Monolatan DUO (Drops) Instructions for Use

Marketing Authorization Holder

Laboratoires Théa (France)

Manufactured By

Excelvision (France)

ATC Code

S01ED51 (Timolol in combination with other drugs)

Active Substances

Timolol (Rec.INN registered by WHO)

Latanoprost (Rec.INN registered by WHO)

Dosage Form

Monolatan DUO

Eye drops 0.2 ml: containers 30 pcs.

Dosage Form, Packaging, and Composition

Eye drops in the form of a yellowish opalescent solution.

Excipients: macrogolglycerol hydroxystearate 40 – 50.00 mg, sorbitol – 35.00 mg, macrogol 4000 – 10.00 mg, carbomer – 1.00 mg, disodium edetate – 0.50 mg, sodium hydroxide to pH 6.0, purified water up to 1 ml.

0.2 ml – containers (5) – bags (6) – cardboard packs.

Clinical-Pharmacological Group

Antiglaucoma drug – synthetic prostaglandin F2α analogue + beta-adrenoblocker

Pharmacotherapeutic Group

Antiglaucoma agent – synthetic prostaglandin F_2α analogue

Pharmacological Action

Combined antiglaucoma agent.

Latanoprost is an analogue of prostaglandin F_2α and a selective agonist of FP receptors. It reduces intraocular pressure by increasing the outflow of aqueous humor and has an antiglaucoma effect. The main mechanism of action of latanoprost is associated with an increase in uveoscleral outflow. It does not have a significant effect on the production of aqueous humor and does not affect the blood-ophthalmic barrier.

Timolol is a non-selective β-adrenergic receptor blocker with little intrinsic sympathomimetic and membrane-stabilizing activity. When applied topically, it lowers intraocular pressure by reducing the production of aqueous humor and slightly increasing its outflow.

Pharmacokinetics

Latanoprost

C_max in the aqueous humor (approximately 15-30 ng/ml) is reached 2 hours after instillation into the eye. After application of the eye drops, Latanoprost is distributed primarily in the anterior segment of the eye, the conjunctiva, and the eyelids. Only a small amount of the drug reaches the posterior segment. Latanoprost undergoes hydrolysis in the cornea under the action of esterases to form the biologically active acid.

Metabolism of latanoprost acid in the eye tissues practically does not occur. The main metabolism occurs in the liver. T_1/2 from plasma is 17 min. The main metabolites, 1,2-dinor- and 1,2,3,4-tetranor-metabolites, have no or weak biological activity and are mainly excreted in the urine.

Timolol

When applied topically, timolol rapidly penetrates the cornea. After instillation of the eye drops, C_max of timolol in the aqueous humor of the eye is reached after 1 hour.

T_1/2 from plasma is 6 hours. It enters the systemic circulation in small amounts through absorption by the vessels of the conjunctiva, nasal mucosa, and lacrimal tract. Excretion of timolol metabolites is carried out mainly by the kidneys.

Indications

Open-angle glaucoma; increased intraocular pressure.

ICD codes

Dosage Regimen

Instill one drop into the affected eye(s) once daily.

Administer the dose in the evening for optimal therapeutic effect.

If a dose is missed, apply the next dose at the usual time; do not double the dose.

When using other topical ophthalmic agents, administer them at least 5 minutes apart.

Before instillation, remove contact lenses and reinsert them no sooner than 15 minutes after application.

To prevent contamination, avoid touching the dropper tip to any surface, including the eye.

Discard the container 4 weeks after first opening, even if solution remains.

Use the single-dose container immediately after opening; do not store for later use.

Close the container tightly after each use and store in the original carton to protect from light.

Adverse Reactions

From the organ of vision: visual impairment, blepharitis, cataract, conjunctivitis, allergic lesions of the conjunctiva (including follicles, conjunctival papillary reactions, petechial hemorrhages), corneal lesions (erosions, pigmentation, punctate keratitis), refraction disorders, eye hyperemia, eye irritation, eye pain, increased iris pigmentation, keratitis, photophobia, loss of parts of the visual field.

Infections: sinusitis, upper respiratory tract infections and other infections.

From metabolism and nutrition: diabetes mellitus, hypercholesterolemia.

Mental disorders: depression.

From the nervous system: headache.

From the cardiovascular system: increased blood pressure.

