Fotil® [Pilocarpine, Timolol]

Pharmacological properties

Fotil and fotil forte are a combination of pilocarpine and timolol - drugs that reduce intraocular pressure.

The chemical name of pilocarpine is: 3 - ethyl-4 - [(1-methylimidazol-5-yl) methyl] tetrahydrofuran-2-one. Used in the form of hydrochloride. The chemical name of timolol maleate is: (S) -1- [1,1-dimethiethyl) amino] -3 [[4- (4-morpholinyl) -1,2,5-thiadiazol-3-yl] -oxy] -2- propanol. (Z) -butenedioate (1: 1) salt. The structure of the compound has an asymmetric carbon atom, and the levorotatory isomer of the compound is included in the composition of the Fotil eye drops.

Pilocarpine is a parasympathomimetic, a stimulator of M-cholinergic receptors. When instilled into the eyes, it reduces intraocular pressure, causes miosis and accommodation spasm. Reducing intraocular pressure is achieved by reducing the ciliary and circular muscles of the iris, which is accompanied by an increase in the anterior chamber angle and changes the organization of the trabecular tissue, thereby facilitating the outflow of aqueous humor. When instilling a solution of pilocarpine in the eye, the drug penetrates well into the cornea. Its maximum concentration in aqueous humor is reached after 30 minutes. It spreads in the tissues of the eye, the half-life of them is 1.5–2.5 hours. Accommodation spasm and constriction of the pupil are observed 10 minutes after instillation and persist for 1–2 hours. A decrease in intraocular pressure persists for several hours. Pilocarpine is not metabolized in aqueous humor, but is eliminated with its outflow. The simultaneous use of timolol, which reduces the production of aqueous humor, reduces the rate of elimination of pilocarpine. Resorbed pilocarpine in the blood and liver tissue is hydrolyzed to inactive metabolites. The elimination half-life from blood plasma is 30 minutes.

Timolol is a β-adrenergic receptor blocker that effectively inhibits the interaction of sympathomimetic neurotransmitters with β₁- and β₂-adrenoreceptors. Reduces intraocular pressure by reducing the production of aqueous humor. Affects β₂-adrenoreceptors of the ciliary body.

It does not have an ICA, a local anesthetic (membrane-stabilizing) effect, and does not affect blood circulation in the retina. When instilling eyes, a certain amount of timolol is absorbed and enters the systemic circulation, through the nasolacrimal canal enters the digestive tract, which can lead to the development of undesirable systemic effects, primarily from the cardiovascular and respiratory systems.

When administered orally, timolol is well absorbed; undergoes active presystemic metabolism. It is secreted mainly by the kidneys in the form of inactive metabolites; the elimination half-life is about 4 hours. It penetrates well through the cornea. A decrease in intraocular pressure with topical administration of the drug usually develops after 2 hours. The maximum effect is observed after 3-4 hours, the duration of action is 10-20 hours.

With the combination of pilocarpine and timolol in one drug, an additive effect is observed with respect to reducing intraocular pressure, since the mechanisms of action of timolol and pilocarpine are different. When applied topically, Fotil reduces both increased and normal intraocular pressure. After instillation of Fotil, intraocular pressure usually begins to decrease after 30 minutes. The maximum effect is noted after 2 hours, and a significant decrease in intraocular pressure with a single injection can persist for 20 hours.

Indications

Open-angle and angle-angle glaucoma, glaucoma associated with aphakia; recent secondary glaucoma; as an additional tool in the treatment of glaucoma with other drugs; with an increase in intraocular pressure, including in the postoperative period.

Application

Usually, 1 drop of fotil is prescribed in the affected eye (s) 2-3 times a day.Fotil Forte is prescribed 1 drop 2 times a day. since some patients need several weeks to stabilize the decrease in intraocular pressure caused by the drug, the effectiveness of the fotil should be evaluated approximately 4 weeks after the start of treatment. if intraocular pressure is maintained at a satisfactory level, then the dose of the drug can be reduced to 1 drop 1 time per day in the affected eye.

Increasing the dose of Fotil Forte (more than 1 drop 2 times a day) does not lead to a further decrease in intraocular pressure. If intraocular pressure is still high at this dose, dipipephrine therapy and / or systemic use of carbonic anhydrase inhibitors (e.g., acetazolamide) should be prescribed simultaneously.

