies in lactating rats treated with dorzolamide, decreased body weight of pups was observed.
Beta-blockers are excreted in breast milk. However, at therapeutic doses of timolol in eye drops, it is unlikely that breast milk contains enough of it to cause clinical symptoms of beta-blockade in the infant. If treatment with Dorzoptic Combi Eco is necessary, breast-feeding is not recommended.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effects of the drug on the ability to drive and use machines have not been conducted. Possible side effects, such as blurred vision, may adversely affect the ability of some patients to drive and use machines.
Method of administration and doses
Dorzoptic Combi Eco is applied 1 drop into the conjunctival sac twice a day.
If several topical ophthalmic drugs are used in the treatment, they should be administered with an interval of 10 minutes. If switching from treatment with other ophthalmic drugs to the use of the drug Dorzoptic Combi Eco, it is used the next day after the cancellation of the previous drug.
The patient should be warned to wash their hands before use and not to touch the eye and surrounding areas with the pipette.
In case of simultaneous use of another local ophthalmic drug, Dorzoptic Combi Eco should be applied with an interval of at least 10 minutes.
Patients should also be informed that improper handling of eye drops can introduce bacteria into the solution, which can cause eye infections. Using contaminated solutions can cause serious damage and loss of vision.
Application of Dorzoptic Combi Eco drops:
1. Wash your hands thoroughly before using the drug.
2. If the packaging or bottle is damaged, do not use the drops.
3. Make sure that the sealing ring on the lid is not damaged. Before first use, unscrew the lid: you may feel a slight resistance when breaking the sealing ring.
4. If the warranty ring is damaged during the first opening, it should be removed and discarded to avoid injury.
5. Tilt the head back and gently pull the lower eyelid down to create a space between the eyeball and the eyelid. Avoid contact between the dropper tip and the eye, eyelids or fingers.
6. Gently squeeze the sides of the bottle and let the drops fall into your eye. Please note that there may be a delay of a few seconds between squeezing the bottle and the drop coming out. Do not press too hard. If you are not sure how to put in the drops, ask your doctor, pharmacist or nurse.
7. Then apply pressure to the nasolacrimal duct for approximately 2 minutes (by pressing your finger on the corner of the eye near the nose), close your eyes and keep them closed for this time. This may result in reduced systemic side effects and increased local activity.
8. Do not touch the dropper tip to the surface of the eye or surrounding tissues.
9. If the doctor has prescribed the use of the drug in the conjunctival sac of the other eye, it is necessary to repeat points 5–6 and 7.
10. After use and before re-use, shake the bottle once, holding the bottle with the tip down, without touching the dropper tip, to remove any remaining solution in the tip. This is necessary to ensure the delivery of subsequent drops. After instillation, screw the cap back on the bottle.
If the drop does not reach the patient's eye, you should try again.
Children
The drug Dorzoptic Combi Eco is not used in children, as there is no data on efficacy and safety for pediatric patients.
Overdose
There is no information on accidental or intentional overdose of Dorzoptic Combi Eco by ingestion. In case of an overdose of timolol, the development of systemic effects of an overdose of systemic beta-blockers is possible: dizziness, headache, shortness of breath, bradycardia, bronchospasm and cardiac arrest. The most expected symptoms of an overdose of dorzolamide are electrolyte imbalance, development of acidosis and effects on the central nervous system.
There are some reports of accidental or intentional overdose with dorzolamide hydrochloride. Drowsiness has been reported after oral administration. The following symptoms have been observed with topical administration: nausea, dizziness, headache, weakness, abnormal dreams, dysphagia.
Treatment: symptomatic and supportive. Monitoring of serum electrolyte levels (mainly potassium) and blood pH. Timolol is not completely removed by dialysis.
Side effects
The following adverse reactions have been reported with Dorzoptic Combi Eco or one of its components. Frequency: 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), not known (cannot be estimated from the available data).
Immune system disorders
Dorzolamide with timolol
Rare: signs and symptoms of systemic allergic reactions, including angioedema, urticaria, pruritus, rash, anaphylactic reaction.
Timolol maleate, eye drops, solution
Rare: signs and symptoms of allergic reactions, including angioedema, urticaria, focal and multiple rashes, anaphylactic reaction.
Not known**: itching.
Metabolic and nutritional disorders
Timolol maleate, eye drops, solution
Not known**: hypoglycemia.
Mental disorders
Timolol maleate, eye drops, solution
Uncommon: depression*.
Uncommon: insomnia*, nightmares, memory loss.
Not known: hallucinations.
Nervous system disorders
Common: headache*.
Uncommon: dizziness*, paresthesia*.
Timolol maleate, eye drops, solution
Common: headache*.
Uncommon: dizziness*, syncope*.
Rare: paresthesia*, increased symptoms of myasthenia gravis, decreased libido*, hemorrhagic stroke*, cerebral ischemia.
