Tapticom drops 0.0015% + 0.5% 0.3ml #30

Tapticom instruction for use

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Composition

    1 ml of eye drops contains 0.015 mg of tafluprost and 5 mg of timolol, which corresponds to 6.84 mg of timolol maleate;
    auxiliary substances: glycerin sodium phosphate, dodecahydrate; Trilon B, polysorbate 80, sodium hydroxide and / or concentrated hydrochloric acid, water for injection.

pharmachologic effect

Pharmacodynamics.

mechanism of action
Tapticom is a combined preparation containing two active substances - tafluprost and timolol. These two active substances reduce intraocular pressure (IOP) by additional mechanisms of action, as well as a joint action resulting in an additional volume of BOT using only one of the two substances.
Tafluprost is a fluorinated analogue of prostaglandin F 2? , Tafluprostova acid, biologically active metabolite tafluprostu, is a highly active selective antagonist of the human prostate FP receptor.
Pharmacodynamic studies in animals show that tafluprost reduces intraocular pressure, increasing the percutaneous outflow of eye fluid.
Timolol maleate is a non-selective beta-adrenergic receptor. The exact mechanism of action of timolol maleate in relation to intrauterine disease, but studies on fluorescein and research by the method of tonography, which can be associated with reduced fluid formation. However, in some studies, there was also a slight increase in efflux activation.
clinical efficacy
In the 6-month study (n = 400) of patients with open-angle glaucoma or ophthalmic hypertension and an average untreated WTO from 24 to 26 mm Hg. the effect of reducing IOP by Tapticom (once a day in the morning) was compared with a joint intake of 0.0015% tafluprost (once a day in the morning) and 0.5% timolol (twice a day). Tapticom ® was no less effective (than the 0.0015% tafluprost and 0.5% timolol), which was used together. The average daily decline in the WTO relative to the initial values ​​was 8 mm Hg. Art. in both groups with a primary endpoint of 6 months (
ranged from 7 to 9 mm Hg. Art. in both groups at different times during the day during study visits).
In another six-month study (n = 564), Tapticom was compared to a monotherapy with open official glaucoma or ophthalmic hypertension and an average untreated WTO from 26 to 27 mm Hg. Art. Patients who are not adequately controlled by 0.0015% tafluprost (WCO 20 mm Hg or more in treatment) or 0.5% timolol (22 mm Hg Hg or more in treatment) were randomized to treat TAPTICOM ® or such same monotherapy. The average daily decrease in the WTO with the use of TAPTICOM ® was statistically exceeded by the average daily decrease in WTO with the reception of tafluprost, which patients receive once a day in the morning, or when they take timolol twice a day, at visits for 6 weeks, for 3 months (primary end point of effectiveness evaluation) and for 6 months. The average daily decrease in WTO from the initial values ​​when taking Tapticom ® was 9 mm Hg. Art. compared with 7 mm Hg. st, which was observed with the reception of both monotherapies. The decrease in WTO with the use of TAPTICOM ® at different times during the day ranged from 8 to 9 mm Hg. Art. in the comparison group, the use of tafluprost monotherapy, and 7 to 9 mm Hg. Art. in the comparison group, the use of timolol as a monotherapy.
Consolidated data from patients who took Tapticom, and had a high initial WTO of 26 mm Hg. Art. (mean daily) or higher in two basic studies (n = 168), showed that the average daily decrease in the WTO was 10 mm Hg. Art. in the primary endpoint (3 or 6 months), ranging from 9 to 12 mm Hg. Art. at different times during the day.

