Floxanext

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

Composition:

Active substance: ofloxacin;

1 ml of solution contains 3.0 mg of ofloxacin;

Excipients: benzalkonium chloride solution, sodium chloride, sodium hydroxide or hydrochloric acid (if necessary), water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear, slightly yellowish solution, practically free from particles.

Pharmacotherapeutic group. Medicinal products used in ophthalmology. Antibacterial agents. ATC code S01AE01.

Pharmacological Properties

Pharmacodynamics

Ofloxacin is a bactericidal synthetic chemotherapeutic agent belonging to the group of fluoroquinolones. Ofloxacin exhibits high activity against a broad spectrum of gram-negative microorganisms and a smaller number of gram-positive microorganisms. Ofloxacin has demonstrated high activity against most strains of these microorganisms in vitro and in clinical practice in the treatment of ocular infections. Data on clinical efficacy of ofloxacin against Streptococcus pneumoniae are based on a limited number of isolates only. In bacterial cells, ofloxacin inhibits DNA gyrase—an enzyme essential for bacterial DNA replication and transcription.

Ofloxacin is active against the following gram-negative microorganisms: Acinetobacter calcoaceticus; Enterobacter species, including E. cloacae; Haemophilis species, including H. influenzae and H. aegyptius; Klebsiella species, including K. pneumoniae; Moraxella species; Morganella morganii; Proteus species, including P. mirabilis; Pseudomonas species, including P. aeruginosa, P. cepacia, P. fluorescens; Serratia species, including S. marcescens.

Ofloxacin is active against the following gram-positive microorganisms: Bacillus species, Corynebacterium, Micrococcus, Staphylococcus, including S. aureus and S. epidermidis, Streptococcus, including S. pneumoniae (see above), S. viridans, and S. beta-haemolyticus.

Ofloxacin is not susceptible to degradation by beta-lactamase enzymes and is not modified by chloramphenicol acetyltransferase, aminoglycoside adenyltransferase, or aminoglycoside phosphotransferase enzymes.

Pharmacokinetics

After ocular instillation, ofloxacin penetrates well into the tear film. The mean concentration of ofloxacin in tears measured 4 hours after administration (9.2 µg/g) was higher than the minimum concentration required to inhibit 90% of most strains causing ocular infections (MIC90) in vitro, which was 2 µg/g.

The maximum concentration of ofloxacin in blood serum after 10 days of topical ophthalmic administration was 1000 times lower than the concentration achieved after a standard oral dose of ofloxacin. There have been no reports of systemic adverse reactions following topical ophthalmic use of ofloxacin.

Clinical characteristics.

Indications.

Topical treatment of external ocular infections (such as conjunctivitis and keratitis) in adults and children, caused by microorganisms sensitive to ofloxacin.

Official guidelines on the appropriate use of antibacterial agents should be taken into account.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

When certain quinolones are administered systemically, clearance of caffeine and theophylline metabolites is inhibited. Drug interaction studies conducted with systemic administration of ofloxacin have shown that clearance of caffeine and theophylline metabolites is only slightly affected by ofloxacin.

There have also been reports of increased frequency of CNS toxicity following systemic administration of fluoroquinolones together with nonsteroidal anti-inflammatory drugs (NSAIDs). However, such reports have not been observed with concomitant systemic use of NSAIDs and ofloxacin.

FloxANext, like other fluoroquinolones, should be used with caution in patients receiving medicinal products that prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

Special precautions for use.

Floxanext is not intended for injection use.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic/anaphylactoid reactions) have been reported, some occurring after the first dose in patients receiving systemic quinolones, including ofloxacin. Some of these reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal, or facial swelling), airway obstruction, dyspnea, urticaria, and pruritus.

If an allergic reaction to Floxanext occurs, administration of the drug should be discontinued. The drug should be used with caution in patients who have previously shown hypersensitivity to other antibacterial agents of the quinolone group.

When using Floxanext, the risk of exposure to the nasopharynx should be considered, as this may promote the development and spread of bacterial resistance. As with other anti-infective agents, prolonged use may lead to overgrowth of non-susceptible microorganisms.

If infection worsens or no clinical improvement is observed within a rational and justified period, treatment with the drug should be discontinued and alternative therapy initiated.

In patients using ofloxacin as ophthalmic drops for local application, Stevens-Johnson syndrome has been reported; however, a causal relationship has not been established.

Cardiac disorders

Fluoroquinolones, including Floxanext, should be used with caution in patients with known risk factors for QT interval prolongation, such as:

• congenital long QT syndrome;
• concomitant use of medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
• uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
• cardiac diseases (e.g., heart failure, myocardial infarction, bradycardia).

Elderly patients and younger women may be more sensitive to drugs that prolong the QT interval. Therefore, Floxanext should be used with caution in these patient groups.

Children

Safety and efficacy in children under 1 year of age have not been established.

Data on the efficacy and safety of Floxanext 0.3% ophthalmic drops for the treatment of neonatal conjunctivitis are very limited.

Floxanext 0.3% ophthalmic drops are not recommended for the treatment of neonatal ophthalmia caused by Neisseria gonorrhoeae or Chlamydia trachomatis, as its use in these patients has not been evaluated.

