L-Optic Rompharm (Drops) Instructions for Use

Marketing Authorization Holder

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

ATC Code

S01AE05 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN registered by WHO)

Dosage Form

L-Optic Rompharm

Eye drops 5 mg/1 ml: 5 ml bottle with 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: sodium chloride – 8.75 mg, benzalkonium chloride – 0.05 mg, hydrochloric acid solution 1M or sodium hydroxide solution 1M – to adjust pH to 6.5±0.05, purified water – up to 1 ml.

5 ml – polyethylene bottles (1) with dropper cap – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group for topical use in ophthalmology

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

A synthetic broad-spectrum antibacterial drug 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-acquired 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 the penetration barriers of the microbial cell (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

After instillation into the eye, Levofloxacin is well retained in the tear film. Studies in healthy volunteers have shown that the mean 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 five out of six volunteers, levofloxacin concentrations were 2 µg/ml and above 4 hours after instillation. In four out of six volunteers, this concentration persisted 6 hours after instillation.

The mean concentration of levofloxacin when using eye drops in the aqueous humor is statistically significantly higher than the mean concentration of ofloxacin (p=0.0008). In fact, it is approximately twice as high as the mean concentration of ofloxacin (1139.9±717.1 ng/ml and 621.7±368.7 ng/ml, respectively).

The mean plasma concentration of levofloxacin 1 hour after application ranges from 0.86 ng/ml on the first day to 2.05 ng/ml. The C_max of levofloxacin in plasma, equal to 2.25 ng/ml, was detected on the 4th day after two days of using the drug every 2 hours up to 8 times/day. The C_max of levofloxacin reached on the 15th day is more than 1000 times lower than those concentrations observed after oral administration of standard doses of levofloxacin.

Indications

Treatment of superficial bacterial eye infections caused by susceptible microorganisms in adults and children over 1 year of age; prevention of complications after surgical and laser eye operations.

When using a drug containing Levofloxacin, official national recommendations for the appropriate use of antibacterial drugs, as well as the susceptibility of pathogenic microorganisms in a particular country, should be taken into account.

ICD codes

Dosage Regimen

For acute bacterial conjunctivitis in adults and children over 1 year, instill one to two drops into the affected eye(s) every two hours while awake, up to eight times daily on days one and two.

On days three through seven, reduce frequency to one to two drops into the affected eye(s) every four hours while awake, up to four times daily.

For corneal ulcers caused by susceptible organisms, instill one to two drops into the affected eye every 30 minutes while awake and every four to six hours after retiring, on days one and two.

From day three until completion of therapy, instill one to two drops into the affected eye hourly while awake.

On days six through nine, further reduce frequency to one to two drops into the affected eye every four hours while awake.

For surgical prophylaxis, instill one to two drops into the eye to be operated on, one to four times daily, beginning 1-2 days before surgery.

On the day of surgery, administer one to two drops every 30 to 120 minutes prior to the procedure.

Postoperatively, continue one to two dropsfour times daily for up to seven days or as directed.

The average treatment duration is five days, but adjust based on severity and clinical response.

If using multiple topical ophthalmic agents, maintain an interval of at least 15 minutes between instillations.

Do not allow the dropper tip to contact any surface to avoid contamination of the solution.

Adverse Reactions

Immune system disorders rarely – systemic allergic reactions, including skin rash; very rarely – anaphylactic shock.

Nervous system disorders uncommon – headache.

Eye disorders common – eye burning, decreased vision, filamentous mucous discharge in the conjunctival cavity; uncommon – chemosis, conjunctival injection, papillary conjunctivitis, eyelid edema, eyelid erythema, eye discomfort, eye itching, eye pain, dry eye syndrome, photophobia.

Respiratory system disorders uncommon – rhinitis, very rarely – laryngeal edema.

Contraindications

Children under 1 year of age; hypersensitivity to levofloxacin and other quinolones.

Use in Pregnancy and Lactation

Levofloxacin eye drops can be used during pregnancy if the potential benefit to the mother outweighs the possible risk to the fetus.

Levofloxacin is excreted in breast milk. However, exposure to the breastfed infant is not expected when levofloxacin is used at therapeutic doses. Levofloxacin eye drops can be used during breastfeeding if the potential benefit to the mother outweighs any possible risk to the breastfed infant.

Pediatric Use

Contraindicated in children under 1 year of age.

Special Precautions

If allergic reactions occur during treatment with levofloxacin, it is necessary to immediately discontinue the use of the drug.

With prolonged treatment with levofloxacin (as with other antibiotics), overgrowth of non-susceptible microorganisms, including fungal flora, is possible.

In case of worsening of the disease or lack of improvement with the use of the drug, it is necessary to discontinue levofloxacin therapy and switch to therapy with antibacterial drugs of other groups, with an extended ophthalmological examination, including biomicroscopy and fluorescein test.

When using several ophthalmic drugs for topical application simultaneously, a 15-minute interval between instillations must be observed.

The prevalence of acquired resistance of isolated strains of microorganisms may vary by geographic region and over time. Therefore, information on resistance to levofloxacin in a particular country is required. For the therapy of severe infections or in case of treatment failure, a microbiological diagnosis should be established with the isolation of the pathogen and determination of its susceptibility to levofloxacin.

Use in pediatrics

If use in children is necessary, a doctor’s consultation is required.

Effect on ability to drive vehicles and mechanisms

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 visual clarity is restored.

Drug Interactions

Since the C_max of levofloxacin in plasma after topical application is 1000 times less than with oral administration, interaction effects with other drugs are unlikely.

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.