Ganfort drops 0.3mg/ml + 5mg/ml 3ml

Ganfort user manual

Reed more and buy Ganfort eye drops on this page

Composition

Active substances:
bimatoprost - 0.3 mg / ml, timolol maleate - 6.8 mg / ml (in terms of timolol - 5.0 mg / ml);
Excipients:
benzalkonium chloride, citric acid monohydrate, sodium hydrogen phosphate heptahydrate, sodium chloride, hydrochloric acid, sodium hydroxide, water.

Description

A clear colorless or light yellow solution

Pharmacotherapeutic group:

antiglaucoma combined (prostaglandin P2-alpha analogue synthetic + beta-blocker)
ATX Code: S01ED51

Pharmacological properties

Pharmacodynamics

Ganfort is a combined drug, its constituent bimatoprost and timolol reduce intraocular pressure (IOP) due to the combined interaction, leading to a much more pronounced hypotensive effect compared to the effect of each of the components alone.
Bimatoprost refers to synthetic proteams, in chemical structure is similar to prostaglandin F2α (PGF2α). Bimatoprost has no effect on any of the known types of prostaglandin receptors. The hypotensive effect of bimatoprost is due to increased outflow of intraocular fluid through the trabeculae and the uveoscleral pathway of the eye.
Timolol is a non-selective beta-blocker, it does not possess internal sympathomimetic and membrane-stabilizing activity.
Timolol reduces IOP by reducing the formation of intraocular fluid. The exact mechanism of action is not established, it may be associated with inhibition of the synthesis of cyclic adenosine monophosphate (c-AMP) and is caused by endogenous stimulation of beta-adrenergic receptors.

Pharmacokinetics

Ganfort
Systemic absorption of the drug is minimal, it does not differ either with combined treatment or with instillation of each component of the drug alone. In two studies of 12 months duration, no systemic cumulation of any of the active substances was noted.
Bimatoprost
In vitro studies have shown that bimatoprost penetrates the iris and sclera. When instillating 0.03% bimatoprosta solution 1 drop in both eyes once a day for 2 weeks, the maximum concentration (Cmax) of bimatoprost in the blood plasma is reached within 10 minutes after application, and for 1.5 hours its concentration in the plasma blood is reduced to the lower limit of detection (0.025 ng / ml). The mean Cmax and the area under the concentration-time curve (AUC0-24h) of bimatoprost were close on days 7 and 14, and were 0.08 ng / ml and 0.09 ng x h / ml, respectively, indicating , that the equilibrium concentration of bimatoprost is reached during the first week of use.
Bimatoprost is moderately distributed in tissues, and the systemic volume of distribution when the equilibrium concentration of the drug is reached is 0.67 l / kg. Bimatoprost is mainly in the blood plasma. The association of bimatoprost with plasma proteins is approximately 88%. Bimatoprost is subjected to oxidation, N-deethylation and glucuronation with the formation of various metabolites.
Bimatoprost is excreted mainly by the kidneys. About 67% of the drug administered intravenously to healthy volunteers was excreted in the urine, and 25% through the gastrointestinal tract (GIT). The half-life (T1 / 2) of bimatoprost, determined after its intravenous administration, was approximately 45 minutes; and the total ground clearance is 1.5 l / h / kg.
In elderly patients:
When bimatoprost is applied 2 times a day, the mean AUC0-24 hour in elderly patients is 0.0634 ng x h / ml, which is significantly higher than the value of this parameter in healthy young people - 0.0218 ng x h / ml.
Nevertheless, this difference is not of clinical importance, since the systemic exposure of bimatoprost in its local application in elderly patients and healthy young people remains very low. Cumulation of bimatoprost in the systemic circulation is not observed, the safety profile is not different in elderly patients and young people.
Timolol
In patients who underwent surgical cataract treatment, after installation of eye drops in the form of a 0.5% solution, Cmax timolol in the intraocular fluid after 1 h was 898 ng / ml. Some of the drug enters the systemic circulation, and is metabolized in the liver. T1 / 2 timolol is about 4-6 hours. Part timolol, subjected to metabolism in the liver, is excreted through the gastrointestinal tract, and the other part and metabolites are excreted by the kidneys. Timolol binds to a small extent with the proteins of the blood plasma.