Contraindications

Cholinergic drugs (pilocarpine) are contraindicated in acute iritis, as well as with damage to the cornea. β-adrenergic receptor blockers (timolol) are contraindicated for patients with BA or if they have a history of it, as well as for hobl, sinus bradycardia, degree II – III av blockade, severe heart failure, cardiogenic shock, and hypersensitivity to any of the components of the drug.

Side effects

When applying eye drops containing pilocarpine, the following local adverse reactions are possible: rapidly passing burning and acute pain, ciliary muscle spasm, hyperemia of the conjunctival vessels, headache in the temporal and infraorbital regions, induced myopia. such reactions are observed, as a rule, in young people who have recently begun treatment with pilocarpine. decreased visual acuity in poor lighting conditions is caused by myosis. with the use of myotic agents, rare cases of retinal detachment, iris rigidity, and the formation of iris cysts have been noted. with prolonged use of pilocarpine, cases of reversible opacification of the lens were observed. with local use of β-adrenoreceptor blockers, the following local adverse reactions were observed: corneal anesthesia, point keratitis, dry eye syndrome, allergic blepharoconjunctivitis. with prolonged use of the drug in patients with glaucoma, resistance to pilocarpine and timolol may develop.

Of the systemic reactions, nausea, diarrhea, increased sweating, salivation, decreased blood pressure, asthma attacks, congestive heart failure, arrhythmia, hypotension, hallucinations, confusion, headache, asthenia, hyperemia of the nasal mucosa, rarely depression, paresthesia, and pain are possible. in the extremities, increased fatigue, anxiety, anorexia, retroperitoneal fibrosis, impotence, pain in the abdomen, purple.

special instructions

Safety and efficacy of the drug in children have not been established.

Prescribing Fotil during pregnancy is allowed only if the expected benefit to the expectant mother outweighs the potential risk to the fetus. In view of the possible serious effects of timolol on the baby, the question of whether to continue or stop breastfeeding should be considered taking into account the need for this drug to treat the mother.

Myosis usually causes difficulty in adapting to the dark. Patients taking Photil should be careful when driving vehicles at night. With oral administration of β-adrenergic receptor blockers at the same time as Photil, an additive effect may be observed with respect to the effect on intraocular pressure or the systemic effect of β-adrenergic receptor blockers. Also, Photil should not be prescribed simultaneously with other β-adrenergic receptor blockers used in ophthalmic practice.

Fotil and Fotil Forte should be used with caution in patients with impaired cerebral circulation.In the event of symptoms of cerebrovascular accident, consideration should be given to the appointment of another type of therapy. There are separate reports that blockade of β-adrenergic receptors can lead to muscle weakness due to certain myasthenic symptoms (eg, diplopia, ptosis, general weakness). With prolonged (for several years) use of Fotil and Fotil Forte, as well as when using other anti-glaucoma drugs, tolerance to them can develop.

The drug is able to exert a systemic effect after resorption up to bronchospasm in patients with AD and heart failure. The use of Fotil should be discontinued when the first symptoms of heart failure appear. Patients with COPD Photil should not be prescribed. However, if necessary, the drug should be used with extreme caution.

Preparations Fotil and Fotil Forte should also be used with caution when conducting selective surgical interventions using anesthetics. The gradual cessation of β-adrenoreceptor blockers prior to surgery is recommended; this reduces the risk of developing arterial hypotension and asystole during anesthesia.

Before using the drug, contact lenses should be removed; they can be installed again no earlier than 15 minutes after instillation of the drug.

Interactions

Caution should be exercised with the simultaneous use of fotil and calcium ion antagonists, both when taken orally and when given intravenously due to possible violations of av-conduction, left ventricular failure, arterial hypotension. patients with cardiac abnormalities should not be prescribed these drugs at the same time.

Overdose

In case of an overdose of parasympathomimetic agents and systemic β-adrenoreceptor blockers, bradycardia, arterial hypotension, bronchospasm, and acute heart failure may occur.

The treatment is symptomatic. Atropine is used as the antidote for pilocarpine. With severe bradycardia or bronchospasm, isoprenaline is administered iv, with severe hypotension - dobutamine, oxygen therapy is prescribed.

Storage conditions

In the dark place at a temperature of 2-8 ° C; an open bottle can be stored at room temperature, the drug should be used within 1 month.