MONAFOKS

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MОNAFOX (MONAFOX)

Composition:

Active substance: moxifloxacin;

1 ml of solution contains moxifloxacin 5 mg (in the form of moxifloxacin hydrochloride);

Excipients: boric acid, sodium chloride, sodium hydroxide 1N, water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear, greenish-yellow solution free from mechanical particles.

Pharmacotherapeutic group. Medicinal products used in ophthalmology. Antibacterials. Fluoroquinolones. ATC code S01AE07.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Moxifloxacin, a fourth-generation fluoroquinolone, inhibits DNA gyrase and topoisomerase IV, which are essential for bacterial DNA replication, repair, and recombination.

Mechanism of resistance

Resistance to fluoroquinolones, including moxifloxacin, typically arises from chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, resistance to moxifloxacin may also occur due to mutations in the mar (multidrug resistance) and qnr (quinolone resistance) gene systems. Cross-resistance with beta-lactams, macrolides, and aminoglycosides is unlikely due to differences in mechanisms of action.

Breakpoints

The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has established the following minimum inhibitory concentration (MIC) breakpoints (mg/l):

Staphylococcus species S ≤ 0.5, R > 1
Streptococcus A, B, C, G S ≤ 0.5, R > 1
Streptococcus pneumoniae S ≤ 0.5, R > 0.5
Haemophilus influenzae S ≤ 0.5, R > 0.5
Moraxella catarrhalis S ≤ 0.5, R > 0.5
Enterobacteriaceae S ≤ 0.5, R > 1
non-species-specific S ≤ 0.5, R > 1

In vitro breakpoints are used to predict the clinical efficacy of moxifloxacin when administered systemically. These breakpoints may not be applicable for topical ocular use, as higher concentrations are achieved locally and local physical/chemical conditions at the site of administration may influence drug activity.

Susceptibility

The prevalence of acquired resistance may vary geographically and over time for specific microorganisms; therefore, local information on microbial resistance patterns is desirable, especially when treating severe infections.

Expert advice should be sought if local resistance prevalence renders the activity of moxifloxacin at least questionable against certain types of infections.

Susceptible organisms

Pharmacokinetics.

When Monaflox ophthalmic solution is administered locally, systemic absorption of moxifloxacin occurs. Plasma concentrations of moxifloxacin were measured in 21 subjects following topical administration of the drug to both eyes three times daily for 4 days. Mean steady-state Cmax and AUC values were 2.7 ng/mL and 41.9 ng⁎h/mL, respectively. These values are approximately 1600 and 1200 times lower than the Cmax and AUC values observed after oral administration of moxifloxacin at the therapeutic dose of 400 mg. The plasma elimination half-life of moxifloxacin is 13 hours.

Preclinical safety data

In preclinical studies, effects following topical ocular administration were observed only at doses substantially exceeding the maximum recommended human dose, indicating limited relevance to clinical use.

Like other quinolones, moxifloxacin showed genotoxic effects in vitro in bacterial and mammalian cells. A threshold level for genotoxicity is assumed, as these effects may result from interaction with bacterial gyrase and mammalian topoisomerase II at much higher concentrations. However, in vivo studies, even at high moxifloxacin doses, showed no evidence of genotoxicity. Thus, therapeutic doses in humans provide an adequate safety margin. No signs of carcinogenic potential were observed in preclinical animal studies.

In contrast to other quinolones, moxifloxacin showed no phototoxic or photogenotoxic properties in extensive in vitro and in vivo investigations.

Clinical characteristics

Indications.

For local treatment of bacterial conjunctivitis caused by bacterial strains sensitive to moxifloxacin.

Official recommendations regarding appropriate use of antibacterial agents should be taken into account.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

No specific interaction studies have been conducted with the medicinal product Monaflox. Due to the low systemic concentration of moxifloxacin following topical ophthalmic administration, drug interaction is unlikely.

Special precautions for use.

In patients receiving systemically acting quinolone drugs, serious, and in some cases fatal, hypersensitivity reactions (anaphylactic reactions) have been reported; some occurred after the first dose of the drug. Individual reactions were accompanied by cardiovascular insufficiency, loss of consciousness, swelling (including swelling of the larynx, pharynx, or face), airway obstruction, dyspnea, pruritus, urticaria, and tinnitus.