Indications for use

Decrease in intraocular pressure (IOP) in patients with open-angle glaucoma and intraocular hypertension with insufficient effectiveness of topical application of beta-adrenoblockers and prostaglandin analogues.

Contraindications

    Hypersensitivity to the components of the drug;
    Syndrome of increased reactivity of the respiratory tract, including bronchial asthma in the acute stage and previous episodes in history, severe chronic obstructive pulmonary disease (COPD);
    Sinus bradycardia, sinus node weakness syndrome, sioauralic blockade, atriovetricular blockade of II and III degree without implanted artificial pacemaker, clinically significant heart failure, cardiogenic shock.
    Age to 18 years.
Precautions for use
Dysfunction of the liver and kidneys (the drug is not sufficiently studied in this category of patients).
In patients with risk factors for edema of the macula (for example, with aphakia, and the pseudophakia rupture of the posterior capsule of the lens, as well as intraocular surgery, retinal vein occlusion, inflammatory diseases of the eyes and diabetic retinopathy).
In patients with active intraocular inflammation (eg, uveitis), as the inflammation may increase. In patients with chronic obstructive pulmonary disease (COPD) of mild and moderate degree, and only in those cases where the expected benefit exceeds the possible risk. In patients with atriovetricular blockade of the 1st degree due to the negative effect on the time of intracardiac conduction.
In patients with corneal disease, since it can induce dry eye syndrome.
In patients with diabetes mellitus (unstable flow) and impaired glucose tolerance, as the Ganfort beta-adrenoblocker timolol can mask signs of hypoglycemia.
In patients with inflammatory changes in the eyes, peovascular, inflammatory, occlusive glaucoma, congenital glaucoma or narrow-angle glaucoma (no data on efficacy and safety).

Application in pregnancy and during breastfeeding

Adequate data on the use of a fixed bimatoprost / timolol combination in pregnant women are lacking. Ganfort in pregnancy should be used only when the expected benefit to the mother exceeds the potential risk to the fetus.
Adequate and strictly controlled studies of the drug Ganfort in pregnant women were not conducted. In animal studies, data on reproductive toxicity were obtained at high doses of bimatoprost.
Epidemiological studies have not revealed congenital malformations of the fetus, but have established a risk of delaying intrauterine development of the fetus when ingesting beta-blockers. In those cases, when patients took the beta-blocker until the time of delivery, neonates had clinical symptoms characteristic of this group of drugs (eg, bradycardia, hypotension, respiratory distress syndrome and hypoglycemia). In the case of using the drug Ganfort up to delivery, it is necessary to monitor the condition of the newborn during the first days of life. In animal studies, the reproductive toxicity of timolol is indicated when doses significantly higher than those prescribed in clinical practice are used. Therefore, Ganfort is not recommended for use during pregnancy, except in cases of special need.
Beta-blockers penetrate into breast milk. However, with the use of timolol in the form of eye drops in therapeutic doses, the development of clinical symptoms in children is unlikely, in view of the lack of a sufficient amount of the drug in breast milk.
It is not known whether bimatoprost penetrates into human milk in humans, it has been found that it is contained in the milk of lactating rats. Ganfort should not be used in women during breastfeeding.

Dosing and Administration

Recommended doses in adults (including elderly patients)
One drop is buried in the conjunctival sac of the affected eye 1 time per day in the morning
If the introduction of the drug is missed once, the drug is administered the next day. Do not exceed the dose - 1 injection once a day. If you use more than 2 drugs, you need to do a 5-minute break between each installation.

