L-Dexopt (Drops) Instructions for Use

Marketing Authorization Holder

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

S01CA01 (Dexamethasone and antimicrobial drugs)

Active Substances

Dexamethasone (Rec.INN registered by WHO)

Levofloxacin (Rec.INN registered by WHO)

Dosage Form

L-Dexopt

Eye drops 1 mg+5 mg/1 ml: bottle 5 ml with a dropper cap

Dosage Form, Packaging, and Composition

Eye drops in the form of a clear solution from light yellow to light yellow with a greenish tint.

Excipients: polysorbate 80 – 0.5 mg, creatinine – 2 mg, sodium citrate – 2.85 mg, disodium edetate – 0.5 mg, sodium metabisulfite – 1 mg, sodium chloride – 6.2 mg, benzalkonium chloride – 0.05 mg, 1M hydrochloric acid solution or 1M sodium hydroxide solution – to pH 7.4±0.1, purified water – to 1 ml (1009.3 mg).

5 ml – low-density polyethylene bottles (1) with a dropper cap – cardboard packs.

Clinical-Pharmacological Group

Topical corticosteroids for ophthalmology

Pharmacotherapeutic Group

Combined anti-inflammatory and antimicrobial agent for topical use (glucocorticosteroid + antimicrobial agent – fluoroquinolone)

Pharmacological Action

A combined medicinal product for topical use in ophthalmology.

Dexamethasone is a synthetic fluorinated glucocorticosteroid that does not possess mineralocorticoid activity. It exerts anti-inflammatory, anti-allergic, and desensitizing effects. Dexamethasone actively suppresses inflammatory processes by inhibiting the release of inflammatory mediators by eosinophils, the migration of mast cells, and by reducing capillary permeability and vasodilation. With topical application, instillation into the eye, dexamethasone may exert systemic effects only in doses significantly exceeding the recommended ones.

Levofloxacin is a synthetic broad-spectrum antibacterial agent from the fluoroquinolone group, the levorotatory isomer of ofloxacin. It blocks DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of microbial cells.

Levofloxacin is active against most strains of microorganisms in vitro and in vivo.

Susceptible microorganisms: aerobic gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-susceptible/intermediately susceptible strains), Staphylococcus aureus (methicillin-susceptible strains), Staphylococcus epidermidis (methicillin-susceptible strains), Staphylococcus spp. (leukotoxin-containing); Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-susceptible/intermediately susceptible/resistant strains), Streptococcus pyogenes, Streptococcus spp. viridans group (penicillin-susceptible/resistant strains) aerobic gram-negative microorganisms: Acinetobacter spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-susceptible/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (beta-lactamase-producing and non-producing strains), Morganella morganii, Neisseria gonorrhoeae (penicillinase-producing and non-producing strains), Neisseria meningitidis, Pasteurella spp. (including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (hospital infections caused by Pseudomonas aeruginosa may require combination therapy), Serratia spp. (including Serratia marcescens), Salmonella spp.; anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veillonella spp.; other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella spp. (including Legionella pneumophila), Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately susceptible microorganisms: aerobic gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains); aerobic gram-negative microorganisms: Campylobacter jejuni, Campylobacter coli; anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Resistant microorganisms: aerobic gram-positive microorganisms – Staphylococcus aureus (methicillin-resistant strains), other Staphylococcus spp. (coagulase-negative methicillin-resistant strains); aerobic gram-negative microorganisms – Alcaligenes xylosoxidans; anaerobic microorganisms – Bacteroides thetaiotaomicron; other microorganisms – Mycobacterium avium.

Resistance to levofloxacin develops as a result of a stepwise process of mutations in the genes encoding both type II topoisomerases: DNA gyrase and topoisomerase IV. Other resistance mechanisms, such as the mechanism affecting microbial cell penetration barriers (a mechanism characteristic of Pseudomonas aeruginosa) and the efflux mechanism (active removal of the antimicrobial agent from the microbial cell), can also reduce the susceptibility of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action of levofloxacin, cross-resistance between levofloxacin and other antimicrobial agents is usually not observed.

Pharmacokinetics

Dexamethasone

After instillation into the eye, dexamethasone penetrates well into the aqueous humor, corneal epithelium, ciliary body, retina, iris, and choroid. With inflammation or damage to the mucous membrane, the penetration rate increases. With topical application, instillation into the eye, dexamethasone is detected in the intraocular fluid after 30 minutes, C_max is reached after 90-120 minutes, the average concentration is 31 ng/ml. After 12 hours, a low but detectable concentration is noted in the intraocular fluid. The bioavailability of dexamethasone with oral administration in healthy individuals and patients varies from 70% to 80%.

Levofloxacin

After instillation into the eye, levofloxacin is well retained in the tear film. The concentration of levofloxacin in the tear fluid after a single dose (1 drop) quickly reaches high values and is maintained at a level above the minimum inhibitory concentration for most susceptible ocular pathogens (less than or equal to 2 µg/ml) for at least 6 hours. Studies in healthy volunteers have shown that the average concentrations of levofloxacin in the tear film, measured 4 and 6 hours after topical application, were 17 µg/ml and 6.6 µg/ml, respectively. In 5 out of 6 volunteers, levofloxacin concentrations were 2 µg/ml and above 4 hours after instillation. In 4 out of 6 volunteers, this concentration persisted 6 hours after instillation. The average concentration of levofloxacin in blood plasma 1 hour after application is from 0.86 ng/ml on day 1 to 2.05 ng/ml. C_max of levofloxacin in plasma, equal to 2.25 ng/ml, was detected on day 4 after two days of application every 2 hours up to 8 times a day. C_max of levofloxacin, achieved on day 15 with instillation into the eye, is more than 1000 times lower than those concentrations observed after oral administration of levofloxacin in standard doses.

