Instructions for Lanotan T eye drops solution bottle 2.5 ml
Composition
active ingredients: latanoprost, timolol;
1 ml of the drug contains latanoprost 0.05 mg, timolol maleate in terms of timolol 100% substance 5 mg;
Excipients: benzalkonium chloride; sodium dihydrogen phosphate, monohydrate; sodium hydrogen phosphate anhydrous; sodium chloride; water for injections.
Dosage form
Eye drops, solution.
Main physicochemical properties: clear colorless liquid.
Pharmacotherapeutic group
Antiglaucoma drugs and miotics. Beta-blocking agents. Timolol, combinations. ATX code S01E D51.
Pharmacological properties
Pharmacodynamics.
Lanotan® T contains two active ingredients: latanoprost and timolol maleate. Both components reduce elevated intraocular pressure through different mechanisms of action, the combined effect leading to a more pronounced reduction in intraocular pressure compared to monotherapy with either of them. Latanoprost, a prostaglandin F2α analogue, is a selective agonist of prostaglandin FP receptors, which reduces intraocular pressure by increasing the outflow of aqueous humor. The main mechanism of action is to increase uveoscleral outflow. In addition, slightly increased outflow (decreased resistance to outflow in the trabeculae) has been reported in humans. Latanoprost does not significantly affect the production of aqueous humor and the blood-aqueous barrier or intraocular blood circulation. Long-term use of latanoprost in monkeys that underwent extracapsular lens extraction did not affect the retinal vessels according to fluorescein angiography. Latanoprost did not induce fluorescein leakage in the posterior segment of the eye in pseudophakic patients during a short course of treatment.
Timolol is a (non-selective) β1- and β2-adrenergic receptor blocker that has no significant direct sympathomimetic action, no direct myocardial depressant effect, and no membrane-stabilizing activity. Timolol reduces intraocular pressure by reducing the formation of aqueous humor in the ciliary epithelium. The exact mechanism of action has not been established, but inhibition of the increased synthesis of AMP caused by endogenous stimulation of β-adrenergic receptors is likely.
Timolol has no significant effect on the permeability of the blood-brain barrier to plasma proteins. In rabbits, timolol had no effect on local ocular blood flow after chronic administration.
Lanotan® T shows a significantly greater reduction in mean daytime intraocular pressure compared with latanoprost or timolol monotherapy when administered once daily. Evening administration may be more effective in reducing intraocular pressure than morning administration. However, the patient's lifestyle and likely compliance should be taken into account when considering morning or evening dosing recommendations.
It should be remembered that in case of insufficient effectiveness of the combined drug, it may be effective to prescribe timolol 2 times a day and latanoprost 1 time a day separately, which was confirmed during studies.
The onset of action of Lanotan® T occurs within 1 hour, and the maximum effect lasts from 6 to 8 hours. The effect of adequate reduction of intraocular pressure lasts up to 24 hours in case of repeated use.
Pharmacokinetics.
Latanoprost. Latanoprost is a prodrug of the isopropyl ester, which is essentially inactive, but after hydrolysis by the esters in the cornea becomes the biologically active acid of latanoprost. The prodrug is well absorbed through the cornea and, like all drugs entering the aqueous humor, is hydrolyzed during passage through the cornea. Maximum aqueous humor concentration (about 15-30 ng/ml) is reached approximately 2 hours after topical application of latanoprost as monotherapy. It is distributed mainly in the anterior segment of the eye, conjunctiva and eyelids.
The plasma clearance of latanoprost acid is 0.4 l/h/kg; the volume of distribution is small, 0.16 l/kg, resulting in a rapid plasma elimination half-life (17 minutes). After topical ophthalmic administration, the systemic bioavailability of latanoprost is 45%. Latanoprost acid is 87% bound to plasma proteins.
Latanoprost acid metabolism in the eye is practically absent. The main metabolism occurs in the liver. The main metabolites (1,2-dinor and 1,2,3,4-tetranor) have no or only weak biological activity and are excreted mainly in the urine.
Timolol. The maximum concentration of timolol in the aqueous humor is reached approximately 1 hour after topical application of eye drops. Part of the dose is absorbed systemically; the maximum plasma concentration is 1 ng/ml and is reached 10-20 minutes after topical application of one drop in each eye once daily (300 mcg/day). The half-life of timolol from blood plasma is approximately 6 hours. Timolol is extensively metabolized in the liver. Metabolites are excreted in the urine as unchanged timolol.
