Monoprost®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MONOPROST® (MONOPROST®)

Composition:

Active substance: latanoprost;

1 ml of ophthalmic solution contains 50 mcg of latanoprost;

1 drop contains approximately 1.5 mcg of latanoprost;

Excipients: polyoxyl 35 castor oil, hydrogenated; sorbitol (E 420), carbomer, macrogol 4000, disodium edetate, sodium hydroxide, water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: opalescent solution, practically free from particles. The solution is slightly yellow, pH 6.5–7.5, osmolality 250–310 mOsmol/kg.

Pharmacotherapeutic group. Ophthalmological agents. Anti-glaucoma agents and miotics. Analogues of prostaglandins. ATC code S01E E01.

Pharmacological properties.

Pharmacodynamics.

The active substance latanoprost, a prostaglandin F2α analog, is a selective agonist of the prostaglandin FP receptor, which reduces intraocular pressure by increasing the outflow of aqueous humor. Reduction of intraocular pressure in humans begins approximately 3–4 hours after administration of the drug, with maximum effect reached within 8–12 hours. The hypotensive effect lasts for at least 24 hours.

The drug is effective as monotherapy. In addition, latanoprost is effective in combination with beta-adrenergic blockers (timolol). The effect of latanoprost is additive when used in combination with adrenergic agonists (dipivalyl epinephrine), oral carbonic anhydrase inhibitors (acetazolamide), and at least partially additive when used with cholinergic agonists (pilocarpine).

Latanoprost does not significantly affect the production of intraocular fluid. No effect of latanoprost on the blood-ocular barrier has been demonstrated.

Latanoprost did not cause leakage of fluorescein in the posterior segment of the human eye in pseudophakia.

It has been established that latanoprost, at therapeutic doses, exerts no pharmacological effect on the cardiovascular and respiratory systems.

Pharmacokinetics.

Latanoprost is a prodrug. Its isopropyl ester, which is inactive per se, is absorbed through the cornea after ocular instillation and hydrolyzed by corneal esterases to the biologically active acid.

Maximum concentration in the aqueous humor is achieved approximately 2 hours after topical administration. Latanoprost is distributed mainly in the anterior segment, conjunctiva, and eyelids. Only a negligible amount of the drug reaches the posterior segment.

The drug is not significantly metabolized in the eye. The main metabolism of latanoprost occurs in the liver. The plasma half-life is 17 minutes.

Clinical characteristics.

Indications.

For lowering elevated intraocular pressure in adult patients, including elderly patients with open-angle glaucoma and elevated intraocular pressure.

Contraindications.

Known hypersensitivity to any component of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

There are insufficient data on the interaction of latanoprost with other medicinal products.

Paradoxical increase in intraocular pressure has been reported after concomitant topical ocular administration of two prostaglandin analogues. Therefore, concomitant use of two or more prostaglandins, prostaglandin analogues, or their derivatives is not recommended.

Drug interaction studies have been conducted only in adult patients.

Special precautions for use.

Latanoprost may cause a gradual change in eye colour due to increased brown pigmentation in the iris. Patients should be informed about the possibility of a permanent change in eye colour prior to initiating treatment. Treatment of only one eye may lead to permanent heterochromia.

Colour changes in the eye are observed predominantly in patients with mixed iris colouring, such as blue-brown, gray-brown, yellow-brown or green-brown. Colour changes usually occurred within the first 8 months of treatment, rarely during the second or third year, and were not observed after the fourth year of treatment. The progression of iris pigmentation decreases over time and stabilizes after 5 years. The effect of increased pigmentation after 5 years of treatment with the drug has not been evaluated. In a 5-year safety study of latanoprost, increased iris pigmentation was reported in 33% of patients (see section "Adverse reactions"). Changes in iris colour are mostly mild and often clinically insignificant. The incidence of cases in patients with mixed iris colour ranged from 7 to 85%, with the highest frequency observed in patients with yellow-brown iris colour. Eye colour changes were not observed in patients with uniformly blue iris colour and were rare in patients with uniformly gray, green or brown iris colour.

