Moxifloxacin-pharmex

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MOKSIFLOXACIN-PHARMEX (MOXIFLOXACIN-PHARMEX)

Composition:

Active substance: moxifloxacin;

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

Excipients: sodium chloride, boric acid, sodium hydroxide and/or hydrochloric acid diluted (for pH adjustment), water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear greenish-yellow solution.

Pharmacotherapeutic group.
Ophthalmological agents. Antibacterials. 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 (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 drug's activity 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, 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 at doses significantly exceeding the maximum human dose, suggesting minimal relevance to clinical use.

As with other quinolones, moxifloxacin was found to be genotoxic in vitro in bacterial and mammalian cells. A threshold for genotoxicity may be assumed, as these effects occur at much higher concentrations that may lead to interaction with bacterial gyrase and topoisomerase II in mammalian cells. However, in in vivo studies, despite high doses of moxifloxacin, no evidence of genotoxicity was observed. 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 did not show any phototoxic or photogenotoxic properties in extensive in vitro and in vivo studies.

Pharmacokinetics

Following topical administration of moxifloxacin eye drops, the drug was absorbed into the systemic circulation. Moxifloxacin plasma concentrations were measured in 21 subjects—both male and female—who received the medication topically in both eyes three times daily for 4 days. The mean peak plasma concentration (Cmax) and 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 Cmax and AUC values reported after oral administration of therapeutic doses of 400 mg moxifloxacin. The plasma half-life of moxifloxacin is 13 hours.

Clinical characteristics.

Indications.

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

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.

Studies on interaction with other medicinal products have not 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 applied 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 moxifloxacin is contraindicated.

In patients receiving systemic therapy with quinolones, severe, and sometimes fatal, hypersensitivity reactions (anaphylactic reactions) have been reported, occasionally after the first dose. Some of these reactions have been 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 moxifloxacin ophthalmic solution 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 maintained and oxygen therapy administered.

As with the use of other antibiotics, prolonged use of moxifloxacin ophthalmic solution may result in overgrowth of non-susceptible microorganisms, including fungi. If superinfection occurs, discontinue treatment and institute appropriate therapy.

With systemic therapy using fluoroquinolones, including moxifloxacin, tendon inflammation and tendon rupture may occur, particularly in elderly patients and those receiving concomitant corticosteroid therapy. At the first sign of tendinitis, treatment with moxifloxacin ophthalmic solution should be discontinued.

It is not recommended to wear contact lenses during treatment of eye inflammation/infection.

The drug is not indicated for use in 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 for eye infections caused by Chlamydia trachomatis or Neisseria gonorrhoeae.

Use during pregnancy or breastfeeding

Reproductive function

Studies on the effect of moxifloxacin on human reproductive function following topical administration have not been conducted.

There have been no reports of adverse effects on the reproductive function of men or women during use of moxifloxacin ophthalmic solution.

Pregnancy

Since adequate and well-controlled studies of the use of this drug in pregnant women have not been conducted, moxifloxacin should not be used during pregnancy unless the potential benefit justifies 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. Moxifloxacin should be used with caution in women who are breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Moxifloxacin ophthalmic solution has 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.

Method of Administration and Dosage

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 observed 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 required in this patient group.

Patients with hepatic or renal impairment

No dose adjustment is required in this patient group.

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

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

Do not use for injections. Subconjunctival injection or direct injection into the anterior chamber of the eye is contraindicated.

Children.

Clinical studies have shown that moxifloxacin ophthalmic solution is safe for use in children, including newborns. In patients under 18 years of age, two adverse reactions have been 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 the drug is administered into the eye or if the contents of one bottle are accidentally swallowed.

Adverse reactions

According to clinical trial data, the most commonly reported adverse reactions were ocular pain and eye irritation, occurring in approximately 1–2% of patients.

The adverse reactions listed below, observed during moxifloxacin studies, 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). Within each group, adverse effects 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 receiving systemic therapy with quinolones, severe, sometimes fatal hypersensitivity reactions (anaphylactic) have been observed, occasionally after administration of the first dose. Some reactions were accompanied by cardiovascular insufficiency, loss of consciousness, tinnitus, swelling of the throat or face, dyspnea, urticaria, and pruritus (see section "Special precautions").

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

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare 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/.

All cases of adverse reactions must be reported to the manufacturer:

PHARMEKS GROUP LLC, Ukraine, 08301, Kyiv region, Boryspil, Shevchenka St., 100, tel.: +38(044)391-19-19, fax: +38(044)391-19-18, or via the form on the website: http://www.pharmex.com.ua/farmakonadzor.

Shelf life. 3 years.

Storage period after first opening of the vial – 4 weeks.

Storage conditions.

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

Keep out of reach of children.

Packaging.

5 ml in a vial, 1 vial with a dropper cap in a cardboard pack.

Prescription status.

By prescription only.

Manufacturer.

PHARMEKS GROUP LLC.

Manufacturer's address and location of business activity.

Ukraine, 08301, Kyiv region, Boryspil, Shevchenka St., 100.