Gunfort eye drops 0.3mg/ml + 5mg/ml 3 ml vial №1

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

Transparent colorless or light yellow solution

combined antiglaucoma remedy (prostaglandin F2-alpha analogue synthetic + beta-blocker)

Pharmacology

Gunfort® is a combination drug, its 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 separately.

Bimatoprost is a synthetic prostamide; its chemical structure is similar to prostaglandin F2α (PGF2α). Bimatoprost does not affect any of the known types of prostaglandin receptors. The hypotensive effect of bimatoprost is due to the increased outflow of intraocular fluid through the trabecula and along the pathway of the eye.

Timolol is a non-selective beta-adrenergic blocker; it does not possess an internal sympathomimetic and membrane stabilizing activity.

Timolol reduces IOP by reducing the formation of intraocular fluid. The exact mechanism of action has not been 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.

Gunfort®

Systemic absorption of the drug is minimal, not different as with combined treatment, and with the instillation of each of the components of the drug separately.

In two studies with a duration of 12 months, no systemic accumulation of any of the active substances was observed.

Bimatoprost

In research in vitro Bimatoprost is shown to penetrate the iris and sclera. With instillation of a 0.03% solution of bimatoprost, 1 drop in both eyes 1 time per day for 2 weeks, the maximum concentration (Cmax) of bimatoprost in the blood plasma is reached within 10 minutes after application, and within 1.5 hours its concentration in plasma blood is reduced to the lower limit of detection (0.025 ng / ml). The mean values ​​of C max and the area under the concentration-time curve (AUC0–24 h) of bimatoprost were close on day 7 and 14 and were 0.08 ng / ml and 0.09 ng / h / ml, respectively, indicating that that the equilibrium concentration of bimatoprost is achieved within the first week of use.

Bimatoprost is moderately distributed in the tissues, and the system volume of distribution when the equilibrium concentration of the drug is reached is 0.67 l / kg. Bimatoprost is predominantly in the blood plasma. The linkage of bimatoprost with plasma proteins is approximately 88%. Bimatoprost undergoes oxidation, K-deethylation and glucuronidation with the formation of various metabolites.

Bimatoprost is excreted primarily by the kidneys. About 67% of the drug, administered intravenously to healthy volunteers, excreted in the urine, and 25% through the gastrointestinal tract (GIT). The half-life (T1 / 2) of bimatoprost, determined after intravenous administration, was approximately 45 minutes; and the total clearance is 1.5 l / h / kg.

In elderly patients:

When using bimatoprost 2 times a day, the average value of AUC0-24 hours in elderly patients is 0.0634 ng / h / ml, which significantly exceeds the value of this indicator in healthy young individuals - 0.0218 ng / h / ml. Nevertheless, this difference has no clinical significance, since the systemic exposure of bimatoprost, when applied locally in elderly patients and healthy young individuals, remains very low. Bimatoprost does not show cumulation in the systemic circulation, the safety profile does not differ in elderly patients and young people.

Timolol

In patients who underwent cataract surgery, after instillation of eye drops in the form of a 0.5% solution, C max of timolol in the intraocular fluid after 1 h was 898 ng / ml. A certain amount of the drug enters the systemic circulation and is metabolized in the liver.T1 / 2 timolol is about 4-6 hours. A part of timolol that has been metabolized in the liver is excreted through the gastrointestinal tract, and the other part and metabolites are excreted by the kidneys. Timolol is slightly bound to plasma proteins.

Indications and usage

Reduction of intraocular pressure (IOP) in patients with open-angle glaucoma and intraocular hypertension with insufficient efficacy of topical application of drugs of the beta-blockers group and prostaglandin analogues.

Contraindications

• Hypersensitivity to the drug components

• Syndrome of increased reactivity of the respiratory tract, including bronchial asthma in the acute stage and past episodes, severe chronic obstructive pulmonary disease (COPD)

• Sinus bradycardia, atrioventricular block II and III degree, clinically severe heart failure, cardiogenic shock

• Age up to 18 years

• Pregnancy, breastfeeding period

Liver and kidney dysfunction (the drug is not well studied in this category of patients). In patients with risk factors for macular edema (for example, with aphakia, pseudophakia, lens rupture). In patients with diabetes mellitus (unstable course) and impaired glucose tolerance, as part of the drug Ganfort® beta-blocker timolol may mask signs of hypoglycemia.

In patients with inflammatory changes in the eyes, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma (there is no data on the study of efficacy and safety).

Dosage 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 drug is missed once, the drug is injected the next day. It is not recommended to exceed the dose - 1 injection 1 time per day. If you use more than 2 drugs, you need to take a 5-minute break between instillations.

Adverse reactions

The frequency of side effects identified during the studies was assessed as follows: very often (> 1/10), often (> 1/100, <1/10); infrequently (> 1/1000, <1/100). The following side effects have been identified in clinical studies of the drug Hanforth®:

From the side of the central nervous system: infrequently - headache.

On the part of the organ of vision: very often - conjunctival hyperemia, eyelash growth; often - superficial keratitis, corneal erosion, burning sensation, itching, burning pain in the eyes, foreign body sensation, dryness of the mucous membrane of the eyes, redness of the eyelids, eye pain, photophobia, discharge from the eyes, blurred vision, eyelid skin itching; infrequently - iridocyclitis, irritation of the mucous membrane of the eyes, conjunctival edema, blepharitis, epiphora, eyelid edema, eyelid tenderness, decreased visual acuity, asthenopia, trichiasis; frequency unknown - Cystoid macular edema.