The change in colour occurs due to increased melanin content in the iris stromal melanocytes, not due to an increase in the number of melanocytes. Typically, brown pigmentation starts around the pupil and spreads concentrically toward the periphery of the affected eye, although the entire iris or parts of it may become more brownish. After discontinuation of treatment, further progression of brown iris pigmentation has not been observed. There are no data indicating that this phenomenon is associated with any symptoms or pathological changes.

No changes in iris nevi or freckles have been noted under the influence of therapy. There was no observed accumulation of pigment in the trabecular meshwork or any other part of the anterior chamber of the eye. Increased iris pigmentation does not lead to clinical complications, and the drug may be continued even if iris pigmentation has changed. However, patients should undergo regular ophthalmic examinations, and treatment should be discontinued if the clinical situation requires it.

Experience with the use of latanoprost is limited in chronic angle-closure glaucoma, open-angle glaucoma in pseudophakic patients, and pigmentary glaucoma. Currently, there are no data on the use of latanoprost in inflammatory or neovascular glaucoma or in inflammatory eye diseases. MONOPROST**®** has no or negligible effect on the pupil, but data on its use during acute attacks of angle-closure glaucoma are lacking. Therefore, the drug should be used with caution in such conditions.

Data on the use of the drug during the perioperative period in cataract surgery are limited. The drug should be used with caution in such patients.

The drug should be used with caution in patients with a history of herpetic keratitis. In cases of active keratitis caused by herpes simplex virus, and in patients with a history of recurrent herpetic keratitis, especially associated with prostaglandin analogues, the use of the drug should be avoided.

Cases of macular edema have been reported (see section "Adverse reactions**"**) primarily in aphakic patients, pseudophakic patients with rupture of the posterior lens capsule or anterior chamber lens implantation, and patients with known risk factors for cystoid macular edema (such as diabetic retinopathy and retinal vein occlusion).

Therefore, the drug should be used with caution in the above-mentioned patients.

The drug may be used with caution in patients with known risk factors for development of iritis/uveitis.

Experience with the use of the drug in patients with bronchial asthma is limited, although there have been reports of some cases of asthma exacerbation and/or dyspnea. The drug should be prescribed with caution to patients with bronchial asthma; see also section "Adverse reactions".

Changes in skin colour in the periorbital area have been observed, with most cases reported in Japanese patients. Current data suggest that skin pigmentation changes in the periorbital area are not permanent and in some cases resolve during continued treatment with the drug.

Latanoprost may gradually change the eyelashes and vellus hair around the treated eye and adjacent areas; these changes include increased length, thickness, pigmentation, and number of eyelashes or vellus hairs, as well as misdirected eyelash growth. Changes in eyelashes are reversible and resolve after discontinuation of the drug.

MONOPROST**®** contains macrogolglycerol hydroxystearate (polyoxylated hydrogenated castor oil) and may cause skin allergic reactions; see section "Adverse reactions". Currently, there are insufficient data on the safety of this excipient for long-term use.

Use during pregnancy or breastfeeding.

Fertility.

Animal studies revealed no effect of latanoprost on reproductive function in either sex.

Pregnancy.

The safety of this medicinal product for use in pregnant women has not been established. Its pharmacological action poses a potential risk to pregnancy, the fetus, or the newborn. Therefore, the drug should not be used during pregnancy.

Breastfeeding.

Latanoprost and its metabolites may pass into breast milk; therefore, women who are breastfeeding should discontinue treatment with the drug or discontinue breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

MONOPROST**®** has a negligible effect on the ability to drive or operate machinery. As with other ophthalmic preparations, instillation of eye drops may cause temporary blurred vision.

Until this effect subsides, patients should not drive or operate machinery until visual acuity is restored.

Method of Administration and Dosage

Recommended dose for adults, including elderly patients: 1 drop in the affected eye once daily. The optimal effect is achieved when the medication is administered in the evening.

MONOPROST® should not be used more frequently than once daily, as increased frequency of administration has been shown to reduce the effectiveness of intraocular pressure reduction.

If a dose is missed, continue treatment by administering the next dose at the usual time.

As with any ophthalmic drops, to minimize potential systemic absorption, it is recommended to press on the lacrimal sac at the medial canthus of the eye for 1 minute immediately after instillation of each drop.

Before instilling ophthalmic drops, contact lenses should be removed. They may be reinserted 15 minutes after instillation.

