КСАЛАКОМ

Active material: Latanoprost, Timolol
When ATH: S01ED51
CCF: Antiglaucoma drug
ICD-10 codes (testimony): H40.0, H40.1
When CSF: 26.01.01.09
Manufacturer: PFIZER MFG. BELGIUM N.V. (Belgium)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Eye drops as a clear, colorless solution.

Excipients: benzalkonium chloride (as 50% solution), sodium hydrogen phosphate, anhydrous, sodium dïgïdrofosfata monohydrate, sodium chloride, water d / and (if necessary (to ensure pH) Add a solution of hydrochloric acid 10% or a solution of sodium hydroxide 10% – q.s.).

2.5 ml – dropper bottle plastic (1) – packs cardboard.

Pharmacological action

Protivoglaucomny combined product. Mechanism of lower elevated IOP y latanoprosta and timolola varies, that provides an additional reduction of IOP compared with the effect of the application of each of these components as monotherapy.

Latanoprost – analogue of prostaglandin F_2a – is a selective agonist prostanoida FP and lowers IOP intraocular pressure by increasing the outflow of aqueous humor, mainly, by uveoskleral'nym, as well as through the trabecular network. Latanoprost has no significant effect on products watery moisture and does not affect blood-ophthalmic barrier.

For short-term treatment of latanoprost is not causing seepage fljuorescina in rear segment of the eye psevdofakii. When used in therapeutic doses has no significant pharmacological effects on the cardiovascular and respiratory systems.

Timolol – selective beta₁– and beta₂-adrenoblokator. Does not have significant internal sympathomimetic activity, depression has no direct action on myocardium, has no membranostabilizirujushhej and mestnoanestezirujushhej activity.

Β-adrenoceptor blockade causes decreased cardiac output in healthy subjects and patients with heart diseases. In patients with severe myocardial dysfunction beta-adrenoblokatora may inhibit the stimulating effect of the sympathetic nervous system, necessary for adequate work of heart.

Β-adrenoceptor blockade in the bronchi and bronhiolah leads to increased airway resistance under the influence of the parasympathetic nervous system. A similar effect can be dangerous for patients with bronchial asthma and other bronhospasticheskimi diseases.

Application of timolola maleate in the form of eye drops is elevated and normal IOP irrespective of the presence or absence of glaucoma. Elevated IOP is the main risk factor for glaucoma vision field loss. The higher the IOP, the higher the probability of loss of glaucoma fields of view and optic nerve damage.

The exact mechanism of reduction of IOP under the influence of timolola maleate is not installed. The results of tonografii and fljuorometrii demonstrate that, that the main mechanism of action can be associated with the reduction of aqueous humor formation. But, Some studies have also observed and a slight increase in the outflow of aqueous humor.

The product "Csalacom"^® occurs within the first hour after applying, maximum effect within 6-8 no. Repeated application of adequate IOP reduction maintained for 24 hours after injection.

Pharmacokinetics

Not applicable farmakokineticheskeogo interactions between latanoprost and timolol maleate, although after 1-4 hours after application Ksalakoma^® latanoprost acid concentration in the aqueous humor was about 2 times higher, than with monotherapy.

Latanoprost

Absorption

Latanoprost, It is prodrug, easily penetrates through the cornea, wherein it hydrolyzes to form a biologically active (acid). C_max in the aqueous humor is reached through 2 h after topical application of.

Distribution

V_d is 0.16 ± 0.02 l/kg.. Acid latanoprosta is defined in the watery moisture during the first 4 no, and in plasma – only during the first hour after topical application.

Metabolism

Latanoprost undergoes hydrolysis in the cornea of the eye, under the influence of esterases with formation of the biologically active acid. Acid latanoprosta, coming into the bloodstream, metabolised, primarily, in the liver by Beta oxidation of fatty acids with the formation of 1.2-dinor- and 1, 2, 3, 4--tetranor metabolites.

Deduction

Acid latanoprosta quickly eliminated from the blood plasma T_1/2 is 17 m. Systemic clearance is approximately 7 ml / min / kg. Metabolites are, primarily, kidney: after topical application with a urine output of about 88% dose.

