Instructions for use Dorzotymol eye drops solution dropper bottle 5 ml
Composition
active ingredients: dorzolamide and timolol;
5 ml of solution contains dorzolamide hydrochloride 0.11125 g, equivalent to 0.10001 g of dorzolamide, and timolol maleate 0.03416 g, equivalent to 0.02499 g of timolol;
Excipients: benzalkonium chloride, mannitol (E 421), sodium citrate, sodium hydroxide, hydroxyethylcellulose, purified water.
Dosage form
Eye drops, solution.
Main physicochemical properties: transparent and colorless or almost colorless liquid.
Pharmacotherapeutic group
Drugs used in ophthalmology. Antiglaucoma drugs and miotics. Beta-adrenergic blockers. Timolol, combinations.
ATX code S01E D51.
Pharmacological properties
Pharmacodynamics
Dorzotymol® contains two components, dorzolamide and timolol. Both components lower intraocular pressure by reducing the secretion of aqueous humor, but their mechanisms of action are different.
Dorzolamide is a potent inhibitor of carbonic anhydrase II in humans. By inhibiting carbonic anhydrase in the ciliary body, it reduces the secretion of aqueous humor by slowing the formation of bicarbonate ions, with a subsequent decrease in sodium and fluid concentrations.
Timolol is a non-selective beta-adrenergic receptor blocker. The exact mechanism by which timolol reduces intraocular pressure is not fully understood, although fluorescein staining and computed tomography studies suggest a reduction in aqueous humor production. However, some studies have shown a small increase in aqueous humor production. The combined action of dorzolamide and timolol results in a greater reduction in intraocular pressure than either agent alone.
Topical application of Dorzotymol® eye drops reduces elevated intraocular pressure, whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and visual field loss due to glaucoma. Intraocular pressure is reduced without the usual side effects of miotics, such as night blindness, accommodation spasm, and pupillary constriction.
Pharmacokinetics
Unlike oral carbonic anhydrase inhibitors, topical dorzolamide acts directly on the eye, even in small doses, thereby reducing its systemic effects. Clinical studies have shown that this method can reduce intraocular pressure without disturbing the acid-base and electrolyte balance as occurs with carbonic anhydrase inhibitors.
Dorzolamide enters the peripheral circulation also when applied topically. To assess the extent of systemic inhibition of carbonic anhydrase when applied topically, the concentration of the active substance and metabolites in plasma and erythrocytes, as well as the inhibition of carbonic anhydrase activity in erythrocytes, were determined. Dorzolamide accumulates in erythrocytes during prolonged use due to selective binding to carbonic anhydrase type II, and in plasma in free form it is stored in very low concentrations. One N-diethyl metabolite is formed from the active substance, which inhibits the activity (carbonic anhydrase type II) less weakly than the active substance, but also inhibits the activity of the less active isoenzyme (carbonic anhydrase type I). The metabolite also accumulates in erythrocytes, where it binds approximately initially to carbonic anhydrase type I. Dorzolamide is approximately 33% bound to plasma proteins. It is excreted primarily in the urine, unchanged. The metabolite is also excreted in the urine. After discontinuation of the drug, dorzolamide is eliminated non-linearly from erythrocytes, and elimination is characterized by an initial rapid decline in the concentration of this component and a subsequent slow phase with a half-life of approximately 4 months.
In a plasma concentration study, systemic exposure to timolol was observed in 6 patients after topical administration of timolol 0.5% eye drops twice daily. The mean maximum plasma concentration after the morning dose was 0.46 ng/ml and 0.35 ng/ml after the afternoon dose.
Indication
Dorzotymol® is used to treat elevated intraocular pressure in patients with:
open-angle glaucoma; pseudoexfoliative glaucoma;
as adjunctive therapy to beta-blocker treatment or as monotherapy when beta-blocker treatment has not been successful or beta-blockers are contraindicated.
Contraindication
Dorzotymol® drops are contraindicated in patients:
with hypersensitivity to one or both active substances or to any of the excipients; with reactive airway disease, including bronchial asthma, and a history of bronchial asthma or with severe obstructive pulmonary disease; with sinus bradycardia, sick sinus syndrome, sinoatrial block, atrioventricular block II and III degree not controlled by a pacemaker, severe heart failure, cardiogenic shock; with severe renal impairment (creatinine clearance <30 ml/min) and hyperchloremic acidosis.