Side effect

The frequency of side effects detected during the studies was evaluated as follows: very often (> 1/10), often (> 1/100, <1/10); infrequently (> 1/1000, <1/100).
In clinical studies of the drug Ganfort revealed the following side effects:
From the neutral nervous system:
often - headache, dizziness;
From the side of the organ of vision:
very often - congestion hyperemia, eyelash growth;
often - surface keratitis, corneal erosion, burning sensation, itching, burning pain in the eyes, foreign body sensation, dry eye mucosa, eyelid redness, eye pain, photophobia, discharge from the eyes, visual impairment, itchy eyelid skin, visual acuity , blepharitis, edema of the eyelids, irritation of the mucous membrane of the eyes, epiphora;
infrequently iridocyclitis, edema of the conjunctiva, tenderness of the eyelids, asthenopia, trichiasis, hyperpigmentation of the iris, deepening of the fold of the eyelid, retraction of the eyelid;
frequency unknown: cystoid macular edema.
From the respiratory system:
often - rhinitis;
infrequently - dyspnoea;
frequency unknown - bronchospasm (predominantly in patients with an existing broshpospastic disease).
From the skin and subcutaneous fat:
often, pigmentation of the skin of the eyelids, hirsutism, periocular hyperpigmentation of the skin.
Other side effects that were observed with the use of one of the components of the drug and potentially possible during the period of treatment with Ganfort:
Bimatoprost
Infectious and parasitic diseases:
infectious disease (catarrhal symptoms and symptoms of upper respiratory tract infection).
From the side of the organ of vision:
allergic conjunctivitis, cataracts, darkening of the eyelashes, blepharospasm, retinal hemorrhage, uveitis, perforbital erythema, blurred vision.
From the cardiovascular system:
increase in blood pressure.
General violations and changes in the place of introduction:
asthenia, peripheral edema.
From the gastrointestinal tract:
nausea.
Laboratory indicators:
changes in the activity of liver enzymes.
Timolol
From the immune system:
systemic allergic reactions, including Quincke's edema, hives, focal and multiple rashes, itching, anaphylaxis.
From the side of metabolism and nutrition:
hypoglycemia.
Mental disorders:
insomnia, depression, nightmarish dreams, memory loss.
From the central nervous system:
syncope, acute impairment of cerebral circulation, increased symptoms of myasthenia gravis, paresthesia, cerebral ischemia.
From the side of the organ of vision:
decrease in corneal sensitivity, diplopia, ptosis, vascular closure (after surgical treatment of glaucoma), keratitis, blurred vision.
From the organ of hearing and the vestibular apparatus:
noise in ears.
From the cardiovascular system:
atrnoventricular blockade, cardiac arrest, cardiac rhythm disturbances, loss of consciousness, bradycardia, heart failure, congestive heart failure; lowering blood pressure, chest pain, cerebral circulation, intermittent claudication, Raynaud's syndrome, cold extremities, palpitations, swelling.
From the respiratory system:
bronchospasm (mainly in individuals with episodes of bronchospasm in the anamnesis), dyspnea, cough.
From the gastrointestinal tract:
perversion of taste, nausea, diarrhea, indigestion, dryness of the oral mucosa, abdominal pain, vomiting.
From the skin and subcutaneous fat:
alopecia, psoriasis-like rashes, exacerbation of psoriasis, skin rash.
From the side of the musculoskeletal system and connective tissue:
systemic lupus erythematosus, pain in the muscles.
From the urinary system:
Peyronie's disease.
From the reproductive system and the breast:
sexual dysfunction, decreased libido.
Others:
asthenia / fatigue.

Overdose

No cases of overdose of Ganfort were reported; When administered in the form of eye drops, an overdose is unlikely.
Bimatoprost
When unintentionally taking Ganfort inside, the following information can be helpful: there were no symptoms of toxic effects of bimatoprost in doses up to 100 mg / kg / day. during a 2-week oral administration in an experiment in rats and mice.
The dose applied in the study, expressed in mg / m2, exceeds by 70 times the possible dose of bimatoprost in case of accidental ingestion of the contents of the bottle of Ganfort with a child weighing 10 kg.
Timolol
In case of thymolol overdose, the following symptoms can be observed: bradycardia, lowering of arterial pressure, bronchospasm, headache, dizziness, dyspnea, cardiac arrest. Studies have shown that timolol is not completely excreted in hemodialysis. If an overdose occurs, symptomatic therapy is necessary.

