Fleoptic

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLEOPTIK® (FLEOPTIK)

Composition:

Active substance: levofloxacin;

1 ml of eye drops contains 5 mg of levofloxacin as levofloxacin hemihydrate;

Excipients: sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear solution, from pale yellow to pale greenish-yellow in color, practically free from visible mechanical particles.

Pharmacotherapeutic group. Medicinal products used in ophthalmology. Antimicrobial agents. Fluoroquinolones. Levofloxacin.

ATC code S01AE05.

Pharmacological properties.

Pharmacodynamics.

Levofloxacin is the L-isomer of the racemic drug substance ofloxacin. The antibacterial activity is primarily attributed to the L-isomer of ofloxacin.

Mechanism of action.

Levofloxacin is a fluoroquinolone antibacterial agent that inhibits the activity of bacterial type II topoisomerases—DNA gyrase and topoisomerase IV. The action of levofloxacin in Gram-negative bacteria is primarily directed against DNA gyrase, whereas in Gram-positive bacteria it targets topoisomerase IV.

Mechanisms of resistance development.

There are two main mechanisms of bacterial resistance to levofloxacin: reduced intracellular concentration of the drug or alterations in the target enzymes against which the drug acts. These changes arise due to mutations in chromosomal genes encoding DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE; grlA and grlB in Staphylococcus aureus). Causes of resistance due to reduced intracellular drug concentration include alterations in outer membrane porins (OmpF), which reduce the penetration of fluoroquinolones into Gram-negative bacteria, or efflux pumps that promote drug expulsion. Efflux-mediated resistance has been described in pneumococci (PmrA), staphylococci (NorA), and anaerobic and Gram-negative bacteria. Additionally, plasmid-mediated resistance to quinolones (determined by the qnr gene) has been reported in Klebsiella pneumoniae and E. coli.

Cross-resistance.

Cross-resistance among fluoroquinolones may occur. A single mutation does not usually lead to clinical resistance; however, multiple mutations typically result in clinical resistance to all agents within the fluoroquinolone class. Alterations in outer membrane porins and efflux systems may have broad substrate specificity, affecting multiple classes of antibacterial agents and leading to multidrug resistance.

Breakpoints.

The MIC (minimum inhibitory concentration) breakpoints that distinguish susceptible and moderately resistant organisms from resistant ones according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) are as follows:

Pseudomonas spp., Staphylococcus spp., Streptococcus A, B, C, G:
susceptible ≤ 1 mg/L, resistant > 2 mg/L;

Streptococcus pneumoniae: susceptible ≤ 2 mg/L, resistant > 2 mg/L;

Haemophilus influenzae, Moraxella catarrhalis: susceptible ≤ 1 mg/L, resistant > 1 mg/L.

All other pathogenic microorganisms: susceptible ≤ 1 mg/L, resistant > 2 mg/L.

Antibacterial spectrum.

The prevalence of acquired resistance in specific microorganisms may vary geographically and over time; therefore, local resistance data should be consulted, especially when treating severe infections. Thus, the information provided below offers only approximate guidance and recommendations regarding possible susceptibility or lack thereof to levofloxacin. Expert consultation should be sought if local resistance prevalence raises concerns about the appropriateness of using the medicinal product against at least some types of infections.

The table below includes only bacterial species commonly associated with external ocular infections such as conjunctivitis.

Antibacterial spectrum: susceptibility categories and resistance characteristics according to EUCAST requirements.

* MSSA – *Staphylococcus aure游戏副本

Clinical characteristics.

Indications.

Topical treatment for patients aged 1 year and older with external bacterial ocular infections caused by microorganisms sensitive to levofloxacin.

Contraindications.

Hypersensitivity to the active substance levofloxacin, increased sensitivity to other quinolones, or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

No specific studies have been conducted on the interaction of this drug with other medications.

Since maximum plasma concentrations of levofloxacin after ocular instillation are at least 1000 times lower than those observed after standard oral doses, interactions reported for systemic administration are unlikely to be clinically significant when using levofloxacin ophthalmic drops.

Paediatric population.

Drug interaction studies have not been performed.

Special precautions for use

The medicinal product must not be administered under the conjunctiva. The solution should not be injected directly into the anterior chamber of the eye.

As with other antimicrobial medicinal products, prolonged use may result in overgrowth of non-susceptible microorganisms, including fungi. If the patient's condition worsens due to infection or if there is no clinical improvement within an appropriate period of time, the drug should be discontinued and alternative therapy initiated.

When clinically indicated, patients should be examined using magnification techniques, such as slit-lamp biomicroscopy, and, if necessary, fluorescein staining.

Administration of systemic fluoroquinolones has been associated with hypersensitivity reactions, even after a single dose. If an allergic reaction to levofloxacin occurs, the drug should be discontinued.