pharmacokinetic properties

absorption
Concentrations of blood plasma and tamolol and timolol were studied in healthy volunteers after a single and repeated use of Tapticom for eight days (once a day), 0.0015% tafluprost (once daily) and 0.5% timolol (two The concentration of blood plasma tafluprostovoy reached a maximum value 10 minutes after dosing and decreased below the lower limit of detection (10 pg / ml) 30 minutes after taking the drug TAPTICOM ®. The accumulation of tuflu-prostoic acid was insignificant, and the average concentration of tuflu-prostoic acid in the urine (mean AUC 0-last) (monotherapy: 4.45 + 2.57 pg • h / ml Tapticom ®: 3.60 + 3.70 pg • h / ml ) and the mean maximum concentration (max) (monotherapy: 23.9 +11.8 pg / ml Tapticom ®: 18.7 + 11.9 pg / ml) were slightly lower when treated with Tapticom ® compared to tafluprost alone 8. The concentration of timolol in the blood plasma reached its maximum value at the median T max (median time to reach the maximum drug concentration) of 15 and 37.5 minutes after receiving Tapticom ® drug on days 1 and 8, respectively. On day 8, the mean concentration of timolol in the urine (mean AUC 0-last) (monotherapy 5750 + 2440 pg • h / ml Tapticom ® 4560 + 2980 pg • h / ml) and the average maximum concentration (max) (monotherapy: 1100 + 550 pg / ml TAPTICOM ® 840 + 520 pg / ml) were somewhat lower when treated with Tapticom ® as compared to timolol monotherapy. The low content of timolol in blood plasma when treated with Tapticom ® is probably associated with the administration of a dose of Tapticom ® once a day as compared with the administration of a dose of timolol as a monotherapy twice a day.
Tafluprost and timolol are absorbed through the cornea. In animals, after a single instillation, the penetration of tuffuprost through the cornea with the use of the Tapticom was similar to that of tafluprost as a monotherapy, while the penetration of timolol was slightly less with Tapticom ® than with timolol as monotherapy. For tafluprostovoi acid, AUC 4 h was 7.5 ng · h / ml after taking Tapticom ® and 7.7 ng h / ml after taking tafluprost as a mono drug. For timolol, AUC 4 h was 585 ng · h / ml and 737 ng · h / ml after taking Tapticom ® and timolol monotherapy, respectively. T max for tafluprostovoy acid was 60 minutes both with treatment with Tapticom ® and with the treatment of tafluprost monotherapy, whereas T max for timolol was 60 minutes with Tapticom ® and 30 min with timolol monotherapy.
distribution
Tafluprost
The animals did not have a specific distribution of radiolabeled tafluprost in the iridium-ciliary region or choroid (choroid), as well as the retinal pigment epithelium, which indicated a low affinity for the melanin pigment. In a study with general actoradiography in animals, the highest concentration of radioactivity was observed in the cornea, and only then in the eyelids, sclera, and iris. Beyond the eye radioactivity spread to lacrimal organs, the sky, esophagus and gastrointestinal tract, kidneys, liver, gall bladder and bladder. The binding of tafelprostoic acid to human serum albumin in vitro was 99% at a tuflu-prostoic acid concentration of 500 ng / ml.
timolol
In animals, the maximum level of radioactivity associated with timolol in the eye fluid was reached 30 minutes after a single instillation of timolol labeled with a radioactive isotope 3 H (0.5% solution: 20 μl / eye) in both eyes. Timolol is removed from the eye fluid much faster than from the tissues of the pigmented iris and ciliary body.
Metabolism
Tafluprost
The main metabolic pathway of tafluprost in humans that has been tested in vitro is hydrolysis to a pharmacologically active metabolite, tafluprostoic acid, which is further metabolized by glucuronization or beta oxidation. Beta-oxidation products 1,2-dinor and 1,2,3,4-tetranor tafluprostovoy acid, pharmacologically inactive, may be subject to glucuronization or hydroxylation. The enzymatic system of cytochrome P450 (CYP) is not involved in the metabolism of tafeluprost acid. According to the results of the study of the corneal tissue of animals with purified enzymes, the main esterase, responsible for ester hydrolysis to tafluprostovoy acid, is carboxyl esterase. Butylcholinesterase, but not acetylcholinesterase, can also promote hydrolysis.
timolol
Timolol is metabolized in the liver, mainly by the enzyme CYP2D6 to inactive metabolites, which are excreted primarily by the kidneys.
Excretion
Tafluprost
After instilling tafluprost, labeled with radioactive isotope 3 N (0.005% ophthalmic solution, 5 μl / eye), once a day for 21 days in both eyes in animals, approximately 87% of the total radioactive dose was excreted from the body. The total amount that was excreted in the urine was approximately 27-38% of the dose and approximately 44-58% of the dose was excreted with feces.
timolol
The established half-life from plasma is about 4:00. Timolol is actively metabolized in the liver, metabolites are excreted from the body with urine along with 20% in unchanged timolol after oral administration.