From the skin and subcutaneous tissues: hypertrichosis, rash and skin changes (irritation, chalazion).

From the musculoskeletal system: arthritis.

The following are other adverse events that may be observed during therapy with individual components of this combination (in addition to those listed above).

Latanoprost

From the organ of vision: eye irritation (burning sensation, gritty feeling, itching, tingling and foreign body sensation); transient punctate epithelial erosions, eyelid edema, corneal edema and erosions; eyelash and vellus hair lengthening, thickening, increased number and increased pigmentation; iritis/uveitis; macular edema, including cystoid; change in the direction of eyelash growth, sometimes causing eye irritation; blurred vision.

From the skin and subcutaneous tissues: skin rash, darkening of the skin of the eyelids and local skin reactions on the eyelids.

From the nervous system: dizziness.

From the respiratory system: bronchospasm (including acute attacks or exacerbation of the disease in patients with a history of bronchial asthma), dyspnea.

From the musculoskeletal system muscle/joint pain.

General and local reactions nonspecific chest pain.

Timolol (in the form of eye drops)

From the immune system systemic allergic reactions, including anaphylaxis, angioedema, urticaria, localized and generalized rash.

From metabolism and nutrition anorexia, masking of hypoglycemia symptoms in diabetic patients.

Mental disorders behavioral and mental disorders, including confusion, hallucinations, anxiety, disorientation, nervousness, memory loss, decreased libido, insomnia and nightmares.

From the nervous system cerebral ischemia, acute cerebrovascular accidents, dizziness, exacerbation of myasthenia gravis symptoms, paresthesia, drowsiness, fainting.

From the organ of vision cystoid macular edema, decreased corneal sensitivity; choroidal detachment after filtration surgery; ptosis, visual disturbances, including refraction changes and diplopia.

From the ear and vestibular system tinnitus.

From the cardiovascular system arrhythmia, bradycardia, cardiac arrest, heart failure, intracardiac conduction block, palpitations, progression of angina pectoris, intermittent claudication, cold hands and feet, decreased blood pressure, Raynaud’s syndrome.

From the respiratory system bronchospasm (mainly in patients with previous bronchospastic diseases), cough, dyspnea, nasal congestion, pulmonary edema and respiratory failure.

From the digestive system diarrhea, dry mouth, dyspepsia, nausea, retroperitoneal fibrosis.

From the skin and subcutaneous tissues alopecia, pseudopemphigoid, psoriasis-like rash or exacerbation of psoriasis.

From the musculoskeletal system systemic lupus erythematosus.

From the reproductive system and mammary glands impotence, Peyronie’s disease.

General and local asthenia/fatigue, chest pain, edema.

Contraindications

Bronchial asthma or a history of bronchial asthma; COPD; sinus bradycardia; second- or third-degree AV block; decompensated chronic heart failure of class II-III; cardiogenic shock; age under 18 years; lactation (breastfeeding).

With caution

Inflammatory, neovascular, closed-angle or congenital glaucoma, open-angle glaucoma combined with pseudophakia, pigmentary glaucoma, aphakia, pseudophakia with rupture of the posterior lens capsule, presence of risk factors for macular edema (cases of macular edema, including cystoid, have been described during treatment with latanoprost).

Use in Pregnancy and Lactation

Adequate and strictly controlled clinical studies on the safety of the drug during pregnancy and lactation (breastfeeding) have not been conducted. Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus or child.

Contraindicated for use during breastfeeding.

Pediatric Use

Contraindicated for use under 18 years of age.

Special Precautions

During use, a gradual change in eye color may occur due to an increase in the amount of brown pigment in the iris; periodic observation by the attending physician is recommended.

Effect on ability to drive vehicles and operate machinery

Instillation of eye drops may cause a transient feeling of “a veil before the eyes” for a few minutes, which must be taken into account when driving a car and working with moving machinery. Until this effect disappears, patients should not drive a car or use complex machinery.

Drug Interactions

With simultaneous use with slow calcium channel blockers, drugs that reduce catecholamine activity, beta-blockers, antiarrhythmic drugs (including amiodarone and quinidine), cardiac glycosides, cholinomimetics, opioid analgesics and MAO inhibitors, an increase in the hypotensive effect and/or the development of severe bradycardia is possible.

When timolol was used simultaneously with epinephrine, mydriasis sometimes developed.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.