Vigamox

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

Composition:

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

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

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear, greenish-yellow solution.

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 from chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, resistance to moxifloxacin may also arise 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 relevant microorganisms; therefore, local information on microbial resistance patterns should be sought, especially when treating severe infections.

If necessary, expert advice should be consulted 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 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 considerably higher concentrations these effects may lead to interaction with bacterial gyrase and topoisomerase II in mammalian cells. However, in in vivo studies, no evidence of genotoxicity was found despite high doses of moxifloxacin. 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

Following topical ocular administration of VIGAMOX® eye drops, moxifloxacin was absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were measured in 21 subjects—both male and female—who received the medication topically in both eyes three times daily for four 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 the therapeutic dose of 400 mg of 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. 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 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 Vigamox® is contraindicated.
• Serious, sometimes fatal, hypersensitivity reactions (anaphylactic reactions) have been reported in patients receiving systemic quinolone therapy, 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 Vigamox®, 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 Vigamox® eye drops may result in overgrowth of non-susceptible microorganisms, including fungi. If superinfection occurs, treatment should be discontinued and appropriate therapy initiated.
• Tendon inflammation and tendon rupture may occur during systemic therapy with fluoroquinolones, including moxifloxacin, particularly in elderly patients and those receiving concomitant corticosteroid therapy. Treatment with Vigamox® eye drops should be discontinued at the first sign of tendon inflammation.
• Wearing of contact lenses is not recommended during treatment of eye infections/inflammations.
• 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 with eye infections caused by Chlamydia trachomatis or Neisseria gonorrhoeae should receive appropriate systemic therapy.

Use during pregnancy or breastfeeding.

Reproductive function

No studies on the effect of Vigamox® 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 Vigamox® eye drops.

Pregnancy

Since adequate and well-controlled studies of the use of the drug in pregnant women have not been conducted, Vigamox® should not be used during pregnancy unless the potential benefit justifies 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. Vigamox® should be used with caution in nursing women.

Ability to influence reaction rate while driving or operating machinery.

Vigamox® eye drops have no or 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, the patient 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) 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, 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 for this patient group.

Patients with hepatic or renal impairment

No dose adjustment is required for 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 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.

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

Children.

In clinical studies, VIGAMOX® 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 – 0.9%). See also section "Special Warnings and Precautions for Use".

Overdose.

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

Adverse reactions

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

The adverse reactions observed during clinical studies with VIGAMOX® are listed below and 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 frequency category, 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, serious, 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, dyspnea, urticaria, and pruritus (see section "Special precautions for use").

Tendon inflammation and tendon ruptures 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 elderly patients, and with high tendon stress, including the Achilles tendon (see section "Special precautions for use").

Shelf life. 3 years.

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

Storage conditions.

No special storage conditions are required. Store in a place inaccessible to children.

Packaging.

5 ml in a dropper bottle; 1 dropper bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Alcon Couvreur.

Alcon Couvreur.

Manufacturer's address and location of operations.

Rijksweg 14, Puurs-Sint-Amands, 2870, Belgium
Rijksweg 14, Puurs-Sint-Amands, 2870, Belgium.