Lanotan® T. No pharmacological interactions were observed between latanoprost and timolol, despite an increase in the concentration of latanoprost acid in the aqueous humor by almost 2 times after the use of the combined drug compared to monotherapy.
Indication
Reduction of intraocular pressure in patients with open-angle glaucoma and elevated intraocular pressure with insufficient response to treatment with beta-blockers or topical prostaglandin analogues.
Contraindication
- Hypersensitivity to the active substance or to any other component of the drug;
- reactive respiratory tract diseases, including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease;
- sinus bradycardia; sick sinus syndrome; sino-auricular block; atrioventricular block of the 2nd or 3rd degree, not controllable with a pacemaker; heart failure; cardiogenic shock;
- pregnancy and breastfeeding.
Interaction with other medicinal products and other types of interactions
Special studies of the interaction of Lanotan® T with other drugs have not been conducted.
Paradoxical increases in intraocular pressure have been reported following concomitant use of two prostaglandin analogues. Therefore, the use of two or more prostaglandins, prostaglandin analogues or prostaglandin derivatives is not recommended.
There is a possibility of an additive effect leading to the development of arterial hypotension and/or pronounced bradycardia when beta-blockers in the form of eye drops are prescribed simultaneously with oral calcium channel blockers, beta-adrenergic blockers, antiarrhythmic drugs (including amiodarone), digitalis glycosides, parasympathomimetics, guanethidine.
Increased systemic beta-blockade (e.g. decreased heart rate, depression) has been observed during the combined use of CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol.
The effect on intraocular pressure or the known effects of systemic beta-blockade may be enhanced when Lanotan® T is administered concomitantly to patients already receiving oral beta-blockers. The use of two or more topical beta-blockers is not recommended.
In isolated cases, mydriasis has been reported following the concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine).
The use of beta-blockers may lead to increased hypertension in response to abrupt withdrawal of clonidine.
Beta-blockers may enhance the hypoglycemic effect of antidiabetic drugs. Beta-blockers may mask the symptoms of hypoglycemia.
Application features
Systemic effects.
Like other topical ophthalmic drugs, Lanotan® T is absorbed systemically. Since the drug contains the beta-adrenergic agent timolol, the same types of adverse reactions from the pulmonary, cardiovascular and other systems may occur as with the use of systemic beta-adrenergic receptor blockers. The frequency of systemic adverse reactions after topical use is lower than after systemic administration of the drug. Measures to reduce systemic absorption are given in the section "Method of administration and dosage".
Heart disorders.
The need for beta-blocker treatment in patients with cardiovascular disease (e.g. coronary artery disease, Prinzmetal's angina, and heart failure) and hypotension should be carefully evaluated and alternative treatment options should be considered. Patients with cardiovascular disease should be monitored for signs of worsening of these conditions and for adverse reactions.
Because beta-blockers prolong excitation time, they should be administered with caution to patients with first-degree heart block.
Cases of cardiovascular reactions and, in isolated cases, fatal outcome from heart failure have been described following the administration of timolol.
Vascular disorders
The drug should be used with caution in patients with severe peripheral circulatory disorders (i.e., patients with severe forms of Raynaud's disease or Raynaud's syndrome).
Respiratory system disorders.
Respiratory reactions, including fatal cases of bronchospasm in patients with asthma, have been reported with some ophthalmic beta-blockers. Lanotan® T should be used with caution in patients with mild to moderate chronic obstructive pulmonary disease (COPD) and should only be prescribed if the potential benefit outweighs the potential risk.
Hypoglycemia/diabetes
Beta-blockers should be prescribed with caution to patients who may develop spontaneous hypoglycemia or to patients with unstable diabetes mellitus, since beta-blockers may mask the symptoms of hypoglycemia.
Beta-blockers can also mask the signs of hyperthyroidism.
Corneal diseases
Ophthalmic beta-blocker medications can cause dry eyes, so patients with corneal disease should be prescribed these medications with caution.