Timolola maleate

C_max timolola maleate in watery moisture is achieved through 1 no. Of the dose exposed system and absorption through 10-20 minutes after topical application of drug 1 drop. in each eye 1 time / day (300 mg / day) in plasma achieved C_max , component 1 ng / ml.

T_1/2 timolola maleate from plasma is about 6 no. Timolola maleate actively metabolised in the liver. Metaʙolitы, as well as a number of unmodified timolola maleate, the kidneys.

Testimony

— to reduce elevated intraocular pressure in patients with open-angle glaucoma and high oftal'motonusom with the ineffectiveness of other IOP lowering medication for topical application.

Dosage regimen

Adults (including elderly patients) – by 1 drop into the affected eye(and) 1 time / day.

Side effect

In applying the drug "Csalacom"^® following unwanted reactions with frequency ≥ 1%.

On the part of the organ of vision: blurred vision, .Aloe, Cataract, conjunctivitis, lesion of conjunctiva (incl. follicles, papillary reaction of conjunctiva, pinpoint hemorrhages), corneal lesions (incl. erosion, pigmentation, punctate keratitis), refractive error, hyperemia eyes, eye irritation, sore eyes, increased pigmentation of the iris, keratit, photophobia, the fields of vision loss.

The respiratory system: sinusitis, infections of the upper respiratory tract.

Metabolism and nutrition: diabetes, hypercholesterolemia.

Mental disorders: depression.

From the nervous system: headache.

Cardio-vascular system: arterial hypertension.

Dermatological reactions: hypertryhoz, rash, skin irritation, dermatohalazion.

On the part of the musculoskeletal system: arthritis.

Other: infection.

Adverse reactions, observed when alone latanoprostom

On the part of the organ of vision: eye irritation (burning sensation, feeling of sand in the eyes, itch, tingling and foreign body sensation), blurred vision; fleeting black spot erosion of epithelium, swelling of the eyelids and corneal erosion; Irit, uveitis; macular edema (incl. cystoid); elongation, thickening, the upsurge and increased pigmentation of the eyelashes and downy hair, changing the direction of Eyelash growth, sometimes causes irritation of the eyes.

Dermatological reactions: skin rash, darkening of the eyelid skin, local skin reactions on the eyelids.

From the nervous system: dizziness.

The respiratory system: bronchial asthma (incl. acute attacks or exacerbations of the disease in patients with bronchial asthma in history), breathlessness.

On the part of the musculoskeletal system: artralgii, mialgii.

Other: non-specific chest pain.

Adverse reactions, observed when alone timolola maleatom (in the form of eye drops)

On the part of the organ of vision: cystoid makuliarny edema, reduced corneal sensitivity; choroidal detachment after filtration surgery; ptosis, visual impairment (incl. changing the refraction, diplopia).

Allergic reactions: systemic allergic reactions (incl. anaphylaxis, angioedema, hives, localized and generalized rash).

Metabolism and nutrition: anorexia, hidden symptoms of hypoglycemia in patients with diabetes mellitus.

Mental disorders: behavior changes, confusion, hallucinations, alarm, disorientation, nervousness, memory loss, insomnia, nightmares, decreased libido.

From the nervous system: golovnogo ischemia mozga, acute stroke, dizziness, increased symptoms of myasthenia gravis, paresthesia, drowsiness, fainting.

On the part of the organ of vision: cystoid makuliarny edema, reduced corneal sensitivity, choroidal detachment after filtration surgery, ptosis, visual impairment, incl. changing the refraction and diplopia.

On the part of the organ of hearing: noise in ears.

From the digestive system: diarrhea, dry mouth, dyspepsia, nausea, ryetropyeritonyealinyi fibrosis.

Cardio-vascular system: arrhythmia, bradycardia, cardiac arrest, heart failure, heart block, heartbeat, progression of angina; intermittent claudication, cold extremities, hypotension, Raynaud's syndrome.

The respiratory system: bronchospasm (primarily, in patients with previous bronhospasticheskim disease), cough, breathlessness, nasal congestion, pulmonary edema, respiratory insufficiency.