Interaction Ganfort with other drugs

Special studies have not been carried out to study the drug interaction of a fixed bimatoprost / timolol combination.
It is possible to potentiate the effects of the combined use of ophthalmic solutions of beta-blockers and the slow calcium channel blockers, guanethidine, beta-blockers, parasympathomimetics, antiarrhythmics (including amiodarone) and cardiac glycosides, which was manifested by a decrease in blood pressure and / or pronounced bradycardia.
Potential systemic effects of beta-blockers have been reported (eg, reduction in heart rate, depression) with simultaneous use of timolol with inhibitors of CYP2D6 (quinidine, fluoxetine, paroxetine).
Periodically reported cases of mydriasis with the simultaneous use of ophthalmic beta-blockers and adrenaline (epinephrine).
Patients using Ganfort with other prostaglandin analogues should be monitored to monitor changes in intraocular pressure.
Very rarely reported cases of calcification of the cornea when combined with phosphate-containing eye drops in some patients with significant damage to the cornea.

special instructions

Just like other ophthalmic drugs, Ganfort can enter the systemic circulation. Due to the presence of timolol, the beta-adrenergic component, various types of adverse reactions (from the cardiovascular and respiratory system), as with systemic beta-blockers, can be observed. Frequency of occurrence of undesirable reactions at local appointment of a preparation is lower, than at system application.
The cardiovascular system
Symptoms of heart failure should be compensated before the use of the drug Ganfort. It is necessary to regularly monitor the condition of patients with severe heart failure, determine the heart rate.
Beta-adrenoblockers can mask symptoms of hypoglycemia, hyperthyrosis and cause a worsening of Prenmetal angina pectoris, severe peripheral and central vascular disorders, and hypotension.
Patients with severe peripheral circulatory disorders (eg severe Raynaud's disease or Raynaud's syndrome) should be cautioned.
Respiratory system
When using timolol, there were reports of side effects on the part of the respiratory organs, including deaths due to bronchospasm in patients with bronchial asthma, and also less often from heart failure.
Other beta-blockers
Timolol may affect intraocular pressure or increase the effect of systemic beta-blockers in patients already receiving a systemic beta-blocker.
Careful observation of such patients is recommended. Also, the use of two local beta-blockers is not recommended.
Anaphylactic reactions
In patients with atonic manifestations in history and severe anaphylactic reactions, various epilephrine (epinephrine) dose allergens, which are commonly used to stop anaphylactic reactions, may not be effective at the foyer of beta-blockers.
Choroidal detachment
There have been reports of cases of choroidal detachment with the use of therapy that reduces the flow of intraocular fluid (eg, timolol, acetazolamide) after filtration surgery.
Surgical anesthesia
Ophthalmic preparations with P-blocking action can suppress systemic effects (3-agonists, for example, adrenaline.
It is necessary to warn the doctor-anesthesiologist about the patient's use of timolol.
Liver
In patients with liver disease of the lung, or initially increased activity of liver enzymes - alapinamiotransferase (AJIT), aspartate aminotransferase (ACT) and / or total bilirubin, bimatoprost had no effect on liver function during a study period of more than 24 months. Data on adverse reactions due to the influence of timolol on liver function are absent.
Body of sight
Before starting treatment, patients should be informed of possible eyelash growth, increased eyelid skin pigmentation and iris pigmentation, since these side effects are established in studies of bimatoprost and Gunfort. Some changes may be permanent, and may be accompanied by the appearance of differences between the eyes, if the drug installations were carried out only in one eye. After the cannabis preparation is canceled, the pigmentation of the iris may remain constant. After 12 months of treatment with Ganfort, the frequency of iris pigmentation was 0.2% in large. And after 12 months of treatment, only bimatoprostom in the form of eye drops 1.5%, further increase in the frequency of this effect was not observed during therapy duration of 3 years.
The increase in pigmentation of the iris is due to the increased production of melanocytes, and not simply by the increase in their number.
The duration of the development of the effect of enhancing the pigmentation of the iris is unknown. The change in the color of the iris seen in the application of bimatoprost may not be expressed in the period from several months to several years. The use of the drug has no effect on nevi or pigment deposition on the iris of the eye. It was reported that the pigmentation of the periorbital region in some patients is reversible.
Perhaps a change in refraction (due to the abolition of therapy with mystical means in individual cases).
Leather