The effect on intraocular pressure or the known effects of systemic beta-blockade may be potentiated by concomitant use of timolol in patients already receiving systemic beta-blockers. Such patients should be closely monitored. The use of two topical beta-blockers is not recommended (see section 4.5).
Anaphylactic reactions
When using beta-blockers, patients with a history of atopic diseases or severe anaphylactic reactions to various allergens may react more intensely to repeated exposure to these allergens and may not respond to the usual doses of adrenaline used to treat anaphylactic reactions.
Detachment of the choroid of the eye
Cases of choroid detachment have been described during treatment aimed at suppressing the formation of intraocular fluid (e.g., with the use of timolol, acetazolamide) after trabeculectomy.
Surgical anesthesia
Ophthalmic beta-blockers may block the systemic effects of beta-adrenergic agonists, such as adrenaline. If the patient is taking timolol, the anesthesiologist should be informed.
Concomitant therapy
Timolol may interact with other drugs (see section “Interaction with other drugs and other types of interactions”).
The use of two topical beta-blockers or two topical prostaglandins is not recommended.
Effects on the organs of vision
Latanoprost may gradually increase the amount of brown pigment in the iris and thus change the eye colour. As with latanoprost eye drops, increased pigmentation was observed in 16-20% of all patients treated with the combination product for 1 year (based on photographs). This effect is mainly observed in patients with mixed iris colour, e.g. green-brown, yellow-brown or blue/green-brown, and is due to increased melanin content in the stromal melanocytes of the iris. Typically, the brown pigmentation around the pupil of the affected eye spreads concentrically towards the periphery, but the whole iris or part of it may be stained more intensely brown. In patients with uniform blue, green, grey or brown eyes, such changes were rarely observed during latanoprost treatment for 2 years in clinical studies.
The change in iris color occurs slowly and may go unnoticed for months or years. This change is not associated with any symptoms or the development of pathological changes.
No further increase in brown iris coloration was observed after discontinuation of treatment, but the color changes that occurred may be permanent.
Darkening of the eyelid skin, which may be reversible, has been reported in association with the use of latanoprost.
Latanoprost may gradually change the eyelashes and vellus hair around the treated eye. These changes include an increase in the length, thickness, pigmentation, and number of eyelashes or hair, and eyelashes growing in the wrong direction. The changes in eyelashes are reversible after stopping treatment.
The treatment does not affect nevi or freckles of the iris.
Pigment accumulation in the trabecular meshwork or elsewhere in the anterior chamber has not been observed, but patients should be monitored regularly. Depending on the clinical picture, treatment may be discontinued if increased iris pigmentation is observed.
Before prescribing treatment, the patient should be informed about the possibility of developing eye color changes. Permanent heterochromia may occur when treating one eye.
There is no confirmed experience with latanoprost in inflammatory, neovascular, chronic angle-closure or congenital glaucoma, in open-angle glaucoma in patients with artephakia and in pigmentary glaucoma. Latanoprost has no or negligible effect on the pupil, but there is no confirmed experience with acute angle-closure glaucoma. Therefore, until sufficient experience is available, it is recommended to prescribe latanoprost with caution in these conditions.
Latanoprost should be used with caution in patients with a history of herpetic keratitis and avoided in cases of active keratitis caused by herpes simplex virus and in patients with a history of recurrent herpetic keratitis associated with the use of prostaglandin analogues.
Macular edema, including cystoid macular edema, has been reported with latanoprost. These cases have been reported mainly in aphakic patients, in patients with artephakia and posterior capsule detachment, or in patients with known risk factors for macular edema. Lanotan® T should be used with caution in such patients.
Using contact lenses
Lanotan® T contains benzalkonium chloride, which is often used as a preservative in ophthalmic preparations. Benzalkonium chloride has been reported to cause punctate keratitis and/or toxic ulcerative keratopathy, may cause eye irritation, and is known to discolour soft contact lenses. Careful observation is required in patients with dry eye or corneal conditions who use Lanotan® T frequently or for long periods. Contact lenses may absorb benzalkonium chloride, so lenses should be removed before instillation of Lanotan® T; they may be reinserted after 15 minutes (see section “Dosage and Administration”).
Timolol maleate has been reported to occasionally exacerbate muscle weakness in some patients with myasthenia gravis or myasthenic symptoms (such as diplopia, ptosis, general weakness).