Musculoskeletal system and connective tissue: SLE.

Reproductive system: impotence, Peyronie's disease.

Dermatological reactions: alopecia, psevdopemfigoid, psoriazopodobnaja rash, exacerbation of psoriasis.

Other: asthenia, fatiguability, chest pain, swelling.

Contraindications

-reactive respiratory disease (incl. bronchial asthma or an indication of its history);

-COPD heavy currents;

— sinusova aetiology;

— AV-blockade II and III degrees;

-clinically expressed heart failure;

- Cardiogenic shock;

- Hypersensitivity to the drug.

FROM caution the preparation is used to treat inflammatory, neovascular, angle closure glaucoma or congenital, Open-glaucome combined with psevdofakiej, pigmentary glaucoma (due to the lack of sufficient experience with the drug); aphakia, psevdofakii with rear lens capsule, in patients with known risk factors for macular edema (When treating latanoprostom myocarditis development of macular edema, incl. cistoidnogo).

Pregnancy and lactation

Adequate controlled studies of the drug in pregnant women has been carried out.

Use of the drug during pregnancy is possible only in case, when the intended benefits to the mother outweighs the potential risk to the fetus.

Latanoprost and its metabolites in breast milk may occur; timolola maleate when applied in the form of eye drops is also found in breast milk. If necessary, use during lactation should decide the issue of termination of breastfeeding, in view of the risk of serious adverse reactions in infants, breastfed, as well as the importance of the drug to the mother.

Cautions

"Csalacom"^® should be used more often 1 times / day, because more frequent use weakens the effect of reducing the IOP.

When I miss one dose, next dose should be entered in normal times.

If the patient is simultaneously use other eye drops, they should be applied at intervals of not less than 5 m.

"Csalacom"^® contains benzalconia chloride, which can be adsorbed on contact lenses. Therefore, before dropping the contact lenses should be removed, and then install via 15 m.

Latanoprost

Latanoprost can cause a gradual increase of brown pigment in the IRIS. Changing the eye color due to increased number of melanocytes of the IRIS stromal melanin, rather than an increase in the number of melanocytes themselves. In typical cases, the brown pigmentation appears around the pupil spreads concentrically and on the periphery of the IRIS. While the entire iris or parts thereof become Brown. In most cases, the color change is insignificant and may not be clinically. Increased pigmentation of the iris of one or both eyes is observed, mainly, in patients with mixed color Iris, contains the basis for Brown. The drug has no effect on nevi and Lentigo IRIS; accumulation of pigment in the trabecular network or the anterior Chamber of the eye is not marked.

When determining the pigmentation of the IRIS for more 5 years revealed no adverse effects enhance pigmentation even with continued therapy latanoprostom. In patients of IOP reduction was the same regardless of the degree of pigmentation of the IRIS. Hence, latanoprostom treatment can be continued and in cases of enhancing pigmentation of the IRIS, but patients should be under regular supervision and, depending on the clinical situation, treatment can be discontinued.

Increased pigmentation of the IRIS is usually observed during the first year after the start of treatment, rarely – After the second or third year. After the fourth year of treatment, this effect was not observed. The rate of progression of pigmentation over time is reduced and stabilized within 5 years. In the more remote periods of increased IRIS pigmentation effects have not been studied. After the end of treatment reinforce brown pigmentation of the IRIS is not mentioned, However, changing the eye color may be irreversible.

In connection with the application of latanoprosta cases of eyelid skin darkening, which may be reversible.

Latanoprost can cause gradual changes of eyelashes and downy hair, such as elongation, thickening, increased pigmentation, an increase in density and changing the direction of Eyelash growth. Eyelash changes are reversible and disappear after discontinuation of treatment.

Patients, applying drops to treat only one eye, the development of heterochromia.

Timolola maleate

The local application of beta blockers could experience the same unwanted reactions, as the systems use.

Patients with severe heart disease in history should be monitored with a view to the timely detection of symptoms of congestive heart failure. The local application of timolola maleate may experience the progression of strokes prinzmetala, peripheral and Central circulatory disorders, hypotension, bradycardia, heart failure fatal, severe reactions on the part of the respiratory system (incl. fatal bronchospasm in patients with bronchial asthma).

