Cytomoxan®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CYTOMOXAN® (CYTOMOXAN)

Composition:

Active substance: moxifloxacin;

1 ml of eye drops contains 5.45 mg moxifloxacin hydrochloride (calculated as 100% anhydrous substance), equivalent to 5 mg moxifloxacin;

Excipients: sodium chloride, boric acid, 1 M hydrochloric acid solution, sodium hydroxide, water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear yellow to yellow-green liquid.

Pharmacotherapeutic group. Ophthalmological agents. Antibacterials. Fluoroquinolones. Moxifloxacin. 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 mar (multiple antibiotic 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):

The in vitro breakpoints are used to predict the clinical efficacy of moxifloxacin when administered systemically. These breakpoints may not be appropriate for topical ocular use of the drug, as higher concentrations are used with topical administration and local physical/chemical conditions at the site of application may influence the drug's activity.

Susceptibility

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

If necessary, advice from a specialist should be sought when local resistance prevalence renders the activity of moxifloxacin at least questionable against certain types of infections.

Preclinical safety data

During preclinical studies, effects following topical ocular administration were observed only when doses greatly exceeding the maximum human dose were used, indicating minimal relevance to clinical use.

Like other quinolones, moxifloxacin was found to be genotoxic in vitro in bacterial and mammalian cells. A threshold level for genotoxicity can be assumed, as these effects may occur at significantly higher concentrations due to interactions with bacterial gyrase and mammalian topoisomerase II. However, in in vivo studies, despite high doses of moxifloxacin, no evidence of genotoxicity was found. Thus, therapeutic doses in humans provide an adequate safety margin. No signs of carcinogenic potential were observed in preclinical studies in rats.

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

Pharmacokinetics.

After topical administration of moxifloxacin as eye drops, the drug was absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were measured in 21 subjects—both men and women—who received the medication topically in both eyes three times daily for 4 days. The mean peak plasma concentration (C_max) and the area under the concentration-time curve (AUC) were 2.7 ng/mL and 41.9 ng·h/mL, respectively. These values are approximately 1600 and 1200 times lower, respectively, than the mean C_max and AUC values reported after oral administration of the therapeutic dose of 400 mg of moxifloxacin. The elimination half-life of moxifloxacin in plasma is 13 hours.

Clinical characteristics.

Indications.

Local treatment of bacterial conjunctivitis caused by bacterial strains sensitive to moxifloxacin.

For information on the appropriate use of antibacterial agents, refer to official guidelines.

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 interaction studies with other medicinal products have been conducted. Interaction with other medicinal products is unlikely due to low systemic concentrations of moxifloxacin following topical ophthalmic administration. If multiple topical ophthalmic medicinal products are prescribed simultaneously, the interval between their administration should be at least 5 minutes. Ophthalmic ointments should be administered last.

Special precautions for use.

• For ophthalmic use only. Not for injection. Subconjunctival injection or direct injection of Citomoxan® eye drops into the anterior chamber of the eye is contraindicated.
• In patients receiving systemic quinolone therapy, severe, sometimes fatal, hypersensitivity reactions (anaphylactic reactions) have been reported, occasionally after the first dose. Some of these reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including swelling of the larynx, pharynx, and face), airway obstruction, dyspnea, urticaria, and pruritus.
• If an allergic reaction to Citomoxan® eye drops occurs, the drug should be discontinued immediately. Severe acute hypersensitivity reactions to moxifloxacin or any component of this medicinal product may require emergency treatment. If clinically indicated, airway patency should be restored and oxygen therapy initiated.
• As with other antibiotics, prolonged use of Citomoxan® eye drops may result in overgrowth of non-susceptible microorganisms, including fungi. If superinfection occurs, treatment should be discontinued and appropriate therapy initiated.
• With systemic therapy with fluoroquinolones, including moxifloxacin, tendon inflammation and tendon rupture may occur, particularly in elderly patients and in those receiving concomitant corticosteroid therapy. At the first sign of tendon inflammation, treatment with Citomoxan® eye drops should be discontinued.
• Wearing of contact lenses is not recommended during treatment of ocular inflammation/infection.
• The drug is not indicated for children under 2 years of age for the treatment of eye diseases caused by Chlamydia trachomatis, as its efficacy has not been studied in this patient population. Children aged 2 years and older with eye diseases caused by Chlamydia trachomatis should receive appropriate systemic therapy. Newborns should receive appropriate systemic therapy in case of eye infection caused by Chlamydia trachomatis or Neisseria gonorrhoeae.

