Gunfort eye drops 0.3mg/ml + 5mg/ml 0.4ml vial №30

Mechanism of action

Hanforth is a combination drug, its composition 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 F2a (PGF2a). 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.

Pharmacokinetics

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 vitro studies have shown that bimatoprost penetrates the iris and sclera. When instilled with a 0.03% solution of bimatoprost, 1 drop in both eyes once a day for 2 weeks. C_maxplasma bimatoprost is reached within 10 minutes after administration, and within 1.5 hours its plasma concentration decreases to the lower limit of detection (0.025 ng / ml). Average C_max and the area under the concentration-time curve (AUC_0-24h) bimatopros were close on days 7 and 14, and were 0.08 ng / ml and 0.09 ng × h / ml, respectively, indicating that the equilibrium concentration of bimatoprost is reached during 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, N-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). T_1/2 bimatoprost, determined after intravenous administration, was approximately 45 minutes; and total clearance - 1.5 l / h / kg.

In elderly patients:

When using bimatoprost 2 times a day, the average value of AUC_0-24h in elderly patients, it is 0.0634 ng × h / ml, which significantly exceeds the value of this indicator in healthy young individuals - 0.0218 ng × h / ml.

However, 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 timolol 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. T_1/2 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 of the drug

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.

Dosage and administration

Recommended doses in adults (including elderly patients): 1 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 each instillation.

Side effect

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;

Special senses: 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 soreness, reduced visual acuity, asthenopia, trichiasis; frequency unknown: cystoid macular edema.

Respiratory: infrequently - rhinitis;

On the part of the skin and subcutaneous fat: often - skin pigmentation of the eyelids; infrequently - hirsutism.

Other side effects that were observed when using one of the components of the drug and potentially possible during the period of treatment with the drug Hanforth:

Bimatoprost

Cardiovascular: increase blood pressure.

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

Special senses: allergic conjunctivitis, cataract, darkening of eyelashes, increased iris pigmentation, blepharospasm, eyelid retraction, retinal hemorrhage, uveitis.

Laboratory values: changes in the activity of liver enzymes.

Timolol

Psychological: insomnia, nightmares, decreased libido.

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

Special senses: 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.

Cardiovascular: heart block, cardiac arrest, heart rhythm disturbances, loss of consciousness, bradycardia, heart failure, congestive heart failure; lowering blood pressure, chest pain, cerebrovascular accident, intermittent claudication, Raynaud's syndrome, cold extremities, palpitations.

Respiratory: 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.

Urogenital: Peyronie's disease.

Others: swelling, chest pain, fatigue.

Contraindications

• hypersensitivity to the drug;
• the syndrome of increased reactivity of the respiratory tract, including bronchial asthma in the acute stage and past episodes in history, 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, lactation period.

Carefully: abnormal liver and kidney function (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 Hanforth beta-blocker timolol can mask the 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).

Use during pregnancy and lactation

Contraindicated in pregnancy and lactation.

Application for violations of the liver

With care at dysfunction of a liver.

Application for violations of kidney function

With caution in renal impairment.

Use in children

Contraindicated in children under 18 years.

special instructions

Just like other ophthalmologic drugs, Hanforth can penetrate the systemic circulation.

Symptoms of heart failure should be compensated before the use of the drug Hanforth. Requires regular monitoring of patients with severe heart failure, the determination of heart rate. 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.

Bsta-adrenergic blockers may 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 elevated liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and / or total bilirubin, bimatoprost did not affect liver function during the 4-hour study period of more than 24 months.

Before treatment, patients should be informed about the possible growth of eyelashes, increased eyelid skin pigmentation, and iris pigmentation, since these side effects were established during the study of bimatoprost and Hanforth. Some changes may be permanent, and may be accompanied by the occurrence of differences between the eyes, if the instillation of the drug was performed only in one eye. After withdrawal of the drug Hanforth, pigmentation of the iris may remain constant. After 12 months of treatment with the drug 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 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 Hanforth, 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 Hanforth 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 that the date of opening of the vial be recorded on the carton of the drug.

Impact on the ability to drive vehicles and mechanisms

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.

Overdose

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

Bimatoprost

In case of inadvertent ingestion of drug Hanforth, the following information may be helpful: no toxic effects of bimatoprost were noted in doses up to 100 mg / kg / day.during a 2-week oral administration in an experiment in rats and mice. The dose used in the study, expressed in mg / m, is 70 times higher than the possible dose of bimatoprost when accidentally ingesting the contents of the vial of the drug Ganfort by a child weighing 10 kg.

Timolol

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.

Storage conditions

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

Terms of implementation

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