Use during pregnancy or breastfeeding
Pregnancy
In animal studies, latanoprost or timolol did not appear to have any effect on male or female reproductive function.
Latanoprost
There are no adequate data from the use of latanoprost in pregnant women. Animal studies have shown reproductive toxicity. The potential risk for humans is unknown.
Timolol
There are no adequate data on the use of timolol in pregnant women. Timolol should not be used during pregnancy unless clearly necessary.
For ways to reduce systemic absorption, see the section "Method of administration and dosage".
Epidemiological studies have not revealed any malformative effects, but it has been shown that there is a risk of intrauterine growth retardation with internal use of beta-blockers. In addition, signs and symptoms of beta-adrenergic blockade (including bradycardia, hypotension, respiratory distress and hypoglycemia) have been observed in newborns whose mothers took beta-blockers during pregnancy. If Lanotan® T is used in pregnant women in the third trimester of pregnancy, the condition of the newborn should be carefully monitored during the first days of life.
Therefore, Lanotan® T should not be used during pregnancy.
Breastfeeding period
Timolol maleate has been detected in human breast milk after oral and ocular administration. Beta-blockers are excreted in human milk. However, therapeutic doses of timolol in eye drops are not sufficient for the amount excreted in breast milk to cause clinical symptoms of beta-blockade in the newborn. For ways to reduce systemic absorption, see section "
Method of administration and doses.
Latanoprost and its metabolites may pass into breast milk, therefore Lanotan® T should not be used in breastfeeding women.
Ability to influence reaction speed when driving vehicles or other mechanisms
Instillation of eye drops may cause short-term visual impairment. Until vision returns to normal, you should not drive or operate other machinery.
Method of administration and doses
Adults, including elderly patients.
The recommended dose is 1 drop in the affected eye(s) once daily.
If a dose is missed, treatment should be continued with the next scheduled dose. The dose should not exceed 1 drop in the affected eye(s) once daily.
Contact lenses must be removed before instilling eye drops. Lenses can be put back in only 15 minutes after instilling the drops.
If a patient is prescribed more than one ophthalmic medication, the medications should be administered at least 5 minutes apart.
When the patient uses nasolacrimal occlusion or if the patient closes the eyelids for 2 minutes, systemic absorption of the drug is reduced. This may lead to a decrease in the intensity of systemic side effects and an increase in the effectiveness of the local action of the drug.
Children
The safety and efficacy of Lanotan® T in children and adolescents have not been established.
Overdose
There are no data on overdose of latanoprost with timolol in humans.
Symptoms of systemic overdose of timolol: bradycardia, hypotension, bronchospasm, cardiac arrest. If such symptoms occur, symptomatic and supportive therapy should be administered. Studies have shown that timolol is not completely removed by dialysis.
The following information may be useful if latanoprost is accidentally ingested. Treatment. If necessary, perform gastric lavage. Symptomatic treatment. Latanoprost is extensively metabolized during the first pass through the liver. When intravenously infused at a dose of 3 μg/kg in healthy volunteers, no symptoms occurred, but the use of doses of 5.5-10 μg/kg was accompanied by nausea, abdominal pain, dizziness, fatigue, flushing and increased sweating. These manifestations were mild to moderate in severity and disappeared without treatment within 4 hours after the end of the infusion. In patients with moderate bronchial asthma, bronchoconstriction was not induced by latanoprost when applied topically to the eyes at a dose of seven times the clinical dose of latanoprost.
There have been reports of inadvertent overdose with timolol maleate solution resulting in systemic effects similar to those seen with systemic beta-adrenergic agents, such as dizziness, headache, dyspnea, bradycardia, bronchospasm, and cardiac arrest.
Adverse reactions
With latanoprost, most of the side effects are visual. Patients experience increased pigmentation of the iris, which may be permanent. Other side effects from the visual system are usually short-lived and dose-dependent. With timolol, the most serious side effects are systemic, including bradycardia, arrhythmia, congestive heart failure, bronchospasm, and allergic reactions.
Like other topical ophthalmic drugs, timolol is absorbed into the systemic circulation. This may lead to systemic adverse reactions similar to those seen with systemic beta-blockers. The incidence of systemic adverse reactions following topical ophthalmic drugs is lower than with systemic administration. The adverse reactions listed are consistent with those reported with ophthalmic beta-blockers.
