Moxacin

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

Composition:

Active substance: moxifloxacin;

1 ml of solution contains moxifloxacin hydrochloride 5.45 mg, equivalent to 5 mg of moxifloxacin;

Excipients: sodium chloride, boric acid, sodium hydroxide (for pH adjustment), purified water.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: green-yellow clear solution, practically free from particles.

Pharmacotherapeutic group. Agents used in ophthalmology. Antibacterial agents. 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 through 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 (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 when the drug is applied topically to the eye, as higher concentrations are used with topical administration and local physical/chemical conditions may influence the activity of the drug at the site of application.

Susceptibility

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

If necessary, expert advice should be sought when local resistance prevalence is such that the activity of moxifloxacin, at least against certain types of infections, is questionable.

Preclinical safety data

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

As with other quinolones, moxifloxacin was found to be genotoxic in vitro in bacterial and mammalian cells. A threshold level for genotoxicity can be assumed, since at substantially higher concentrations these effects may result from interactions with bacterial gyrase and topoisomerase II in mammalian cells. However, in in vivo studies, no evidence of genotoxicity was observed despite high doses of moxifloxacin. Therefore, 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.

Following topical ocular administration of Moxacin eye drops, moxifloxacin was absorbed into the systemic circulation. Moxifloxacin plasma concentrations were measured in 21 subjects—both male and female—who received the medicinal product administered topically to both eyes three times daily for 4 days. The mean peak plasma concentration (Cmax) and the area under the concentration-time curve (AUC) in plasma were 2.7 ng/mL and 41.9 ng·h/mL, respectively. These values are approximately 1600 and 1200 times lower than the mean Cmax and AUC values reported after oral administration of therapeutic doses of moxifloxacin (400 mg). The elimination half-life of moxifloxacin in plasma is 13 hours.

Clinical characteristics.

Indications.

Local treatment of bacterial conjunctivitis caused by moxifloxacin-susceptible bacterial strains. For information on appropriate use of antibacterial agents, refer to official guidelines.

Contraindications.

Hypersensitivity to the active substance, to other quinolones, or to any of the components 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 several 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 into the anterior chamber of the eye with Moxacin is prohibited.
• In patients receiving systemic therapy with quinolones, serious, sometimes fatal, hypersensitivity reactions (anaphylactic reactions) have been observed, occasionally after administration of the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal, and facial swelling), airway obstruction, dyspnea, urticaria, and pruritus.
• If an allergic reaction to Moxacin eye drops occurs, the drug should be discontinued. 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 Moxacin 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 using fluoroquinolones, including moxifloxacin, tendon inflammation and tendon rupture may occur, particularly in elderly patients and with concomitant corticosteroid use. The plasma concentration of moxifloxacin after ophthalmic administration of Moxacin is considerably lower than after therapeutic oral administration of moxifloxacin; however, caution is advised, and treatment with Moxacin should be discontinued at the first signs of tendon inflammation.
• It is not recommended to wear contact lenses during treatment of eye inflammation/infection.
• The drug should not be administered to children under 2 years of age for 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 involvement caused by Chlamydia trachomatis or Neisseria gonorrhoeae.

Use during pregnancy or breastfeeding.

Reproductive function

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

No adverse effects on reproductive function in men or women have been reported during use of Moxacin eye drops.

Pregnancy

There are insufficient data on the use of this medicinal product in pregnant women. However, systemic exposure to moxifloxacin is negligible, and therefore, no adverse effects on the organism during pregnancy are expected. The medicinal product may be used during pregnancy.

Breastfeeding period

It is not known whether moxifloxacin/metabolites are excreted in human breast milk. Animal studies have shown low levels of moxifloxacin excretion after oral administration. However, no effects of the drug on breastfed infants are expected when therapeutic doses are used. The medicinal product may be used during breastfeeding.

Effects on ability to drive and use machines.

Moxacin eye drops have no or negligible influence 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.

Dosage and Administration

For ophthalmic use only.