When using multiple ophthalmic topical agents, the medications should be administered at least 5 minutes apart.

Instructions for use:

1. Wash your hands and stand or sit comfortably.
2. Gently pull down the lower eyelid of the affected eye with your finger.
3. Bring the tip of the open single-dose container as close as possible to the eye, without touching the eye surface.
4. Gently squeeze the container so that one drop falls into the eye, then release the lower eyelid.

1. Close the eye and press with a finger on the inner corner of the treated eye for 1 minute.

1. Repeat all the above steps for the second eye, if prescribed by the doctor.
2. The single-dose container with any remaining contents should be discarded immediately after use. Do not store for future use.

Children. Not to be used in children (under 18 years of age).

Overdose.

Apart from eye irritation and conjunctival hyperemia, no other ocular adverse effects have been reported in cases of overdose.

The following information may be useful in case of accidental ingestion. One vial contains 10 mcg of latanoprost. More than 90% of latanoprost is metabolized during first-pass liver metabolism. Intravenous infusion of latanoprost at a dose of 3 mcg/kg in healthy volunteers did not cause any symptoms; however, doses of 5.5–10 mcg/kg caused nausea, abdominal pain, dizziness, increased fatigue, flushing, and sweating.

No bronchospasm was observed in patients with mild to moderate bronchial asthma when latanoprost doses 7 times higher than the clinical dose were administered topically to the eyes.

In case of overdose, symptomatic treatment should be administered.

Adverse Reactions

Most adverse reactions are related to the eye. Increased pigmentation of the iris has been reported during treatment with latanoprost. Other adverse reactions are generally transient and occur only at the time of instillation.

Infections and parasitic diseases: Herpetic keratitis*§.

Nervous system disorders: Headache*, dizziness*.

Eye disorders: Increased pigmentation of the iris; mild to moderate conjunctival hyperemia; ocular irritation (burning sensation with feeling of "sand in the eye", itching, stinging or foreign body sensation in the eye); changes in eyelashes and vellus hair (increased length, thickness, pigmentation, and number); punctate keratitis, mostly asymptomatic; blepharitis; eye pain; photophobia; eyelid edema; dry eye; keratitis*; blurred vision; conjunctivitis*; iritis*; uveitis*; macular edema, including cystoid macular edema*; corneal edema*; corneal erosions; periorbital edema; trichiasis* (misdirected eyelash growth, sometimes causing ocular irritation); distichiasis (presence of an extra row of eyelashes near the meibomian gland orifices); local skin reaction on the eyelids; periorbital changes and eyelid changes leading to deepening of the eyelid fold; iris cyst*§; darkening of the palpebral skin of the eyelids; ocular mucous membrane pseudopemphigoid*§.

Cardiac disorders: Angina pectoris*, unstable angina, palpitations*.

Respiratory, thoracic and mediastinal disorders: Dyspnea*, exacerbation of bronchial asthma, shortness of breath*.

Gastrointestinal disorders: Nausea*, vomiting*.

Skin and subcutaneous tissue disorders: Skin rash, pruritus.

Musculoskeletal and connective tissue disorders: Myalgia*, arthralgia*.

General disorders and administration site conditions: Chest pain*.

Note

* Adverse reaction to the medicinal product identified in the post-marketing period.

§ Frequency of the adverse reaction to the medicinal product was assessed according to the "Rule of Three".

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions.

Please send information to: [email protected] or by phone: (044) 467-57-70 (24/7), 585-04-60.

Shelf life. 2 years when stored in the outer packaging.

After first opening of the sachet, use the single-dose containers within 10 days.

After first opening of the single-dose container, its contents should be used immediately and the single-dose container should be discarded.

Storage conditions. Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 0.2 mL in a single-dose container; 5 single-dose containers connected together in a strip (strip), packed in a sachet; 6 sachets (No. 30) in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

EXCELVISION/EXCELVISION.

Manufacturer's address and place of business.

Zone Industrielle de la Lombardiere, 27 rue de la Lombardiere, ANNONAY, 07100, France

Marketing Authorization Holder.

LABORATOIRES THEA/LABORATOIRES THEA.

Address of the Marketing Authorization Holder and/or its representative.

12 rue Louis Bleriot, 63100 CLERMONT-FERRAND CEDEX 2, France