Tapticom, indications for use

Decrease in intraocular pressure (IOP) in adult patients with open-angle glaucoma or ophthalmic hypertension who do not respond sufficiently to local monotherapy with beta-blockers or prostaglandin analogues and require combination therapy and which shows the use of eye drops that do not contain preservatives.

Contraindications for Tapticom

Allergic reactions to active substances or to any of the auxiliary components of the drug.
Respiratory tract irritation, as well as bronchial asthma or bronchial asthma in history, severe chronic obstructive pulmonary disease.
Sinus bradycardia, syndrome of weakness of the sinus node, as well as sinoatrial blockade, blockade of II-III degree, which is not controlled by a pacemaker, severe heart failure or cardiogenic shock.

Dosing and Administration

The recommended therapy is instillation of 1 drop of ophthalmic into the conjunctival sac of the affected eye (eye) once a day.
If a dose is missed, treatment should be continued with the next dose as planned. The dose should not exceed one drop in the affected eye (eye) 1 time per day.
Tapticom is a sterile solution that does not contain preservatives. It is intended only for single use, one tube-dropper is enough to treat both eyes. Any unused solution or its residues must be disposed of immediately.

Elderly patients

There is no need to change the dosage in elderly patients.

Renal and hepatic insufficiency

The use of eyedrops of tafluprost and timolol in patients with renal / hepatic insufficiency has been investigated, so Tapticom should be used with caution in such patients.
mode of application
ophthalmic use
To reduce the risk of darkening the skin of the eyelids, patients should wipe the excess fluid out of the skin.
With tear-nasal occlusion or closure of the eyelids within 2 minutes, systemic absorption decreases. This can result in a reduction in systemic side effects and increase in local activity.
If more than one ophthalmic preparation is prescribed, the interval between instillations of each of these drugs should be at least 5 minutes.
Contact lenses should be removed before instilling eye drops and wait at least 15 minutes, after which they can be put on again.
Patients should be advised that they avoid direct eye contact with the vial, as this can lead to eye injury.
Patients should also be informed that ophthalmic solutions, if handled improperly, may be contaminated with common bacteria that are known to cause eye infections. The use of contaminated solutions can result in severe eye damage and subsequent loss of vision.

Children.

Safety and efficacy of Tapticom for children (under the age of 18 years) are not established. Data are not available. Taptic® is not used for children.

Side effects

In clinical trials, more than 484 patients were treated with Tapticom. A frequent adverse reaction associated with the treatment reported was conjunctival / hyperemia. It occurred in approximately 7% of patients who participated in clinical trials; in most cases it was mild, and 1.2% of patients were associated with discontinuation of treatment.
Adverse reactions reported in clinical trials using Tapticom were limited to those adverse reactions reported previously with one of the active ingredients, tafluprost or timolol. No new adverse reactions, characteristic of the drug Tapticom ®, were observed in clinical trials. Most adverse reactions reported have been ocular, mild or moderate and have not been severe.
Like other topical ophthalmic drugs, tafluprost and timolol are absorbed systemically. This can cause similar adverse reactions observed when taking systemic beta-blockers. The incidence of systemic adverse reactions after topical application of ophthalmic drugs is lower than in systemic use. The following adverse reactions include those that were observed within the class of ophthalmic beta-blockers.
These adverse reactions were reported with Tapticom in clinical trials (within each of the groups listed below, the incidence of adverse reactions is presented in order of decreasing frequency).
The frequency of possible adverse reactions listed below was determined using such notations: very often (≥1 / 10); often (≥ 1/100 to

Tapticom (combination of tafluprost / timolol)