Adults, including elderly patients

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

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

Children

No dose adjustment is necessary for this patient group.

Patients with hepatic or renal impairment

No dose adjustment is necessary for this patient group.

To prevent contamination of the dropper tip and the contents of the bottle, care should be taken not to touch the eyelids, surrounding areas, or other surfaces with the tip of the dropper bottle. To minimize systemic absorption via the nasolacrimal duct, especially in newborns and children, nasolacrimal occlusion is recommended for 2–3 minutes after instillation of the drops.

Not for injection. Intravenous or intraocular injection of Moxacin is strictly contraindicated. Subconjunctival injection or direct injection into the anterior chamber of the eye must be avoided.

Children

In clinical studies, moxifloxacin ophthalmic solution was found to be safe in children, including newborns. In patients under 18 years of age, two adverse reactions were reported: eye irritation and eye pain (incidence rate of 0.9%). See also section "Special precautions".

Overdose

Due to the characteristics of the drug, toxic effects are not expected in case of overdose when administered topically to the eye or following accidental ingestion of the contents of one bottle.

Adverse Reactions

Clinical studies have not revealed any serious ophthalmological or systemic adverse reactions associated with the use of the medicinal product. The most commonly reported adverse events related to the use of the drug were eye irritation and eye pain, observed in 1-2% of cases. These reactions were mild in 96% of patients in whom they occurred, and treatment was discontinued in only one patient.

The adverse reactions listed below are classified by frequency as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), and very rare (<1/10,000); frequency not known – cannot be estimated from available data. Within each category, adverse effects are listed in decreasing order of severity.

Blood and lymphatic system disorders

Rare: Decreased hemoglobin levels.

Nervous system disorders

Uncommon: Headache; rare: Paraesthesia.

Frequency not known: Dizziness.

Eye disorders

Common: Eye pain, eye irritation.

Uncommon: Punctate keratitis, dry eye syndrome, conjunctival haemorrhage, conjunctival hyperaemia, eye hyperaemia, eye pruritus, abnormal eye sensation, eyelid oedema, ocular discomfort.

Rare: Corneal epithelial defect, corneal disorder, corneal pigmentation, conjunctivitis, blepharitis, eye swelling, eyelid pain, conjunctival oedema, blurred vision, reduced visual acuity, asthenopia, eyelid disorder, eyelid erythema.

Frequency not known: Ulcerative keratitis, keratitis, increased lacrimation, photophobia, eye discharge, foreign body sensation in the eye.

Respiratory, thoracic and mediastinal disorders

Rare: Nasal discomfort, pharyngolaryngeal pain, foreign body sensation (in throat).

Frequency not known: Dyspnoea.

Gastrointestinal disorders

Uncommon: Dysgeusia; rare: Vomiting.

Frequency not known: Nausea.

Hepatobiliary disorders

Rare: Increased alanine aminotransferase levels, increased gamma-glutamyl transferase levels.

Immune system disorders

Frequency not known: Hypersensitivity.

Cardiac disorders

Frequency not known: Tachycardia.

Skin and subcutaneous tissue disorders

Frequency not known: Erythema, pruritus, rash, urticaria.

In patients receiving systemic quinolone therapy, serious and sometimes fatal hypersensitivity reactions (anaphylactic) have been observed, occasionally after administration of the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tinnitus, swelling of the throat or face, dyspnoea, urticaria, and pruritus (see section "Special precautions").

Tendon inflammation and rupture may occur with systemic use of fluoroquinolones. Clinical 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 tendon stress, including the Achilles tendon (see section "Special precautions").

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 via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

The shelf life after first opening of the dropper bottle is no more than 28 days.

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 dropper bottle; 1 dropper bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Jadran-Galenski Laboratorij d.d. / Jadran-Galenski Laboratorij d.d.

Manufacturer's address and place of business.

Svilno 20, 51000 Rijeka, Croatia / Svilno 20, 51000 Rijeka, Croatia.