Pilotimol^® (Drops) Instructions for Use

ATC Code

S01EB51 (Pilocarpine in combination with other drugs)

Active Substances

Pilocarpine (BAN)

Timolol (Rec.INN)

Clinical-Pharmacological Group

Antiglaucoma drug

Pharmacotherapeutic Group

Combined antiglaucoma agent (M-cholinomimetic + beta-adrenergic blocker)

Pharmacological Action

Antiglaucoma drug, contains two active substances.

Pilocarpine is a cholinergic agent that stimulates m-cholinergic receptors. When instilled into the eye, pilocarpine causes miosis and spasm of accommodation, and reduces intraocular pressure. The decrease in intraocular pressure is caused by contraction of the ciliary muscle and the iris muscle, which leads to the widening of the anterior chamber angle and changes the physical structure of the trabecular tissue, thus facilitating the outflow of aqueous humor. The action of pilocarpine lasts from 4 to 14 hours.

Timolol is a beta-blocker that prevents the binding of sympathomimetic neurotransmitters to β₁– and β₂-adrenergic receptors. It reduces intraocular pressure by decreasing the production of aqueous humor. The site of action of timolol is the β₂-adrenergic receptors in the ciliary body. Penetrating into the systemic circulation through absorption via the ocular, nasal, and lacrimal tract mucosa, it can cause systemic effects characteristic of beta-blockers.

The hypotensive effect of timolol begins 20 minutes after instillation, reaches its maximum after 2 hours, and lasts about 24 hours.

When combined in one drug, pilocarpine and Timolol mutually enhance each other’s action (synergism).

Pharmacokinetics

Absorption

Pilocarpine penetrates the cornea well. The C_max of pilocarpine in the aqueous humor is reached after 30 minutes. The C_max of timolol in the aqueous humor is reached after 1-2 hours.

Timolol maleate rapidly penetrates through the cornea into the eye tissues.

Distribution

Pilocarpine binds in many ocular tissues, which prolongs its T_1/2 from the eye. When instilled into the conjunctival sac, pilocarpine does not penetrate into the systemic circulation.

Timolol enters the systemic circulation in small amounts through absorption via the conjunctiva, nasal mucosa, and lacrimal tract.

Metabolism

Pilocarpine is not metabolized in the aqueous humor but is excreted with it.

Timolol is intensively metabolized in the liver.

Excretion

The T_1/2 of pilocarpine from the eye is 1.5-2.5 hours. However, the effect of decreasing intraocular pressure lasts for several hours.

Timolol is excreted in the urine unchanged and as metabolites. The T_1/2 of timolol is 4 hours.

By reducing the formation of intraocular fluid, Timolol reduces the rate of excretion of pilocarpine from the eye.

Pharmacokinetics in special clinical cases

In newborns and young children, the concentration of timolol significantly exceeds its C_max in the plasma of adults.

Indications

• Primary open-angle glaucoma;
• Secondary glaucoma (uveal, aphakic, post-traumatic);
• Angle-closure glaucoma (in combination with miotics);
• Increased intraocular pressure after ophthalmic surgical interventions.

ICD codes

Dosage Regimen

Instill one drop into the affected eye twice daily.

Ensure an interval of approximately 12 hours between administrations.

Do not exceed the recommended dosage.

If using other topical ophthalmic products, administer them at least 5 minutes apart.

To prevent contamination, avoid contact between the dropper tip and the eye, eyelids, or any other surface.

Close the bottle tightly immediately after each use.

Evaluate therapeutic response by measuring intraocular pressure approximately 4 weeks after initiating treatment.

Monitor intraocular pressure at different times of the day to assess the full diurnal curve.

Discontinue all other antiglaucoma medications prior to starting therapy with this drug.

Remove soft contact lenses before instillation and reinsert them no sooner than 15 minutes later due to the presence of benzalkonium chloride.

Adverse Reactions

Local reactions eyelid skin hyperemia, burning and itching in the eyes, eye pain, ciliary muscle spasm, induced myopia, conjunctival hyperemia, lacrimation or decreased tear secretion, photophobia, decreased visual acuity in low light, corneal epithelial edema, transient visual acuity impairment; blepharitis, conjunctivitis. With prolonged use, the development of superficial punctate keratopathy (decreased corneal transparency) and decreased corneal sensitivity is possible, ptosis may occur, rarely – diplopia, reversible lens opacity, dry eye syndrome, increased sweating, asthenia, confusion.

Systemic reactions iris rigidity, iris cyst, retinal detachment, paresthesia, rhinitis, nasal congestion, nosebleed, decreased BP, bradycardia, bradyarrhythmia, AV block, heart failure, cardiac arrest; dizziness, headache, drowsiness, hallucinations, muscle weakness, sexual dysfunction, decreased potency, transient cerebrovascular accident, collapse, depression; dyspnea, bronchospasm, pulmonary insufficiency; nausea, vomiting, diarrhea, allergic reactions (including urticaria).

Contraindications

• Severe corneal dystrophy;
• Iritis;
• Iridocyclitis;
• Bronchial asthma;
• Sinus bradycardia (heart rate <50 beats/min);
• AV block II and III degree;
• Decompensated heart failure;
• Cardiogenic shock;
• Rhinitis;
• COPD;
• Childhood;
• Hypersensitivity to the drug components.

With caution, the drug should be used in retinal detachment, cerebrovascular disorders, diabetes mellitus, thyrotoxicosis, hypoglycemia, oral administration of beta-blockers, as well as before operations under general anesthesia.

Use in Pregnancy and Lactation

During pregnancy, the drug is used if the expected benefit to the mother outweighs the potential risk to the fetus. During the use of the drug, breastfeeding should be discontinued.

Pediatric Use

The drug is contraindicated for use in children.

Special Precautions

Before starting treatment with Pilotimol^®, other antiglaucoma drugs should be discontinued.

Intraocular pressure should be measured at different times of the day.

With long-term administration, the development of resistance to the drug is possible.

Pilotimol^® eye drops contain benzalkonium chloride as a preservative, therefore they are not recommended for use when wearing contact lenses. Before using the drug, contact lenses should be removed and reinserted no earlier than 15 minutes later.

Effect on the ability to drive vehicles and mechanisms

Caution should be exercised when driving a car at night or when working in poor lighting conditions.

Overdose

Symptoms the most common symptoms caused by an overdose of beta-blockers are bradycardia, decreased BP, bronchospasm, and acute heart failure.

Treatment is mainly symptomatic. Atropine can be used as an antidote for pilocarpine. Isoprenaline can be administered intravenously to relieve severe bradycardia or bronchospasm; dobutamine – to treat arterial hypotension.

Drug Interactions

With simultaneous use with calcium channel blockers or cardiac glycosides, impairment of AV conduction, development of acute left ventricular failure or arterial hypotension is possible.

Combined use of Pilotimol^® with drugs that impair catecholamine deposition (reserpine) contributes to the development of arterial hypotension (including orthostatic), bradycardia and dizziness.

Simultaneous use with systemic beta-blockers leads to an enhancement of their pharmacological effect. Pilotimol^® drops should not be used simultaneously with other eye drops containing a beta-blocker.

Storage Conditions

List B. The drug should be stored out of the reach of children, protected from light, at a temperature from 2°C (35.6°F) to 15°C (59°F).

Shelf Life

The shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.