At the first signs of allergic reactions, administration of the drug should be discontinued immediately. Acute hypersensitivity reactions to moxifloxacin or any other components of the medicinal product may require immediate emergency intervention. If clinically indicated, airway patency should be restored and oxygen therapy initiated.

As with the use of other anti-infective agents, prolonged use of moxifloxacin may result in overgrowth of non-susceptible microorganisms, including fungi. In case of superinfection, the drug should be discontinued and appropriate alternative therapy initiated.

With systemic therapy using fluoroquinolones, including moxifloxacin, tendon inflammation and tendon rupture may occur, particularly in elderly patients and in those receiving concomitant corticosteroid therapy. At the first signs of tendon inflammation, use of the medicinal product Monaflox, eye drops, should be discontinued.

Data on the efficacy and safety of moxifloxacin in the treatment of conjunctivitis in newborns are very limited. Therefore, its use in newborns is not recommended.

Monaflox should not be used for prophylactic purposes or for empirical treatment of gonococcal conjunctivitis, including neonatal gonococcal conjunctivitis in newborns, due to the presence of fluoroquinolone-resistant strains of Neisseria gonorrhoeae. Patients with ocular infections caused by Neisseria gonorrhoeae require appropriate systemic therapy.

The use of the drug is not recommended for the treatment of infections caused by Chlamydia trachomatis in patients under 2 years of age, as clinical studies have not been conducted in this population. Patients aged 2 years and older with ocular infections caused by Chlamydia trachomatis require appropriate systemic therapy.

Newborns with neonatal gonococcal conjunctivitis should be treated according to their clinical condition, i.e., systemic therapy should be administered in case of infection with Chlamydia trachomatis or Neisseria gonorrhoeae.

Patients should be advised not to wear contact lenses if they have symptoms of bacterial eye infection.

Use during pregnancy or breastfeeding.

Reproductive function

No studies on the effect of moxifloxacin on human reproductive function following topical administration have been conducted.

No adverse effects on the reproductive function of men or women have been reported during the use of the medicinal product Monaflox, eye drops.

Pregnancy

Since adequate and well-controlled studies on the effect of moxifloxacin in pregnant women have not been conducted, Monaflox should not be used during pregnancy except when the potential benefit outweighs the potential risk to the fetus.

Lactation period

It is not known whether moxifloxacin or its metabolites are excreted in human breast milk. Animal studies have shown low levels of moxifloxacin excretion after oral administration. Moxifloxacin should be used with caution in breastfeeding women.

Ability to affect reaction speed when driving or operating machinery.

As with the use of other eye drops, transient visual impairment or other visual disturbances may affect the ability to drive or operate machinery. If transient visual impairment occurs after administration of the medicinal product, the patient should wait until vision is fully restored before driving or operating machinery.

Method of Administration and Dosage

For ophthalmic use only. Not for injection. Subconjunctival injection or direct injection of the medicinal product Monafoks into the anterior chamber of the eye is prohibited.

Dosage

Use in adults, including elderly patients

The recommended dose is 1 drop of the medicinal product instilled into the affected eye(s) three times daily.

Improvement is usually observed within 5 days; however, treatment should be continued for an additional 2–3 days. If no improvement is observed within 5 days of initiating therapy, the accuracy of the diagnosis and (or) the appropriateness of the prescribed treatment should be re-evaluated. The duration of treatment depends on the severity of the disease, clinical course, and results of bacteriological examination.

Use in children

Dosage adjustment is not required.

Use in patients with hepatic or renal impairment

Dosage adjustment is not required.

Method of Administration

Instill into the eye.

To prevent contamination of the dropper tip and solution, care must be taken to ensure that the tip of the dispenser does not come into contact with the eyelids or adjacent areas.

To minimize systemic absorption of the drops through the nasal mucosa, especially in newborns and young children, it is recommended to press the lacrimal sac (nasolacrimal duct) with a finger for 2–3 minutes after instillation.