Visual impairment
Dorzolamide with timolol
Very common: burning and tingling.
Common: conjunctival injection, blurred vision, corneal erosion, eye itching, lacrimation.
Dorzolamide hydrochloride, eye drops, solution
Common: eyelid inflammation*, eyelid irritation*.
Uncommon: iridocyclitis*.
Rare: eye irritation, including redness*, eye pain*, eyelid peeling*, transient myopia (reversible upon discontinuation of treatment), corneal edema*, decreased intraocular pressure*, choroid detachment (requiring filtration surgery)*, foreign body sensation.
Timolol maleate, eye drops, solution
Common: signs and symptoms of eye irritation, including blepharitis*, keratitis*, decreased corneal sensitivity, dry eyes*.
Uncommon: visual disturbances, including refractive errors (in some cases due to withdrawal of miotics)*.
Rare: ptosis, diplopia, choroid detachment requiring filtration surgery* (see section "Special warnings and precautions for use").
Not known: itching, tearing, redness, blurred vision, corneal erosion.
Hearing and balance disorders
Timolol maleate, eye drops, solution
Rare: ringing in the ears*.
Cardiac disorders
Timolol maleate, eye drops, solution
Uncommon: bradycardia*.
Rare: chest pain*, palpitations*, edema*, arrhythmia*, congestive heart failure*, cardiac arrest*, heart block.
Not known: atrioventricular block, heart failure, palpitations.
Dorzolamide hydrochloride, eye drops, solution
Not known: tachycardia.
Vascular disorders
Timolol maleate, eye drops, solution
Rare: hypotension*, claudication, Raynaud's phenomenon*, feeling of coldness in the hands and feet*.
Dorzolamide hydrochloride, eye drops, solution
Not known: hypertension.
Respiratory, thoracic and mediastinal disorders
Dorzolamide with timolol
Common: sinusitis.
Rare: shortness of breath, respiratory failure, rhinitis, bronchospasm.
Dorzolamide hydrochloride, eye drops, solution
Uncommon: epistaxis*.
Timolol maleate, eye drops, solution
Uncommon: difficulty breathing (dyspnea)*.
Rare: bronchospasm (predominantly in patients with pre-existing bronchospastic disease)*, respiratory failure, cough*.
Gastrointestinal disorders
Dorzolamide with timolol
Very common: dysgeusia (change in taste).
Dorzolamide hydrochloride, eye drops, solution
Common: nausea*.
Uncommon: throat irritation, dry mouth*
Timolol maleate, eye drops, solution
Uncommon: nausea*, dyspepsia*
Uncommon: diarrhoea, dry mouth*
Not known: dysgeusia (change in taste), abdominal pain, vomiting.
Skin and subcutaneous tissue disorders
Dorzolamide with timolol
Rare: contact dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Dorzolamide hydrochloride, eye drops, solution
Rare: rash*.
Timolol maleate, eye drops, solution
Rare: alopecia*, psoriatic rash or exacerbation of psoriasis*.
Not known: skin rash.
Musculoskeletal and connective tissue disorders
Timolol maleate, eye drops, solution
Isolated: systemic lupus erythematosus.
Not known: myalgia.
Renal and urinary disorders
Dorzolamide with timolol:
Uncommon: urolithiasis.
Genital and mammary disorders
Timolol maleate, eye drops, solution
Uncommon: Peyronie's disease*, decreased libido.
Not known: sexual dysfunction.
General disorders and administration site conditions
Dorzolamide hydrochloride, eye drops, solution
Common: asthenia/weakness*.
Timolol maleate, eye drops, solution
Uncommon: asthenia/weakness*
* Adverse reaction observed after use of dorzolamide with timolol.
**Additional adverse reactions that have been observed with ophthalmic beta-blockers and may occur with the drug.
Expiration date
2 years. Do not use after the expiry date stated on the packaging.
The shelf life after first opening is 90 days.
Keep the bottle tightly closed.
Storage conditions
Store at a temperature not exceeding 30 ° C. Store in the original packaging.
Chemical and physical stability has been demonstrated for 90 days at 25 ± 2ºC.
From a microbiological point of view, once opened, the medicinal product may be stored for a maximum of 90 days at a temperature not exceeding 25 ºC. Other storage times and conditions during use are the responsibility of the consumer.
Keep out of reach of children.
Packaging
5 ml of solution in a 5 ml polyethylene dropper bottle with a cap with a guarantee ring. 1 or 3 bottles in a cardboard box.
Vacation category
According to the recipe.
Producer
Rafarm S.A.
Location of the manufacturer and its business address
Tesi Pusi Hatzi Agiou Louka, Payania, 190 02, Greece
Thesi Pousi Xatzi Agiou Louka, Paiania, 190 02, Greece