Indications

Treatment of superficial bacterial infections of the eye caused by microorganisms susceptible to levofloxacin.

Prevention and treatment of inflammatory phenomena in the postoperative period after cataract extraction.

ICD codes

Dosage Regimen

A single dose is 1-2 drops into the conjunctival sac of the affected eye.

The frequency of application depends on the indications and treatment regimen.

The duration of the course of treatment is determined by the severity of the condition, including the outcome of the surgery performed, and is determined by the doctor based on the clinical picture and biomicroscopy data. After completing one week of therapy, it is recommended to re-evaluate the patient’s condition to determine the need to continue local therapy with a drug containing a glucocorticosteroid. For eye drops containing dexamethasone, the total duration of treatment should not exceed 14 days. Therapy should be completed gradually.

Adverse Reactions

From the organ of vision often – eye burning, eye discomfort; infrequently – lacrimation, dry eye sensation, keratitis, conjunctivitis, dry eye syndrome, corneal staining with medical dye, photophobia, blurred vision, itching, increased lacrimation, foreign body sensation or unusual sensations in the eye, crusting on the edges of the eyelids, eye irritation, eye hyperemia, glaucoma, ulcerative keratitis, increased intraocular pressure, decreased visual acuity, corneal erosion, eyelid ptosis, eye pain, mydriasis.

From the liver and biliary tract infrequently – increased activity of ALT, AST, ALP.

From the nervous system infrequently – dysgeusia; frequency unknown – dizziness, headache.

From the respiratory system infrequently – rhinitis.

Contraindications

Hypersensitivity to levofloxacin and dexamethasone; dendritic keratitis; chickenpox and other viral diseases of the cornea and conjunctiva; vaccination; mycobacterial eye infections; acute purulent eye diseases without concomitant antimicrobial therapy; fungal eye diseases or previously untreated parasitic eye infections; violation of the integrity of the corneal epithelium, including after removal of a foreign body; pregnancy, breastfeeding period; age under 18 years.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

Long-term use of topical glucocorticosteroids can lead to increased intraocular pressure and/or glaucoma with damage to the optic nerve, decreased visual acuity and visual field defects, and the formation of posterior subcapsular cataracts. The risk of increased intraocular pressure and/or cataract formation due to glucocorticosteroid use is higher in predisposed patients (for example, with diabetes mellitus). The risk of increased intraocular pressure increases in patients with concomitant ocular hypertension and/or glaucoma, as well as in patients with a family history of glaucoma.

In predisposed patients, including patients receiving treatment with CYP3A4 inhibitors (including ritonavir and cobicistat), after intensive therapy or continuous long-term therapy, Cushing’s syndrome and/or adrenal suppression may occur due to systemic absorption of dexamethasone for ophthalmic use. In such cases, the drug should be discontinued not immediately, but gradually.

Glucocorticosteroids can reduce resistance to bacterial, viral, fungal, or parasitic infections and promote their development, as well as mask the clinical signs of infection.

The appearance of non-healing ulcers on the cornea may indicate the development of fungal invasion. If fungal invasion occurs, glucocorticosteroid therapy must be discontinued.

Glucocorticosteroids with topical application can slow down the process of corneal healing. It is known that topical NSAIDs also slow down or delay healing. The simultaneous use of topical NSAIDs and topical glucocorticosteroids may increase the likelihood of healing disorders.

It is known that in diseases that cause thinning of the cornea or sclera, perforations may occur as a result of the use of topical glucocorticosteroids.

If a patient develops symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist to identify possible causes of their development, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy, which have been reported after the use of systemic and topical glucocorticosteroids.

Topical glucocorticosteroids should not be used until the etiology of the eye lesion is established.

Systemic use of fluoroquinolones can lead to a hypersensitivity reaction even after a single dose. If an allergic reaction to levofloxacin occurs, the use of this combination should be discontinued.

There is no information on the efficacy and safety of levofloxacin use in the therapy of corneal ulcers. In clinical studies, no formation of precipitates on the cornea was noted.

Long-term use of this combination may lead to the development of antibiotic resistance as a result of overgrowth of resistant microorganisms, including fungi. If an infection develops, this agent should be discontinued and therapy with other drugs should be prescribed. If there are clinical indications, the patient should be examined using additional means, such as slit-lamp biomicroscopy, and, if necessary, fluorescein staining.

The use of contact lenses is not recommended during the treatment of infectious or inflammatory eye diseases.

During cataract extraction surgery, contact lenses cannot be used throughout the entire period of drug application.

Effect on the ability to drive vehicles and operate machinery

Immediately after instillation, temporary blurred vision is possible. It is not recommended to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions until clarity of vision is restored.

Drug Interactions

Simultaneous use in ophthalmology of topical glucocorticosteroids and topical NSAIDs may increase the likelihood of corneal healing disorders.

The risk of additional intraocular pressure increase cannot be excluded if dexamethasone is used concomitantly with anticholinergic agents, which can also cause an increase in intraocular pressure in predisposed patients. In case of concomitant use with antiglaucoma drugs, a decrease in the hypotensive effect of the latter is possible.

CYP3A4 inhibitors, including ritonavir and cobicistat, can increase the level of systemic exposure, leading to an increased risk of adrenal suppression/Cushing’s syndrome. The combination of these drugs should be avoided, except in cases where the beneficial effect outweighs the increased risk of systemic side effects of glucocorticosteroids, but in this case, the patient should be closely monitored for the development of such systemic effects.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.