If more than one ophthalmic topical agent is being used, an interval of at least 5 minutes should be maintained between administrations. Ophthalmic ointments should be applied last.

Children

Do not use in children under 2 years of age.

In patients under 18 years of age, adverse reactions such as eye irritation and eye pain have been reported.

Overdose

There have been no reports of overdose with the medicinal product Monafoks. The limited capacity of the conjunctival sac practically excludes the possibility of overdose.

The amount of moxifloxacin in the bottle is too small to cause adverse effects following accidental ingestion.

Side effects

During clinical trials, the most commonly reported side effects were ocular pain and eye irritation, occurring in approximately 1–2% of patients.

The adverse reactions listed below are associated with the use of the medicinal product and are classified according to the frequency of their occurrence as follows: 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). Within each frequency group, adverse effects are listed in order of decreasing severity.

Blood and lymphatic system disorders

Uncommon: decreased hemoglobin levels.

Nervous system disorders

Common: taste disturbances.

Uncommon: headache, paraesthesia.

Eye disorders

Common: eye pain, eye irritation, dry eyes, eye pruritus, conjunctival hyperemia, eye hyperemia.

Uncommon: corneal epithelial damage, punctate keratitis, corneal pigmentation, conjunctival hyperemia, conjunctival haemorrhage, eyelid oedema, blepharitis, eyelid pain, conjunctivitis, eye oedema, eye discomfort, blurred vision, decreased visual acuity, eyelid disorders, eyelid erythema, increased eye sensitivity.

Rare: conjunctival oedema.

Respiratory, thoracic and mediastinal disorders

Uncommon: nasal discomfort, throat pain, foreign body sensation (in throat).

Gastrointestinal disorders

Uncommon: dysgeusia.

Rare: vomiting.

Hepatobiliary disorders

Uncommon: increased alanine aminotransferase (ALT) levels, gamma-glutamyl transferase.

The following adverse reactions have been observed during post-marketing studies of moxifloxacin. The frequency of these reactions is unknown (cannot be estimated from the available data).

Cardiac disorders:

Tachycardia.

Nervous system disorders:

Dizziness.

Eye disorders:

Endophthalmitis, ulcerative keratitis, corneal erosion, corneal abrasion, increased intraocular pressure, corneal opacity, corneal infiltrate, corneal deposits, allergic conjunctivitis, keratitis, corneal oedema, photophobia, corneal lesion, blepharitis, eyelid oedema, increased lacrimation, eye discharge, foreign body sensation.

Respiratory, thoracic and mediastinal disorders:

Dyspnoea.

Gastrointestinal disorders:

Nausea.

Skin and subcutaneous tissue disorders:

Erythema, skin rash, pruritus.

Immune system disorders:

Hypersensitivity reactions.

Pediatric studies

Results from clinical trials involving pediatric patients, including neonates, have shown that the type and severity of adverse effects are similar to those observed in adults.

Additional adverse reactions have been identified during post-marketing surveillance:

Skin and subcutaneous tissue disorders: urticaria.

With systemic administration of fluoroquinolones, tendon inflammation and tendon rupture may occur. Clinical studies and post-marketing experience with systemic quinolones indicate that the risk of such ruptures is increased in patients receiving corticosteroids, particularly elderly patients, and in those with high tendon stress, including the Achilles tendon (see section "Special precautions").

Serious, sometimes fatal, hypersensitivity reactions (anaphylactic) have been observed in patients receiving systemic quinolone therapy, occasionally after the first dose. Some of these reactions were accompanied by cardiovascular collapse, loss of consciousness, auditory symptoms, throat or facial oedema, dyspnoea, urticaria, and pruritus (see section "Special precautions").

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life: 3 years.

Shelf life after first opening of the container: 4 weeks.

Storage conditions: No special storage conditions required.

Packaging:

5 ml in a bottle with dropper and child-resistant cap; 1 bottle per cardboard box.

Prescription status:

Prescription only.

Manufacturer:

Manufacturer responsible for batch release:

Pharmasell International Betriebsgesellschaft mbH.

Manufacturer's address and place of business:

Ernst-Melchior-Gasse 20, 1020 Vienna, Austria.