Tendinitis (inflammation of tendons) and tendon rupture may occur during therapy with systemic fluoroquinolones, including ofloxacin, particularly in elderly patients and in patients concurrently receiving corticosteroids. Therefore, such patients should be closely monitored, and treatment should be discontinued at the first signs of tendinitis (see section "Adverse reactions").

Use in elderly patients

There are no comparative data on the local use of the drug in elderly patients compared to other age groups.

Clinical and preclinical publications have reported cases of corneal perforation in patients with pre-existing corneal epithelial defects or corneal ulcers treated with topically applied fluoroquinolones. However, many of these reports involved significant concomitant factors, including advanced age, presence of large ulcers, concomitant ocular conditions (e.g., severe dry eye), systemic inflammatory diseases (e.g., rheumatoid arthritis), and concomitant use of ophthalmic steroids or NSAIDs. Nevertheless, the drug should be used with caution in patients with corneal epithelial defects or corneal ulcers due to the risk of corneal perforation.

During treatment with ophthalmic formulations of ofloxacin, corneal deposits have been reported; however, a causal relationship has not been established.

Prolonged administration of other fluoroquinolones at high doses in experimental animals has led to lens opacities. However, this effect has not been reported in humans receiving the drug, nor has it been observed after topical application of ofloxacin for up to six months in animal studies.

During treatment with ofloxacin, exposure to direct sunlight and ultraviolet radiation should be avoided due to the potential for photosensitization.

Floxanext contains the preservative benzalkonium chloride, which may cause eye irritation and may discolor soft contact lenses.

Contact lenses should not be worn during treatment.

When using Floxanext ophthalmic drops together with other ophthalmic drops/ointments, medicinal products should be administered at least 15 minutes apart. In any case, ophthalmic ointment should be applied last.

Use during pregnancy or breastfeeding.

Pregnancy.

Adequate and well-controlled studies on the use of Floxanext in pregnant women have not been conducted. Since systemic fluoroquinolones can cause arthropathy in immature animals, the drug should not be used during pregnancy.

Breastfeeding.

Since ofloxacin and other systemically administered quinolones are excreted in breast milk and there is potential for harm to the infant, a decision should be made whether to discontinue breastfeeding temporarily, taking into account the importance of the drug to the mother.

Fertility.

Ofloxacin had no effect on fertility in animals.

Ability to affect reaction speed when driving or operating machinery.

No studies on the effect on the ability to drive or operate machinery have been conducted.

Transient blurred vision may occur after instillation of ophthalmic drops. Patients should not drive or operate hazardous machinery until vision is restored.

Dosage and Administration.

The medication is intended for topical ocular use only.

During the first 2 days, instill 1–2 drops every 2–4 hours, then reduce to 4 times daily. The duration of treatment should not exceed 10 days.

Children.

The safety and efficacy of the medication in children under 1 year of age have not been established.

Overdose.

In case of overdose, symptomatic treatment should be administered. As QT interval prolongation may occur, ECG monitoring is recommended.

Adverse reactions.

General manifestations.

Serious reactions following systemic administration of ofloxacin are rare, and most symptoms are reversible. Since a small amount of ofloxacin is systemically absorbed after topical application, adverse effects associated with systemic use of the drug may occur.

The following categories are used to classify 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.

Frequency not known: hypersensitivity reactions, including manifestations and symptoms of allergy (e.g., eye and eyelid itching) and anaphylactic reactions (e.g., angioneurotic edema, dyspnea, anaphylactic shock, oropharyngeal edema, facial and tongue swelling).

Nervous system disorders.

Frequency not known: dizziness.

Eye disorders.

Common: eye irritation, ocular discomfort.

Frequency not known: keratitis, conjunctivitis, blurred vision, photophobia, eye swelling, foreign body sensation, increased lacrimation, dry eye, eye pain, ocular hyperemia, periorbital edema (including eyelid swelling).

Cardiovascular system disorders.

Frequency not known: ventricular arrhythmia and torsades de pointes (reported primarily in patients with risk factors for QT interval prolongation), QT interval prolongation on ECG.

Gastrointestinal disorders.

Frequency not known: nausea.

Skin and subcutaneous tissue disorders.

Frequency not known: Stevens-Johnson syndrome, toxic epidermal necrolysis.

In patients receiving systemic fluoroquinolone therapy, tendon ruptures of the shoulder, hand, Achilles tendon, or other tendons have been reported, requiring surgical intervention or resulting in prolonged disability. Clinical studies and post-marketing experience with systemic quinolones indicate that the risk of such tendon ruptures may be increased in patients concurrently receiving corticosteroids, particularly in elderly patients and in cases of significant tendon stress, including the Achilles tendon (see section "Special precautions").

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

Shelf life of the unopened vial:

30 months.

Vial after first opening:

After first opening, the contents of the dropper vial should be used within 4 weeks; after this period, any remaining product should be disposed of.

Storage conditions.

The medicinal product does not require special storage temperature conditions.

Store in the original packaging in a place protected from light.

Keep out of reach of children.

Packaging. 10 ml in a dropper vial. 1 dropper vial per carton.

Prescription status.

Prescription only.

Manufacturer.

FARMIGEA S.P.A./FARMIGEA S.P.A.

Manufacturer's address and location of its business operations.

Via G.B. Oliva, 8 - 56121 Pisa (PI), Italy /Via G.B. Oliva, 8 - 56121 Pisa (PI), Italy.