Interaction with other medicinal products and other types of interactions
oral carbonic anhydrase inhibitors; other topical beta-adrenergic blockers.
During clinical trials, Dorzotymol® was used concomitantly with the following medications, and no adverse interactions were observed with ACE inhibitors, calcium channel blockers, diuretics, nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, and hormones (e.g. estrogen, insulin, and thyroxine).
However, there is a possibility of additive effects and hypotension and/or marked bradycardia when timolol maleate is used concomitantly with oral calcium channel blockers, drugs that reduce catecholamine production or beta-adrenergic receptor blockers, antiarrhythmic drugs (including amiodarone), digitalis glycosides, parasympathomimetics, narcotics and monoamine oxidase inhibitors.
Cases of systemic effects of beta-blockers (e.g., heart rate slowing, depression) have been reported with concomitant use of CYP2D6 inhibitors (quinidine, selective serotonin reuptake inhibitors) and timolol.
Despite the fact that with Dorzotymol® monotherapy the effect on the pupil is minimal or absent, there are isolated cases of mydriasis with the combined use of timolol maleate and adrenaline.
Beta-blockers may enhance the hypoglycemic effect of antidiabetic drugs.
Discontinuation of clonidine may cause exacerbation of hypertension, and taking beta-blockers may further exacerbate it.
Application features
Reactions from the cardiovascular and respiratory systems.
As with all topical ophthalmic drugs, the drug may also be absorbed systemically. Timolol is a beta-blocker, therefore, with topical use, all the side effects that are also observed with systemic use of beta-blockers are possible, including exacerbation of Prinzmetal's angina, exacerbation of severe circulatory disorders and arterial hypotension, heart failure. Patients with cardiovascular disease should be monitored for signs of deterioration and adverse reactions. Respiratory and cardiac reactions have been reported with timolol, including a fatal case due to bronchospasm in a patient with asthma, as well as rare deaths associated with heart failure. Respiratory reactions due to bronchospasm have been reported in patients with asthma after the use of some ophthalmic beta-blockers. Dorzotymol should be used with caution in patients with mild/moderate chronic obstructive pulmonary disease and only if the expected benefit outweighs the potential risk.
Patients with severe peripheral vascular or circulatory disorders (i.e. severe Raynaud's disease or Raynaud's syndrome) should be treated with caution.
Liver dysfunction
The use of Dorzotymol® in patients with impaired liver function has not been studied, therefore it should be used with caution in such patients.
Immunological and hypersensitivity reactions
Like all topically applied ophthalmic drugs, the drug can also be absorbed systemically. Dorzolamide, like sulfonamides, contains a sulfonamide group. Therefore, with topical use, side effects are possible that are also observed with systemic use of sulfonamide drugs. If signs of acute reactions or hypersensitivity appear, the drug should be discontinued.
Local ocular adverse reactions similar to those seen with dorzolamide eye drops have been reported. If such reactions occur, discontinuation of Dorzotymol® should be considered.
Patients with atopy or a history of acute anaphylactic reactions to various allergens may be sensitive to repeated accidental, diagnostic or therapeutic exposure to these allergens while taking beta-blockers. It is also possible that such patients will not respond to the usual doses of adrenaline used in anaphylactic reactions. The anaesthetist should be informed that the patient is receiving timolol.
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 discontinuation
As with systemic beta-blocker use, topical timolol should be administered gradually to patients with coronary heart disease.
Additional effects of beta-blockers
Beta-blocker therapy may mask some of the symptoms of hypoglycemia in diabetic patients and patients with hypoglycemia. Beta-blockers should be used with caution in patients prone to spontaneous hypoglycemia or in patients with labile diabetes.
Beta-blocker treatment may mask some symptoms of hyperthyroidism. Abruptly stopping beta-blocker use may worsen symptoms or cause new ones to appear.
Treatment with beta-blockers may exacerbate the symptoms of myasthenia gravis.