From the nervous system: headache.
On the part of the organs of vision: increased pigmentation of the iris, eye irritation (including burning, inflammation and itching), eye pain, eye redness, conjunctivitis, blurred vision, increased lacrimation, blepharitis, corneal disorders, conjunctival disorders, false refraction.
Skin and subcutaneous tissue disorders: skin rash, itching, hypertrichosis.
From the vascular system: hypertension.
Infections and infestations: infections, sinusitis and upper respiratory tract infections.
Musculoskeletal and connective tissue disorders: arthritis.
Certain side effects specific to individual components of Lanotan® T.
For latanoprost.
Infections and infestations: herpetic keratitis.
Nervous system: dizziness.
On the part of the organs of vision: changes in the eyelids and vellus hair (increased length, thickness, number and increased pigmentation); macular epithelial erosion; periorbital edema; iritis/uveitis; macular edema (in patients with aphakia, in patients with artephakia and posterior lens capsule detachment or in patients with known risk factors for macular edema); dry eye mucosa; keratitis, corneal edema and erosion; incorrect direction of eyelashes, which can lead to eye irritation, iris cysts; photophobia; periorbital and eyelid changes as a result of deepening of the palpebral sulcus, foreign body sensation, sand in the eye.
Cardiovascular system: worsening of angina pectoris, palpitations.
Respiratory, mediastinal and thoracic disorders: asthma, asthma exacerbation, dyspnoea.
Skin and subcutaneous tissue disorders: darkening of the eyelid skin and localized skin reaction on the eyelids.
Musculoskeletal and connective tissue disorders: joint pain, muscle pain.
General disorders: chest pain.
For timolol.
On the part of the immune system: systemic allergic reactions, including angioedema, urticaria, localized and generalized rashes, itching, anaphylactic reaction.
Metabolic and digestive disorders: hypoglycemia, anorexia.
On the part of the psyche: depression, memory impairment, insomnia, nightmares, confusion, hallucinations, anxiety, disorientation, nervousness, decreased libido.
From the nervous system: fainting, cerebral circulation disorders, cerebral ischemia, increased symptoms of myasthenia gravis, dizziness, paresthesia, drowsiness, headache.
On the part of the organs of vision: symptoms of eye irritation (burning sensation, stinging in the eyes, itching, tearing, redness), blepharitis, keratitis, blurred vision, as well as detachment of the choroid of the eyes after trabeculectomy
(see section "Features of application"),
decreased corneal sensitivity, dry eyes, corneal erosion, ptosis, refractive changes, diplopia, conjunctival hyperemia, transient punctate epithelial erosions, eyelid edema, distichiasis.
On the part of the auditory system: tinnitus.
Cardiovascular system: bradycardia, chest pain, palpitations, edema, arrhythmia, congestive heart failure, atrioventricular block, cardiac arrest, heart failure, worsening of angina.
Respiratory, mediastinal and thoracic disorders: bronchospasm (predominantly in patients with pre-existing bronchospastic disease), shortness of breath, cough, pulmonary edema, respiratory distress.
Gastrointestinal: dysgeusia, nausea, dyspepsia, diarrhea, dry mouth, abdominal pain, vomiting, retroperitoneal fibrosis.
Skin and subcutaneous tissue disorders: alopecia, psoriatic eruptions or exacerbation of psoriasis, skin eruptions, pseudopemphigoid.
Musculoskeletal and connective tissue disorders: myalgia, systemic lupus erythematosus.
From the reproductive system and mammary glands: sexual dysfunction, decreased libido, impotence, Peyronie's disease.
General disorders and administration-related disorders: asthenia/fatigue, chest pain, edema.
Isolated cases of corneal calcification have been reported with the use of phosphate-containing eye drops in some patients with significant corneal damage.
Expiration date
2 years.
Shelf life after opening the bottle is 28 days at a temperature not exceeding 25 °C.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in a place protected from light at a temperature of 2 to 8 °C.
Keep out of reach of children.
Packaging
2.5 ml per bottle. 1 bottle per pack.
Vacation category
According to the recipe.
Producer
PJSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Frunze St., 74.