With systemic fluoroquinolone therapy, including levofloxacin, tendon inflammation and tendon rupture may occur, particularly in elderly patients receiving concomitant corticosteroids. Therefore, caution is required and levofloxacin ophthalmic drops should be discontinued at the first signs of tendon inflammation.

Patients with bacterial external ocular infections should not wear contact lenses.

Use during pregnancy or breastfeeding

Pregnancy. There are insufficient data on the use of levofloxacin in pregnant women. Animal studies do not indicate any direct or indirect harmful effects on reproductive function. The potential risk for humans is unknown. FLEOPTIC® eye drops should be prescribed during pregnancy only if the expected benefit to the pregnant woman outweighs the potential risk to the fetus.

Breastfeeding. Levofloxacin passes into breast milk. However, no effects on the breastfed infant are expected with therapeutic doses of FLEOPTIC®. FLEOPTIC® eye drops should be used during breastfeeding only if the expected benefit to the mother justifies the potential risk to the infant.

Fertility. Levofloxacin did not impair fertility in rats at exposures significantly exceeding the maximum human exposure following ophthalmic administration.

Ability to affect reaction speed while driving or operating machinery

Levofloxacin ophthalmic drops have negligible influence on the ability to drive or operate machinery.

If any transient effect on vision occurs, patients should wait until vision clears before driving or operating machinery.

Dosage and Administration.

For ophthalmic use.

1−2 drops into the affected eye(s) every 2 hours up to 8 times daily, immediately after awakening, during the first 2 days, then 4 times daily from day 3 to day 5.

When using different local ophthalmic medicinal products concomitantly, an interval of at least 15 minutes should be maintained between administrations.

To prevent contamination of the dropper tip and solution, the tip must not touch the eyelids or areas around the eye.

The duration of treatment depends on the severity of the disorder as well as the clinical and bacteriological course of the disease. The usual duration of treatment is 5 days.

The safety and efficacy of treatment for corneal ulceration and ophthalmia neonatorum have not been established.

Due to lack of safety and efficacy data, levofloxacin ophthalmic drops are not recommended for use in patients under 1 year of age.

Use in elderly patients.

There is no need to adjust the dose for elderly patients.

Children.

The doses of the drug used in adults and children aged 1 year and older are similar.

The safety and efficacy of levofloxacin ophthalmic drops in children aged 1 year and older have been established.

The safety and efficacy of levofloxacin ophthalmic drops in children under 1 year of age have not been established. There are no adequate data available.

Overdose.

The total amount of levofloxacin in the ophthalmic drop bottle is too small to cause toxic effects following accidental oral ingestion. If necessary, the patient should be clinically monitored and supportive measures applied. In case of local overdose, the eyes should be irrigated with clean, room-temperature water.

Pediatric patients.

Management in case of overdose is the same for adults and children aged 1 year and older.

Adverse reactions.

Adverse reactions can be expected in approximately 10% of patients. These reactions are usually mild or moderate and transient, primarily limited to the eye area.

Listed below are adverse reactions identified as definitely, probably, or possibly related to treatment, reported during clinical trials and post-marketing use.

Criteria for assessing the frequency of adverse reactions: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

Immune system disorders:
Rare – extracocular allergic reactions, including skin rash; very rare – anaphylaxis.

Nervous system disorders:
Uncommon – headache.

Eye disorders:
Common – burning sensation in eyes, blurred vision, and mucus strands; uncommon – eyelid crusting, chemosis, conjunctival papillary reaction, eyelid edema, eye discomfort, foreign body sensation, eye itching, eye pain, conjunctival infection, conjunctival follicles, dry eyes, eyelid erythema, and photophobia.

Corneal deposits were not observed during clinical trials.

Respiratory, thoracic and mediastinal disorders:
Uncommon – rhinitis; very rare – laryngeal edema.

Additional adverse reactions observed with systemic administration of the active substance (levofloxacin) and which may potentially occur during use of this medicinal product.

Tendon ruptures of the shoulder, hand, Achilles tendon, and other tendons requiring surgical intervention or resulting in prolonged disability have been reported in patients receiving systemic fluoroquinolones. Post-marketing studies and experience with systemic quinolones have shown that the risk of tendon rupture may be increased in patients receiving corticosteroids, particularly in elderly patients and in tendons under high stress, including the Achilles tendon.

Paediatric population.

The frequency, type, and severity of adverse reactions in children are expected to be similar to those in adults.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua

Shelf life. 3 years.

After opening the bottle, store the eye drops in the carton to protect from light. Use within 4 weeks.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging.

5 ml in a bottle, 1 bottle in a carton.

Prescription status.

Prescription only.

Manufacturer.

JSC "KYIV VITAMIN PLANT" (manufactured from bulk product by Raffarm S.A., Greece).

Manufacturer's address and location of operations.

38, Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua