Instructions Levoximed eye drops solution 5 mg/ml dropper bottle 5 ml
Composition
active ingredient: levofloxacin;
1 ml of solution contains levofloxacin (in the form of hemihydrate) 5 mg;
Excipients: sodium chloride, benzalkonium chloride, sodium hydroxide or hydrochloric acid solution, purified water.
Dosage form
Eye drops, solution.
Main physicochemical properties: transparent solution, practically free of mechanical inclusions.
Pharmacotherapeutic group
Agents used in ophthalmology. Antimicrobial agents. Fluoroquinolones. Levofloxacin. ATX code S01A E05.
Pharmacological properties
Pharmacodynamics
Levofloxacin is the L-isomer of the racemic drug substance ofloxacin. The antibacterial activity is predominantly that of 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 directed mainly at DNA gyrase, and in gram-positive bacteria - at topoisomerase IV.
Resistance.
There are two main mechanisms by which bacteria develop resistance to levofloxacin: a decrease in the concentration of levofloxacin inside the bacterial cell or a change in the set of enzymes against which it acts. Such changes occur as a result of mutations in the chromosomal genes encoding DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE; grlA and grlB in Staphylococcus aureus). Resistance due to a decrease in the concentration of levofloxacin inside the bacterial cell is due to changes in the outer membrane porins (OmpF), which reduce the ability of fluoroquinolones to penetrate into gram-negative bacteria, or to pumps that facilitate the efflux of substances. Efflux resistance has been described in pneumococci (PmrA), staphylococci (NorA), anaerobic and gram-negative bacteria. Plasma-mediated resistance to quinolones (determined by the qnr gene) has been reported in Klebsiella pneumoniae and E. coli.
Cross-resistance.
Cross-resistance between fluoroquinolones is possible. Single mutations do not result in clinical resistance, but multiple mutations usually do result in clinical resistance to all drugs in the fluoroquinolone class. Alterations in outer membrane porins and efflux systems can have broad substrate specificity, be directed against several classes of antibacterial agents, and lead to the emergence of multiple resistance.
Limit values.
The MIC (minimum inhibitory concentration) breakpoints that separate susceptible and moderately resistant organisms from resistant organisms according to the EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoint 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.
Other pathogenic microorganisms: sensitive ≤ 1 mg/l, resistant > 2 mg/l.
Spectrum of antibacterial action.
The prevalence of acquired resistance in individual species may vary geographically and over time, and it is therefore desirable to have local information on resistance, especially when treating severe infections. Therefore, the information provided provides only approximate guidance and recommendations on the possible susceptibility of microorganisms to levofloxacin. If the prevalence of resistance in a local setting is such that the use of levofloxacin against at least some types of infections is questionable, specialist advice should be sought as appropriate.
The table below only presents the types of bacteria that commonly cause external eye infections, such as conjunctivitis.
Antibacterial spectrum of action – sensitivity categories and resistance characteristics according to EUCAST requirements.
| Category I: common susceptible species | |
| Aerobic Gram-positive microorganisms | |
| Staphylococcus aureus (MSSA)* | |
| Streptococcus pneumoniae | |
| Streptococcus pyogenes | |
| Viridans group streptococci | |
| Aerobic Gram-negative microorganisms | |
| Escherichia coli | |
| Haemophilus influenzae | |
| Moraxella catarrhalis | |
| Pseudomonas aeruginosa | (Isolate from public places) |
| Other microorganisms | |
| Chlamydia trachomatis | (When treating patients with chlamydial conjunctivitis, systemic antimicrobial treatment should be administered concurrently) |
| Category II: species for which acquired resistance may pose a problem | |
| Aerobic Gram-positive microorganisms | |
| Staphylococcus aureus (MRSA)** | |
| Staphylococcus epidermidis | |
| Aerobic Gram-negative microorganisms | |
| Pseudomonas aeruginosa | (Isolate from hospitals) |
* MSSA = methicillin-susceptible Staphylococcus aureus strains.
The resistance data presented in the table are based on the results of a multicenter observational study (ophthalmology study) on the prevalence of resistance among bacterial isolates obtained from patients with eye infections in Germany, June–November 2004.
Microorganisms were classified as susceptible to levofloxacin based on in vitro susceptibility and plasma concentrations after systemic therapy. Higher peak concentrations were achieved with topical administration than with plasma. However, it is unknown whether and how the kinetics of the drug after topical ocular administration may alter the antibacterial activity of levofloxacin.
Special categories of patients.
Pediatric patients.
The pharmacodynamic properties are the same in adults and children aged 1 year and older.
Pharmacokinetics
Levofloxacin is well retained in the tear film after instillation into the eye. In a study of healthy volunteers, mean tear film concentrations of levofloxacin measured 4 and 6 hours after topical dosing were 17.0 and 6.6 μg/mL, respectively. Five of the six volunteers studied had concentrations of 2 μg/mL or greater at 4 hours post-dose. Four of the six volunteers studied had these concentrations at 6 hours post-dose.
Levofloxacin plasma concentrations were measured in 15 healthy adult volunteers at various time points during a 15-day treatment course. The mean plasma levofloxacin concentration 1 hour after dosing ranged from 0.86 ng/mL on day 1 to 2.05 ng/mL on day 15. The highest maximum levofloxacin concentration of 2.25 ng/mL was observed on day 4 after 2 days of dosing every 2 hours (total of 8 doses per day). Maximum levofloxacin concentrations increased from 0.94 ng/mL on day 1 to 2.15 ng/mL on day 15, which is 1000-fold lower than the concentrations reported after standard oral doses of levofloxacin.
The plasma concentrations of levofloxacin achieved after administration to the affected eye are unknown.
Indication
Topical treatment of external bacterial ocular infections in patients aged 1 year and older caused by microorganisms susceptible to levofloxacin.
Contraindication
Hypersensitivity to the active substance levofloxacin, other quinolones or to the excipients of the drug, such as benzalkonium chloride.
Interaction with other medicinal products and other types of interactions
No specific studies have been conducted on the interaction of levofloxacin eye drops with other drugs.
Since peak plasma concentrations of levofloxacin after instillation into the eyes are at least 1000 times lower than those observed after standard oral doses, the interactions noted for systemic use are unlikely to be clinically significant when levofloxacin eye drops are used.
Pediatric patients.
No studies have been conducted on the interaction of levofloxacin eye drops with other drugs.
Application features
The drug should not be administered under the conjunctiva and directly into the anterior chamber of the eye.
As with other anti-infectives, prolonged use of levofloxacin may result in overgrowth of non-susceptible organisms, 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 should be initiated.
According to the patient's clinical indications, an examination using magnifying devices, such as slit-lamp biomicroscopy and, if necessary, fluorescein staining, should be performed.
Patients who use contact lenses.
Patients with bacterial external eye infections should not wear contact lenses.
The medicine contains the preservative benzalkonium chloride, which may cause eye irritation.
The use of systemic fluoroquinolones has been associated with the occurrence of hypersensitivity reactions, even after a single dose. If hypersensitivity reactions develop, the drug should be discontinued.
With systemic use of fluoroquinolones, including levofloxacin, inflammation and rupture of tendons may occur, especially in elderly patients who are taking corticosteroids at the same time. Caution should be exercised when using the drug and at the first signs of tendon inflammation, its use should be discontinued.
Ability to influence reaction speed when driving vehicles or other mechanisms
Levofloxacin eye drops have a minor influence on the ability to drive or use machines.
If any temporary visual effects are observed during the use of the medicinal product, the patient should wait until the vision clears before driving or using other machinery.
Use during pregnancy or breastfeeding
There are no adequate data from the use of levofloxacin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive function. The potential risk for humans is unknown.