Use during pregnancy or breastfeeding.

Reproductive function

No studies on the effect of Citomoxan® eye drops on human reproductive function following topical administration have been conducted.

There have been no reports of adverse effects on reproductive function in men or women during treatment with moxifloxacin hydrochloride eye drops.

Pregnancy

Since adequate and well-controlled studies of the use of the drug in pregnant women have not been conducted, Citomoxan® should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding 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. Citomoxan® should be used with caution in breastfeeding women.

Ability to affect reaction speed when driving or operating machinery.

Citomoxan® eye drops have no effect or have a negligible effect on the ability to drive or operate machinery. Transient blurred vision or other visual disturbances may affect the ability to drive or operate machinery. If blurred vision occurs after instillation, patients should wait until vision clears before driving or operating machinery.

Method of administration and dosage.

For ophthalmic use.

Adults, including elderly patients

Instill 1 drop into the affected eye(s) 3 times daily.

The condition usually improves within 5 days; treatment should then be continued for an additional 2–3 days. If no improvement is observed within 5 days of treatment, consult a physician for reassessment of diagnosis and/or therapy. The duration of treatment depends on the severity of the disease and the clinical and bacteriological response.

Children

No dose adjustment is required in this patient population.

Patients with hepatic or renal impairment

No dose adjustment is required in this patient population.

To prevent contamination of the dropper tip and the contents of the bottle, care must be taken not to touch the eyelids, adjacent areas, or other surfaces with the tip of the dropper bottle.

To minimize systemic absorption through the nasal mucosa, especially in newborns and children, occlusion of the nasolacrimal duct for 2–3 minutes after instillation is recommended.

Not for injection. Subconjunctival injection or direct injection into the anterior chamber of the eye with Cytomoxan® is contraindicated.

Children.

In clinical trials, ophthalmic drops containing moxifloxacin hydrochloride were found to be safe when used in children, including newborns. In patients under 18 years of age, two adverse reactions were reported: eye irritation and eye pain (incidence – 0.9%). See also section "Special precautions for use".

Overdose.

Due to the characteristics of the drug, no toxic effects are expected in case of overdose when the drug is administered into the eye or following accidental ingestion of the contents of one bottle.

Adverse reactions.

During clinical studies, the most commonly reported adverse reactions were eye pain and eye irritation, occurring in approximately 1 – 2% of patients.

The adverse reactions listed below were observed during clinical trials of moxifloxacin hydrochloride ophthalmic solutions and are classified as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), and very rare (< 1/10000). Within each frequency category, adverse reactions are listed in order of decreasing severity.

Additional adverse reactions have been identified during the post-marketing surveillance period. The frequency of their occurrence cannot be estimated. Within each organ system, adverse reactions are listed in order of decreasing severity.

In patients who have received systemic therapy with quinolones, serious, sometimes fatal, hypersensitivity reactions (anaphylactic) have been observed, occasionally after the first dose. Some of these reactions were accompanied by cardiovascular collapse, loss of consciousness, tinnitus, swelling of the throat or face, dyspnea, urticaria, and pruritus (see section "Special precautions for use").

Tendon inflammation and tendon ruptures may occur with systemic administration of fluoroquinolones. Studies and post-marketing experience with systemic quinolones indicate that the risk of such ruptures may be increased in patients receiving corticosteroids, particularly in elderly patients, and with high stress on tendons, including the Achilles tendon (see section "Special precautions for use").

Reporting of suspected adverse reactions

Reporting of adverse reactions after drug registration is important. It allows ongoing 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 via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years. Shelf life after opening the vial is 28 days.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging. 5 ml in a vial. 1 vial in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and location of its business activities.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.