Before the extensive surgery should discuss the feasibility of phasing out beta-adrenoblokatorov. Drugs in this group violate the ability of the heart to the reflex response to Beta Adrenergic stimulation, that can increase the risk of anaesthesia. Cases of prolonged severe arterial hypotension during anesthesia and difficulties in restoring and maintaining cardiac activity. During the operation the effects of beta blockers can be eliminated by sufficient doses of adrenoreceptor agonists.

Beta-adrenoblokatora may strengthen gipoglikemicescoe effect oral gipoglikemicakih funds and mask the symptoms of hypoglycemia. They should be used with caution in patients with spontaneous hypoglycemia or diabetes (particularly labile currents), receiving insulin or oral gipoglikemicakie means.

Therapy with beta-adrenoblokatorami may mask the symptoms of hyperthyroidism, abrupt discontinuation of treatment may exacerbate the disease.

In the treatment of beta-adrenobloktorami in patients with atopiej or heavy anafilakticheskimi reactions to allergens in history may increase response to repeated contact with the allergen. While epinephrine (adrenaline) at conventional doses, used for anaphylactic reactions, may be ineffective.

In rare cases, timolola maleate causes increased muscle weakness in patients with myasthenia gravis or miastenicheskimi symptoms (eg, diplopia, Ptosis, generalized weakness).

In the application of funds, lowering intraocular pressure, Describes the choroid detachment after filtration procedures.

Use in Pediatrics

Safety and efficacy of Ksalakoma^® the children are not installed.

Impact on the ability to manage vehicles and working with machinery

Use eye drops can cause transient blurring. While this effect does not disappear, patients should not drive or use complex equipment.

Overdose

Latanoprost

Symptoms: eye irritation, conjunctival hyperemia. In addition to eye irritation and redness kongyunctiv other unwanted changes on the part of the organ of vision in overdose are not known latanoprosta.

In the event of accidental ingestion should be considered latanoprosta, what 1 bottle with 2.5 ml solution contains 125 mcg latanoprosta. More 90% the drug is metabolized in “first pass” through the liver.

In/in cefuroxim dose 3 µg/kg in healthy volunteers did not caused any symptoms, However, when administered in a dose of 5.5-10 µg/kg experienced nausea, abdominal pain, dizziness, fatiguability, hot flashes and sweating.

In patients with bronchial asthma moderately introduction latanoprosta dose, in 7 times higher than the therapeutic causing bronchospasm.

Timolola maleate

Symptoms: dizziness, headache, breathlessness, bradycardia, bronchospasm, cardiac arrest (similar to symptoms, persistent systems use of beta blockers). These symptoms have been observed in cases of unintentional overdose of eye drops timolola maleate.

The in vitro study, it was shown, that in dialysis timolola maleate easily eliminated from plasma or whole blood. In patients with renal insufficiency timolola maleate dializirovalsja worse.

Treatment: Ksalakoma overdose^® symptomatic therapy.

Drug Interactions

Special studies the interactions of drugs with the drug "Csalacom"^® not carried out.

Not recommended Simultaneous with Ksalakomom^® use inside other beta-adrenoblokatorov, Since may decrease or increase of IOP expressed systemic effects beta-adrenoblokatorov.

While zacapawanyi in the eyes of the two analogues of prostaglandins describes a paradoxical increase in IOP, Therefore, the simultaneous use of two or more prostaglandins, their analogs or derivatives is not recommended.

While applying timolola maleate with epinephrine (adrenaline) sometimes developed Mydriasis.

Possible with the development of additivoe effect systemic arterial hypotension and/or bradycardia with a combination of timolola maleate with: Calcium channel blockers, funds, causing a reduction in the level of Catecholamines, beta-blockers, antaritmicheskie tools, cardiac glycosides.

Beta-adrenoblokatora may strengthen gipoglikemicescoe effect protivodiabeticakih funds.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C. Shelf life – 2 year.

Opened vials should be stored at a temperature of no higher than 25° c and used within 4 weeks.