During pregnancy, the drug should be used only if the expected benefit to the woman justifies the potential risk to the fetus.
Breastfeeding period.
Levofloxacin passes into breast milk. However, no effects on the breastfed child are expected when using therapeutic doses of the drug. During breastfeeding, the drug should be used only if the expected benefit to the woman justifies the potential risk to the infant.
Fertility.
Levofloxacin did not impair fertility in rats at exposures significantly in excess of the maximum human exposure following ophthalmic administration.
Method of administration and doses
The medicine is intended for topical use.
The recommended dose is 1–2 drops in the affected eye(s) every 2 hours up to 8 times daily, starting immediately upon awakening for the first 2 days, then 4 times daily from days 3 to 5.
To prevent contamination of the tip of the dropper and the solution, the tip of the dropper should not come into contact with the eyelids or surrounding areas of the eye.
When using different topical ophthalmic medications simultaneously, the interval between instillations should be at least 15 minutes.
The duration of treatment depends on the severity of the disorder, as well as the clinical and bacteriological course of the disease. Usually the duration of treatment is 5 days.
The safety and effectiveness of treatment for corneal ulcers and ophthalmia neonatorum have not been established.
Due to lack of safety and efficacy data, the drug is not recommended for use in children under 1 year of age.
Elderly patients.
Such patients do not need to adjust the dosage of the drug.
Children
The doses of the drug used in adults and children over 1 year of age are similar.
The safety and efficacy of levofloxacin eye drops in children aged 1 year and older have been established.
The safety and efficacy of levofloxacin eye drops in children under 1 year of age have not yet been established. There are no relevant data.
Overdose
The total amount of levofloxacin in a bottle of eye drops is too small to cause toxic effects after accidental oral administration. If necessary, the patient should be clinically examined and supportive measures should be taken. After topical overdose, the eyes should be flushed with clean water at room temperature.
Pediatric patients.
The measures taken in case of overdose are similar in adults and children aged 1 year and over.
Adverse reactions
Adverse reactions can be expected in approximately 10% of patients. These reactions are usually mild to moderate, transient, and mainly confined to the eye area.
Since the medicinal product contains benzalkonium chloride, it may cause contact eczema and/or irritation.
The following adverse reactions, determined to be definitely, probably or possibly related to treatment, have been reported during clinical trials and post-marketing use of eye drops containing levofloxacin.
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); unknown (frequency cannot be estimated from the available data).
On the part of the immune system:
Rare: extraocular hypersensitivity reactions, including skin rash; very rare: anaphylaxis.
From the nervous system:
infrequently - headache.
On the part of the organs of vision:
often - burning in the eyes, decreased visual acuity, mucus plugging; infrequently - eyelid opacification, chemosis, conjunctival papillary reaction, eyelid edema, ocular 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 studies.
From the respiratory system, chest organs and mediastinum:
infrequently - rhinitis; very rarely - laryngeal edema.
Additional adverse reactions observed with systemic use of the active substance (levofloxacin) and which may potentially occur during the use of this medicinal product.
Tendon ruptures of the shoulder, hand, Achilles, and other tendons requiring surgical intervention or resulting in long-term disability have been reported in patients receiving systemic fluoroquinolones. Postmarketing studies and experience with systemic quinolones have suggested that there may be an increased risk of rupture in patients receiving corticosteroids, particularly in the elderly, and in tendons under heavy load, including the Achilles tendon.
Pediatric patients.
The frequency, type and severity of adverse reactions in children can be expected to be similar to those occurring in adults.
Reporting suspected adverse reactions that occur after the registration of a medicinal product is very important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.
Expiration date
3 years.
After opening the bottle, the drug can be used for 4 weeks.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging and out of the reach of children.
Packaging
5 ml in a dropper bottle, 1 dropper bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
K.O. Romfarm Company S.R.L.
Location of the manufacturer and its business address
Otopeni, Eroilor Street No. 1A, 075100, Ilfov County, Romania.