From the nervous system
Infrequently: headache
From the side of the organs of sight
Often: conjunctival / hyperemia, itching in the eyes, eye pain, eyelash changes (increase in length, thickness and number of eyelashes), discoloration of eyelashes, eye irritation, foreign body sensation in the eyes, blurred vision, photophobia (photophobia).
Infrequent: unusual sensation in the eyes, dry eyes, discomfort in the eyes, conjunctivitis, erythema eyelids, eye allergy, eyelid edema, superficial acne keratitis, increased lacrimation, inflammation of the anterior chamber of the eye, asthenopia (rapid eye fatigue), blepharitis (inflammation of the eyelids).
Additional adverse reactions that have been observed with one of the active ingredients (tafluprost or timolol) and may also occur with the use of Tapticom, listed below.
Tafluprost
From the side of the eye: Reduced visual acuity, increased pigmentation of the iris, eyelid pigmentation, conjunctival edema, discharge from the eyes, cellular reaction of the anterior chamber, cell opalescence in the anterior chamber of the eye, allergic conjunctivitis, conjunctival pigmentation, conjunctival follicles, iritis (inflammation of the iris) / uveitis (inflammation of the choroid of the eyeball).
From the skin and its derivatives: hypertrichosis century.
On the part of the respiratory system: exacerbation of bronchial asthma, dyspnea (shortness of breath / shortness of breath).
timolol
On the part of the immune system: signs and symptoms of allergic reactions, including angioedema, hives, single and multiple rashes, anaphylactic reaction, pruritus.
From the side of metabolism and nutrition: hypoglycemia.
From the side of the psyche: depression, sleep disturbance (insomnia), nightmarish dreams, memory loss, nervousness.
From the nervous system: dizziness, fainting, paresthesia, increased myasthenia gravis, hemorrhagic stroke, cerebral ischemia.
On the part of the eyes: keratitis, decreased corneal sensitivity, disturbances and visual disturbances, including refractive changes (due to cancellation of miotic means in some cases), ptosis (eyelid drooping), diplopia (double vision), choroidal detachment after filtering operation, lacrimation, erosion of the cornea.
From the organs of hearing and balance: ringing / noise in the ears.
From the heart: bradycardia, chest pain, palpitations, edema, arrhythmia, congestive heart failure, cardiac arrest, heart block, blockade, heart failure.
From the side of the vessels: hypotension, lameness, Raynaud's disease, cold limbs (hands and feet).
On the part of the respiratory system, chest and mediastinal organs: dyspnea (shortness of breath / shortness of breath), bronchospasm (especially in patients with a previous bronchospastic disease), respiratory failure, cough.
On the part of the digestive system: nausea, indigestion (indigestion), diarrhea, dry mouth, dysgeusia (flavors), abdominal pain, vomiting.
From the skin and its derivatives: alopecia (alopecia), psoriasis-like rashes or exacerbation of psoriasis, skin rash.
From the osteomuscular and connective tissue: systemic lupus erythematosus, myalgia (muscle pain), arthropathy (joint disease).
On the part of the genitals and mammary glands: Peyronie's disease (fibroplastic induction of the penis), decreased sexual desire (libido), sexual dysfunction.
General disorders and reactions at the site of administration: asthenia (general weakness) / fatigue, thirst.
Corneal calcification was reported very rarely due to the use of eye drops containing phosphate in some patients with significant corneal damage.

Drug Interactions

No special studies of interaction with other drugs have been conducted.
Possible additional effects that result in hypotension and / or severe bradycardia, when the beta-blocker ophthalmic solution is used concomitantly with oral calcium channel blockers, beta-blockers, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, guanethidine.
Oral beta-blockers can enhance the "ricochet" hypertension that arose after the withdrawal of clonidine.
An increased effect of systemic beta-blockers (eg, reduction in heart rate, depression) during combined treatment with CYP2D6 inhibitors (such as quinidine, fluoxetine, paroxetine) and timolol has been reported.
Rarely reported on mydriasis, caused by the concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine).

Overdose

Overdosing with topical application of tafluprost is unlikely to occur or be associated with toxicity.
There were reports of a random thymolol overdose, which resulted in symptoms of general poisoning similar to those observed with systemic beta-blockers, such as dizziness, headache, shortness of breath (dyspnea), bradycardia, bronchospasm, and cardiac arrest (cf. also see "Adverse Reactions").
If an overdose of Tapticom occurs, treatment should be symptomatic and supportive. Timolol is not removed by hemodialysis actively.

Storage conditions

Store at a temperature of 2 to 8 ° C (in the refrigerator) in the original packaging.
After opening the foil bag, store at a temperature of no higher than 25 ° in a dark place.
Keep out of the reach of children.

Shelf life

3 years. After opening the foil bag, store it for 28 days.
After a single use, the tube-dropper should be discarded together with the rest of the eye drops.

Terms of sell

To buy Tapticom you don't need a prescription.