Ophthalmic beta-blockers may cause dry eyes. Patients with corneal diseases should be treated with caution.
Oral administration of carbonic anhydrase inhibitors has been associated with urolithiasis due to acid-base disturbances, particularly in patients with a history of kidney stones. Although no acid-base disturbances have been observed with Dorzotymol® eye drops, there have been isolated cases of urolithiasis.
Because Dorzotymol® contains a topical carbonic anhydrase inhibitor that is absorbed systemically, patients with a history of kidney stones are at increased risk of developing urolithiasis.
Other
Patients with acute angle-closure glaucoma also require the use of other medications along with those used to lower intraocular pressure. The use of Dorzotymol® in patients with acute angle-closure glaucoma has not been studied.
There have been reports of corneal edema and irreversible corneal decompensation in patients with chronic corneal disease or patients who have undergone ocular surgery and have received dorzolamide. Dorzolamide topical should be used with caution in these patients.
Corneal peeling has been observed after filtration surgery in patients taking medications to prevent tearing.
Cases of insensitivity to timolol have been reported with long-term ophthalmic use. In clinical studies in which 164 patients were followed for at least 3 years, there was no statistically significant difference in mean intraocular pressure after initial stabilization.
Using contact lenses
Dorzotymol® eye drops contain the preservative benzalkonium chloride, which may cause eye irritation. Contact lenses should be removed before using the drops and should not be reinserted until 15 minutes have passed. Benzalkonium chloride is known to discolour contact lenses.
Ability to influence reaction speed when driving vehicles or other mechanisms
Some patients may experience side effects, such as blurred vision, which may affect their ability to drive and use machines.
Use during pregnancy or breastfeeding
The drug is not used during pregnancy.
It is not known whether dorzolamide is excreted in human milk. Timolol is excreted in human milk. Therefore, breastfeeding should be discontinued during treatment.
Method of administration and doses
In the case of monotherapy, it is recommended to instill 1 drop of Dorzotymol® into the conjunctival sac of the affected eye twice a day. In the case of topical application of several ophthalmic agents, a break of 10 minutes should be taken.
Patients should be advised to wash their hands before use and not to touch the eye or surrounding surfaces with the pipette.
Patients should also be informed that if eye drops are handled improperly, these solutions can become contaminated with bacteria that cause eye infections. If a contaminated solution is used, severe damage with subsequent loss of vision is possible.
Elderly patients
The indicated dosage also applies to elderly patients.
Application procedure.
Instill 1 drop into the medial canthus of each eye. Press lightly on the lacrimal sac area immediately after instillation to reduce the possibility of systemic absorption of Dorzotymol®.
Children
The medicine is not used in children.
Overdose
There are no data on overdose of timolol with dorzolamide associated with oral administration.
Symptoms
Reports of accidental overdose with timolol eye drops have shown systemic effects similar to those seen with systemic beta-blockers, such as: clouding of vision, headache, shallow breathing, bradycardia, bronchospasm and cardiac arrest. The most common symptoms to be expected with dorzolamide overdose are electrolyte imbalance, acidosis and central nervous system effects.
Drowsiness has been observed with accidental oral administration.
Nausea, dizziness, headache, fatigue, abnormal dreams, and dysphagia have been reported with topical use.
Data on overdose of dorzolamide when administered orally are limited. Drowsiness has been observed with oral administration. Nausea, dizziness, headache, fatigue, abnormal dreams and dysphagia have been observed with topical administration.
Treatment
Treatment of overdose should be symptomatic and supportive. Serum electrolytes (especially potassium) and blood pH should be monitored. Studies have shown that timolol is not removed by dialysis.
Adverse reactions
During clinical trials, side effects that have already been observed with dorzolamide and/or timolol were observed.
Clinical trials included 1035 patients. Approximately 2.4% of them discontinued treatment due to visual side effects and approximately 1.2% of patients discontinued treatment due to local reactions related to allergy or hypersensitivity (e.g. eyelid inflammation and conjunctivitis).
The following adverse reactions were observed during clinical trials and in the post-marketing period with the following frequencies:
very common: ≥ 1/10; common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1000 to < 1/100; rare: ≥ 1/10,000 to < 1/1000.