It is possible to grow hair on those areas of the skin, on which the drug was accidentally applied. It is important to apply the drug Ganfort strictly in accordance with the instructions for medical use and to prevent the drug Ganfort from entering the skin.
Auxiliary substances
The benzalkonium chloride supplement, which is part of the Ganfort preparation, can cause irritation of the eye mucosa and a discoloration of soft contact lenses. Contact lenses must be removed prior to the administration of the drug, they can be dressed 15 minutes after the installation.
Benzalkonium chloride can cause acute keratitis and / or toxic corneal ulcer. In this regard, it is necessary to monitor the patient's condition with frequent or prolonged treatment with Ganfort in individuals with dry eye syndrome and with corneal changes.
After opening the vial, it is impossible to exclude the possibility of microbial contamination of its contents, which can lead to inflammatory lesions of the eyes. The shelf life of the drug after the first opening of the bottle is 28 days. After the expiration of the specified time, the vial should be discarded, even if the solution is not completely used.
It is recommended to record on the cardboard pack of the drug the date of opening the vial. Specific guidance As with other ophthalmic medicinal products, Ganfort can enter the systemic bloodstream before being commenced using the Ganfort drug. It is necessary to regularly check the state of insufficiency, determine the frequency of reductions.
When using timolol, there were reports of side effects from the cardiovascular system and respiratory organs, including deaths due to bronchospasm in patients with bronchial asthma, and also less often from heart failure.
Beta-adrenoblockers can mask symptoms of hypoglycemia, hyperthyroidism and cause a worsening of Prinzmetal angina pectoris, severe peripheral and central vascular disorders, and hypotension.
In patients with atopic manifestations in the anamnesis and severe anaphylactic reactions to various allergens, the doses of epinephrine (adrenaline), which are usually used to arrest anaphylactic reactions, against the background of the use of beta-blockers may be ineffective. In patients with hepatic liver disease or initially elevated activity of liver enzymes - alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and / or total bilirubin, bimatoprost had no effect on liver function during the study period of more than 24 months.
Before starting treatment, patients should be informed of possible eyelash growth, increased eyelid skin pigmentation and iris pigmentation, since these side effects are established in studies of bimatoprost and Gunfort®. Some changes may be permanent, and may be accompanied by the appearance of differences between the eyes, if the instillations of the drug were carried out only in one eye. After the cannabis preparation is canceled, the pigmentation of the iris may remain constant. After 12 months of treatment with Ganfort, the frequency of the iris pigmentation was noted in treatment with only bimatoprost in the form of eye drops of 1.5%, a further increase in the frequency of this effect was not observed during therapy lasting 3 years. The increase in pigmentation of the iris is due to the increased production of melanocytes, and not simply by the increase in their number.
The benzalkonium chloride supplement, which is part of the Ganfort preparation, can cause irritation of the eye mucosa and a discoloration of soft contact lenses. Contact lenses must be removed prior to the administration of the drug, they can be dressed 15 minutes after the installation. Benzalkonium chloride can cause acute keratitis and / or toxic corneal ulcer. In this regard, it is necessary to monitor the patient's condition with frequent or prolonged treatment with Ganfort in individuals with dry eye syndrome and with corneal changes.
After opening the vial, it is impossible to exclude the possibility of microbial contamination of its contents, which can lead to inflammatory lesions of the eyes. The shelf life of the drug after the first opening of the bottle is 28 days. After the expiration of the specified time, the vial should be discarded, even if the solution is not completely used.
It is recommended to record on the cardboard pack of the drug the date of opening the vial.
Impact on the ability to manage vehicles and mechanisms
There may be a transient visual impairment after the administration of the drug, so the patient must wait until the vision is fully restored before proceeding to driving the car or controlling the mechanisms.

Form of issue

Eye drops 0.3 mg / ml + 5 mg / ml.
To 3.0 ml of the drug in a dropper bottle of white low-density polyethylene with a capacity of 5 ml with a screw cap made of impact-resistant polystyrene, which is sealed with a polymer film.
For 1 or 3 vials, along with the instructions for use are placed in a cardboard box.

Storage conditions

At a temperature of no higher than 25 ° C.
Keep out of the reach of children
Shelf life - 2 years.
Do not use after the expiration date printed on the package.

Conditions of leave from pharmacies

To buy Ganfort the prescription is not required.