Monosopt

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MONOSOPT (MONOSOPT)

Composition:

Active substance: dorzolamide;

1 ml of solution contains dorzolamide hydrochloride equivalent to dorzolamide 20 mg;

Excipients: benzalkonium chloride solution, mannitol, sodium citrate, hydroxyethylcellulose, sodium hydroxide (for pH adjustment), water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear, colorless to almost colorless, slightly viscous solution.

Pharmacotherapeutic group. Anti-glaucoma preparations and miotics. Carbonic anhydrase inhibitors. Dorzolamide. ATC code S01E C03.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Carbonic anhydrase is an enzyme present in many tissues of the body, including ocular tissues. In the human body, carbonic anhydrase exists in the form of several isoenzymes, the most active of which is carbonic anhydrase-II (CA-II), primarily found in erythrocytes and other tissues. Inhibition of carbonic anhydrase in the ciliary body of the eye reduces the secretion of aqueous humor. This results in a reduction of intraocular pressure (IOP).

Monosopt contains dorzolamide hydrochloride, a potent inhibitor of carbonic anhydrase-II. After topical administration, it reduces IOP, whether associated or not associated with glaucoma. Elevated IOP is a major risk factor for optic nerve damage or visual field loss. Monosopt does not cause miosis and reduces IOP without such adverse effects as night blindness or accommodation spasm. The effect of the drug on pulse rate and blood pressure is minimal or absent.

Beta-adrenergic blockers for topical use also reduce IOP but have a different mechanism of action. Therefore, the combined use of beta-blockers with dorzolamide provides an additive reduction in IOP. These data are consistent with reports on the additive effect of combining beta-blockers with oral carbonic anhydrase inhibitors.

Pharmacokinetics

Unlike oral carbonic anhydrase inhibitors, dorzolamide hydrochloride, when applied topically, acts directly in the eye at significantly lower doses, thus producing less pronounced systemic effects. In clinical studies, this resulted in reduced IOP without the acid-base or electrolyte imbalances commonly associated with oral carbonic anhydrase inhibitors.

After topical application, dorzolamide reaches the systemic circulation. To assess the level of systemic carbonic anhydrase inhibition following topical administration, concentrations of the active substance and its metabolites in plasma and erythrocytes, as well as the degree of inhibition of carbonic anhydrase activity in erythrocytes, were measured. With prolonged use, dorzolamide accumulates in erythrocytes due to selective binding to CA-II, while very low concentrations of free active substance are maintained in plasma. One N-desethylated metabolite is formed from the parent compound, which inhibits CA-II to a lesser extent than the original compound but also inhibits the less active isoenzyme CA-I. The metabolite also accumulates in erythrocytes, where it binds predominantly to CA-I. Dorzolamide is moderately bound to plasma proteins (approximately 33%) and is excreted in urine (mainly unchanged), as is its metabolite. After discontinuation of treatment, nonlinear elimination of dorzolamide from erythrocytes occurs, initially resulting in a rapid decline in active substance concentration, followed by a slower elimination phase with a half-life of approximately 4 months.

Following oral administration to model maximum systemic exposure to dorzolamide after prolonged topical ophthalmic use, steady-state conditions were achieved within 13 weeks. At steady state, neither free active substance nor metabolite was practically detectable in plasma; carbonic anhydrase inhibition in erythrocytes was less than that considered necessary for pharmacological effects on renal or respiratory function. Similar pharmacokinetic results were observed after prolonged topical use of dorzolamide. However, in some elderly patients with renal impairment (creatinine clearance of 30–60 mL/min), metabolite concentrations in erythrocytes were higher, although this was not accompanied by significant differences in carbonic anhydrase inhibition; clinically significant systemic adverse reactions directly related to these findings were not observed.

Clinical Characteristics.

Indications.

Treatment of elevated intraocular pressure in patients with:

• ocular hypertension;
• open-angle glaucoma;
• pseudoexfoliative glaucoma;
• as adjunctive therapy to beta-blockers or as monotherapy when treatment with beta-blockers has been unsuccessful or beta-blockers are contraindicated.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Severe renal impairment (CrCl < 30 mL/min).

Hyperchloremic acidosis.