Rare: symptoms of systemic allergic reactions, including angioedema, urticaria, itching, rash, anaphylactic reaction.
Disorders of the musculoskeletal system and connective tissues.
Timolol maleate, eye drops, solution.
Rare: systemic lupus erythematosus.
From the nervous system.
Dorzolamide, eye drops, solution.
Common: headache
Rare: dizziness, paresthesia.
Timolol maleate, eye drops, solution.
Common: headache
Uncommon: dizziness.
Rare: loss of consciousness, paresthesia, symptoms of myasthenia gravis, decreased libido, hemorrhagic stroke, cerebral ischemia.
Psychiatric disorders.
Timolol maleate, eye drops, solution.
Uncommon: depression.
Rare: insomnia, nightmares, memory loss.
From the organs of vision.
Combination of timolol with dorzolamide
Very common: tingling and burning.
Common: conjunctival infection, blurred vision, corneal erosion, eye itching, lacrimation.
Dorzolamide, eye drops, solution.
Common: eyelid inflammation, eyelid irritation.
Uncommon: iridocyclitis.
Rare: irritation, including redness, eye pain, eyelid peeling, temporary myopia (reversible after discontinuation of treatment), corneal edema, decreased intraocular pressure, ablation of uveitis (after filtration surgery).
Timolol maleate, eye drops, solution.
Common: symptoms of eye irritation, including blepharitis, keratitis, decreased corneal sensitivity, dry eye.
Uncommon: visual disturbances, including changes in light refraction (due to discontinuation of miotic treatment in some cases).
Rare: ptosis, diplopia, uveitis ablation (after filtration surgery)
Not known: itching, tearing, redness, blurred vision, corneal erosion.
From the side of the hearing organs.
Timolol maleate, eye drops, solution.
Rare: ringing in the ears.
Cardiovascular system disorders.
Timolol maleate, eye drops, solution.
Uncommon: bradycardia, syncope.
Rare: hypotension, chest pain, palpitations, edema, arrhythmia, congestive heart failure, heart block, cardiac arrest, cerebral ischemia, claudication, Raynaud's phenomenon, coldness in the hands and feet.
On the part of the respiratory system, chest and mediastinum.
Combination of timolol with dorzolamide
Common: sinusitis.
Rare: dyspnea, respiratory failure, rhinitis, bronchospasm.
Dorzolamide, eye drops, solution.
Rare: nosebleed.
Timolol maleate, eye drops, solution.
Uncommon: dyspnoea.
Rare: bronchospasm (predominantly in patients with pre-existing bronchospastic disease), cough.
From the digestive system.
Combination of timolol with dorzolamide.
Very common: taste disturbance.
Dorzolamide, eye drops, solution.
Common: nausea.
Rare: throat irritation, dry mouth.
Timolol maleate, eye drops, solution.
Uncommon: nausea, dyspepsia.
Rare: diarrhea, dry mouth.
On the part of the skin and subcutaneous tissues.
Combination of timolol with dorzolamide.
Rare: contact dermatitis, Stevens-Johnson syndrome, chronic epidermal necrolysis.
Dorzolamide, eye drops, solution.
Rare: rash.
Timolol, eye drops, solution.
Rare: alopecia, psoriasiform rash or exacerbation of psoriasis.
On the part of the kidneys and urinary system.
Combination of timolol with dorzolamide.
Uncommon: urolithiasis.
From the reproductive system and mammary glands.
Timolol maleate, eye drops, solution.
Rare: Peyronie's disease, decreased sexual desire.
General violations.
Dorzolamide, eye drops, solution.
Uncommon: asthenia/weakness.
Expiration date
2 years.
Storage conditions
Store out of the reach of children at a temperature not exceeding 30 ° C. After opening the bottle, eye drops should be used within 4 weeks.
Packaging
5 ml of solution in a dropper bottle; 1 dropper bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
Jadran- Galenski Laboratorij dd/Jadran- Galenski Laboratorij dd
Location of the manufacturer and its business address
Svilno 20, 51000 Rijeka, Croatia/ Svilno 20, 51000 Rijeka, Croatia