Part of the respiratory system: infrequently - rhinitis.

From the skin and subcutaneous fat: often - eyelid skin pigmentation; infrequently - hirsutism.

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 Hanforth®:

Infectious and parasitic diseases: infectious disease (catarrhal symptoms and symptoms of lesions of the upper respiratory tract).

From the nervous system: dizziness.

On the part of the organ of vision: allergic conjunctivitis, cataract, darkening of eyelashes, increased iris pigmentation, blepharospasm, eyelid retraction, retinal hemorrhage, uveitis.

Since the cardiovascular system: increase blood pressure.

General violations and changes at the site of administration: asthenia, peripheral edema.

Laboratory values: changes in the activity of liver enzymes.

Mental disorders: insomnia, nightmares, decreased libido.

From the side of the central nervous system: myasthenia gravis, paresthesia, cerebral ischemia.

On the part of the organ of vision: decreased corneal sensitivity, diplopia, ptosis, retinal detachment (after surgical treatment), changes in refraction (due to withdrawal of therapy with miotic agents in some cases), keratitis.

From the organ of hearing and vestibular apparatus: noise in ears.

Since the cardiovascular system: heart block, cardiac arrest, cardiac arrhythmias, loss of consciousness, bradycardia, heart failure, congestive heart failure; lowering blood pressure, chest pain, cerebral circulation, intermittent claudication, Raynaud's syndrome, cold extremities, palpitations.

On the part of the respiratory system: bronchospasm (mainly in individuals with a history of bronchospasm), shortness of breath, cough.

From the gastrointestinal tract: nausea, diarrhea, dyspepsia, dryness of the oral mucosa.

On the part of the skin and subcutaneous fat: alopecia, psoriasis-like rashes, exacerbation of psoriasis.

From the musculoskeletal and connective tissue: systemic lupus erythematosus.

From the urinary system: Peyronie's disease.

Others: swelling, chest pain, fatigue.

No cases of drug overdose were reported to Gunfort®; when administered as an eye drop, overdose is unlikely.

In case of inadvertent ingestion of Ganfort®, the following information may be useful: no symptoms of toxic effects of bimatoprost were noted in doses up to 100 mg / kg / day during 2-week oral administration in an experiment on rats and mice. The dose used in the study, expressed in mg / m2, is 70 times higher than the possible dose of bimatoprost when accidentally ingesting the contents of the vial of Ganfort® as a child with a body weight of 10 kg.

In an overdose of timolol, the following symptoms may be observed: bradycardia, low blood pressure, bronchospasm, headache, dizziness, shortness of breath, cardiac arrest. Studies have shown that timolol is not completely eliminated during hemodialysis. If an overdose occurs, symptomatic therapy is necessary.

Just like other ophthalmologic drugs, Gunforth® can penetrate the systemic circulation. Symptoms of heart failure should be compensated before starting the use of the drug Ganfort®. The regular monitoring of the condition of patients with severe heart failure, the determination of heart rate are necessary. 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 (less often) from heart failure.

Beta-blockers can mask the symptoms of hypoglycemia, hyperthyroidism and cause worsening of Printsmetal's angina, severe peripheral and central vascular disorders, as well as arterial hypotension. In patients with atopic manifestations in history and severe Anaphylactic reactions to various allergens, doses of epinephrine (adrenaline), which are commonly used to relieve anaphylactic reactions, may be ineffective against the use of beta-adrenergic blockers.In patients with pulmonary liver disease or initially increased liver enzyme activity - alanine aminotransferase (ALT), aspartate aminotransferase (AST) and / or total bilirubin bimatoprost did not affect liver function during the study period of more than 24 months.

Before treatment, patients need to be informed about the possible growth of eyelashes, increased eyelid skin pigmentation and pigment of the iris, since these side effects were established during the study of bimatoprost and Hanforth®. 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 discontinuation of Hanforth®, pigmentation of the iris may remain constant. After 12 months of treatment with Hanforth®, the frequency of pigmentation of the iris was observed in 0.2% of patients. And after 12 months of treatment with only bimatoprost in the form of 1.5% eye drops, a further increase in the frequency of this effect was not observed during the course of therapy for 3 years. Increased pigmentation of the iris is due to increased production of melanocytes, and not just an increase in their number. The excipient benzalkonium chloride, which is part of the drug Ganfort®, can cause irritation of the mucous membrane of the eyes and change the color of soft contact lenses. Contact lenses must be removed before the introduction of the drug, you can wear them 15 minutes after instillation. Benzalkoniya 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 patients with dry eye syndrome and with changes in the cornea.

Once the bottle is opened, the possibility of microbial contamination of its contents cannot be ruled out, 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 specified time has elapsed, the bottle should be discarded, even if the solution is not fully used.

It is recommended to write on the carton of the medicinal product the date of opening

vial.

Perhaps a transient visual impairment after drug administration, so the patient must wait until full recovery of vision before proceeding to drive a car or control mechanisms.

Eye drops 0.3 mg / ml + 5 mg / ml. At 3.0 ml of the drug in a dropper bottle made 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. On 1 or 3 bottles droppers together with the application instruction place in a cardboard pack.

At a temperature not higher than 25 ° С. Keep out of the reach of children.

2 years

Do not use beyond the expiration date printed on the package.

On prescription.

- Allergan Pharmaceutical Ireland. Country - Ireland