Interaction with other medicinal products and other forms of interaction.

Specific studies on the interaction of dorzolamide with other medicinal products have not been conducted.

In clinical studies, concomitant use of dorzolamide with timolol ophthalmic solution; betaxolol ophthalmic solution; systemically administered medicinal products, including ACE inhibitors, calcium channel blockers, diuretics, NSAIDs (e.g., acetylsalicylic acid), and hormones (estrogen, insulin, thyroxine) did not show any signs of adverse reactions due to interaction.

During glaucoma treatment, the interaction between concomitant use of dorzolamide and miotics or adrenergic agonists has not been fully investigated.

Special precautions for use

There are no data on the use of dorzolamide in patients with hepatic impairment; therefore, the drug should be used with caution in such patients.

The management of patients with acute angle-closure glaucoma requires additional therapy beyond lowering intraocular pressure. The use of dorzolamide in patients with acute angle-closure glaucoma has not been studied.

Dorzolamide contains a sulfonamide group, similar to sulfonamides, and even with topical administration is systemically absorbed. Therefore, when dorzolamide is administered topically, adverse reactions typical of systemic sulfonamide use may occur, including severe reactions such as Stevens–Johnson syndrome and toxic epidermal necrolysis. If early signs of severe reactions or hypersensitivity appear, the drug should be discontinued immediately.

The use of oral carbonic anhydrase inhibitors has been associated with the development of urolithiasis due to disturbances in acid-base balance, particularly in patients with a history of nephrolithiasis. Although acid-base disturbances have not been observed with dorzolamide, rare cases of urolithiasis have been reported. Since dorzolamide, as a topically applied carbonic anhydrase inhibitor, is systemically absorbed, patients with a history of nephrolithiasis who are treated with dorzolamide may have an increased risk of developing urolithiasis.

If allergic reactions (e.g., conjunctivitis or eyelid reactions) occur, discontinuation of the drug should be considered.

Concomitant use with dorzolamide may potentiate the systemic effects of oral carbonic anhydrase inhibitors. Therefore, concomitant use of oral carbonic anhydrase inhibitors and dorzolamide is not recommended.

Corneal edema and irreversible corneal decompensation have been reported in patients with pre-existing chronic corneal abnormalities and/or a history of intraocular surgery during treatment with dorzolamide. Dorzolamide for topical use should be administered with caution in such patients.

After filtration surgery using aqueous suppressants, choroidal detachment with ocular hypotony has been reported.

The drug Monosopt contains benzalkonium chloride, which may cause eye irritation, symptoms of dry eye, and may affect the tear film and corneal surface. Use with caution in patients with dry eye syndrome and those at risk of developing asymmetric aberrations.

Contact lenses should be removed before instilling the medication and not reinserted until at least 15 minutes after administration. Benzalkonium chloride may discolor soft contact lenses; therefore, contact with lenses should be avoided.

Use during pregnancy or breastfeeding

Dorzolamide should not be used during pregnancy, as adequate clinical data on its use in pregnant women are lacking. In rabbits, dorzolamide showed teratogenic effects at doses that were toxic to the mother.

It is unknown whether dorzolamide is excreted in human breast milk; therefore, the drug should not be used during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Specific studies on the effect of dorzolamide on reaction speed have not been conducted.

No negative effect of Monosopt eye drops on the ability to drive or operate machinery is expected.

Dosage and Administration

If Monopt is used as monotherapy, instill 1 drop into the affected eye(s) 3 times daily.

In adjunctive therapy with beta-adrenergic blocking ophthalmic solutions, instill 1 drop of Monopt into the conjunctival sac of the affected eye(s) 2 times daily.

When replacing another topical anti-glaucoma medication with dorzolamide, discontinue therapy with the previous agent and begin treatment with Monopt the following day.

During administration of the medication, avoid contact between the dropper tip and the surface of the eye or surrounding skin, as ophthalmic solutions may become contaminated with microorganisms, which may cause ocular infection. Use of contaminated solution may lead to severe ocular injury with possible vision loss.

Application of nasolacrimal occlusion or closing the eyelids for 2 minutes reduces systemic absorption, thereby decreasing systemic adverse effects and increasing local activity.

• Wash hands before instillation.
• Take the dropper bottle and unscrew the protective cap.
• After removing the cap, if the protective ring around the dropper rotates freely, remove it before instillation.
• Hold the bottle pointing downward between the index and middle fingers.
• Tilt the head backward. Pull the lower eyelid gently with a clean finger until a "pocket" forms between the eyelid and the eye. The drop should be instilled into this pocket (Fig. 1).
• Bring the tip of the bottle close to the eye. For convenience, this can be done in front of a mirror.
• Do not touch the dropper tip to the eye, eyelid, surrounding areas, or any other surfaces, to avoid contaminating the remaining solution in the bottle.
• Gently press the base of the bottle to release one drop at a time (Fig. 2).
• After instilling Monopt drops, press with a finger at the inner corner of the eye near the nose for 2–3 minutes (Fig. 3). This helps prevent the medication from draining into the nose and systemic circulation, especially important in newborns and young children.
• If instilling drops into both eyes, wash hands before instilling into the second eye to prevent spreading infection from one eye to the other.
• Immediately after use, tightly replace the cap on the bottle.

If a drop misses the eye, repeat the instillation.

Do not use the medication in any way other than as directed by the physician.

If more than one ophthalmic medication is required, the interval between instillations should be at least 5 minutes. Ophthalmic ointments should be administered last.

Pediatric Use

Because clinical data on the use of dorzolamide ophthalmic solution in children are limited, the use of this medication in pediatric patients is not recommended.

Overdose

Limited data are available regarding overdose due to accidental or intentional ingestion of dorzolamide hydrochloride drops.

Symptoms: Following oral ingestion, somnolence, nausea, dizziness, headache, weakness, night terrors, and dysphagia have been reported.

Treatment: Symptomatic and supportive. Possible disturbances in electrolyte balance, development of acidosis, and central nervous system (CNS) effects may occur. Monitoring of serum electrolytes (particularly potassium) and blood pH is recommended.

Adverse Reactions

During clinical trials, the most commonly reported adverse reactions were ocular pain and eye irritation, occurring in approximately 1–2% of patients.

The adverse reactions listed below are classified by frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data). Within each category, adverse reactions are listed in order of decreasing severity.

Nervous system disorders:

Common – headache;
Rare – paraesthesia, dizziness.

Eye disorders:

Very common – burning and stinging;
Common – superficial punctate keratitis, lacrimation, conjunctivitis, blepharitis, eye pruritus, eye irritation, blurred vision;
Uncommon – iritis;
Rare – ocular irritation including hyperaemia, pain, eyelid adhesion, transient myopia (resolving after discontinuation of treatment), corneal edema, ocular hypotony, choroidal detachment following filtration procedures;
Frequency not known – sensation of foreign body in the eye.

Cardiac disorders:

Frequency not known – palpitations, tachycardia.

Vascular disorders:

Frequency not known – hypertension.

Respiratory system disorders:

Rare – epistaxis;
Frequency not known – dyspnoea.

Gastrointestinal disorders:

Common – nausea, bitter taste;
Rare – throat irritation, dry mouth.

Skin and subcutaneous tissue disorders:

Rare – contact dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Renal and urinary disorders:

Rare – nephrolithiasis.

General disorders and administration site conditions:

Common – asthenia/fatigue;
Rare – hypersensitivity, local reactions (subjective and objective), including reactions involving the eyelids, and manifestations of systemic allergic reactions, including angioedema, bronchospasm, urticaria, pruritus, rash, dyspnoea.

Investigations:

No significant electrolyte disturbances related to dorzolamide use have been reported.

Reporting of suspected adverse reactions after marketing authorization is of great importance. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 24 months. After opening, store for no more than 4 weeks.

Storage conditions. Store below 25°C in a place inaccessible to children.

Packaging.

5 ml in a dropper bottle; 1 dropper bottle in a cardboard box.

Prescription category. Prescription only.

Manufacturer. Micro Labs Limited.

Manufacturer's address and location of operations.

Plot No. 113-116, Phase IV, KIADB, Bommasandra Industrial Area, Jigani Link Road, Anekal Taluk, Bangalore 560 099, India.