Properties
What is it?
1. Product Name VIGAMOX 0.5% sterile ophthalmic solution 2. Qualitative and quantitative composition Active substance: 1 ml solution contains 5.45 mg moxifloxacin hydrochloride, equivalent to 5 mg moxifloxacin base. Excipients: For excipients, see section 6.1. 3. Dosage form Eye drops, solution VIGAMOX is a greenish-yellow solution. 4. Clinical features 4.1. Therapeutic indications VIGAMOX is indicated for the topical treatment of bacterial infections of the anterior segment of the eye caused by moxifloxacin-susceptible strains (see section 5.1). Official guidelines on the appropriate use of antibacterial agents should be taken into account. 4.2. Dosage and method of administration Dosage/frequency and duration of administration Use in adults and the elderly 1 drop should be instilled into the infected eye(s) 3 times a day. Treatment should be continued for the next 2-3 days. Method of administration For ophthalmic use. To avoid contamination of the dropper tip and the solution, care must be taken not to touch the dropper tip of the bottle to the eyelids, the eye area, or any other surface. To prevent absorption of the drops through the nasal mucosa, especially in newborns or young children, the lacrimal ducts should be closed with fingers for 2-3 minutes after instillation of the drops. Additional information on special populations Renal/hepatic impairment Oral pharmacokinetic parameters of moxifloxacin do not show significant differences in patients with mild to moderate hepatic and renal impairment. No studies have been conducted in patients with severe hepatic impairment. For topical use, no dose adjustment of VIGAMOX is required in patients with hepatic impairment due to low systemic exposure. Pharmacokinetic parameters of oral moxifloxacin do not differ significantly in patients with mild, moderate, and severe renal impairment. No dose adjustment of VIGAMOX is required in patients with renal impairment. Pediatric population No dose adjustment is required. (For detailed information, see section 4.4 - Special warnings and precautions for use) Geriatric population No differences in efficacy and safety are observed between the elderly and adults. 4.3. Contraindications VIGAMOX is contraindicated in individuals with hypersensitivity to moxifloxacin, other quinolones, or any of the ingredients of this product. 4.4. Special warnings and precautions for use For ophthalmic use only. This product must not be administered by injection. VIGAMOX is administered subconjunctivally or into the anterior chamber of the eye. Direct injection is not permitted. Serious and sometimes fatal hypersensitivity reactions have occurred in some patients receiving systemic quinolone therapy after the first dose. Sensitization (anaphylactic) reactions have been reported. In addition to other reactions, cardiovascular collapse, loss of consciousness, angioedema (including swelling of the larynx, pharynx, and face), airway obstruction, dyspnea, urticaria, and itching may occur. If an allergic reaction to VIGAMOX develops, discontinue use of the product. Emergency medical intervention may be necessary in case of serious acute hypersensitivity reactions to moxifloxacin or any other substance in the product. Oxygen administration and airway management should be provided according to clinical indications. Systemic medications, including moxifloxacin, especially in elderly patients and those concurrently treated with corticosteroids. Tendinitis and tendon rupture can occur with fluoroquinolone therapy, so treatment with VIGAMOX should be discontinued at the first sign of tendinitis. During fluoroquinolone therapy, including moxifloxacin, tendinitis and tendon rupture may occur, especially in patients concurrently taking corticosteroids and also in the elderly. Therefore, treatment with VIGAMOX should be discontinued at the first sign of tendon rupture. As with other antibacterial agents, prolonged use of moxifloxacin may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Information on the efficacy and safety of VIGAMOX in the treatment of neonatal conjunctivitis is limited. Therefore, the use of VIGAMOX is not recommended for the treatment of neonatal conjunctivitis. Due to the spread of fluoroquinolone-resistant Neisseria gonorrhoeae, VIGAMOX should not be used for the prophylaxis and empirical treatment of gonococcal conjunctivitis, including gonococcal ophthalmia neonatorum. VIGAMOX is not recommended for the treatment of Chlamydia trachomatis in patients younger than 2 years of age, as it has not been evaluated in this age group. In patients older than 2 years of age, appropriate systemic therapy should be used for eye infections caused by Chlamydia trachomatis. For newborns with ophthalmia neonatorum, appropriate treatment should be used, e.g., systemic therapy for Chlamydia trachomatis or Neisseria gonorrhoeae. Patients with signs and symptoms of bacterial conjunctivitis should not wear contact lenses. 4.5. Interactions with other medicinal products and other forms of interaction Although no drug interaction studies have been conducted with VIGAMOX, the topical ocular dose of moxifloxacin is very high. Systemic studies have been conducted at higher doses. Unlike some other fluoroquinolones, no clinically significant drug interactions have been reported between systemic moxifloxacin and itraconazole, theophylline, warfarin, digoxin, oral contraceptives, probenecid, ranitidine, or glibenclamide. If more than one topical ophthalmic product is used, the products should be administered at least 5 minutes apart. 4.6. Pregnancy and lactation General indications Pregnancy category: C. Women of reproductive potential/contraception Insufficient information is available. Pregnancy There are no adequate data on the use of VIGAMOX in pregnant women. Experimental studies in animals have shown reproductive toxicity after systemic administration (see 5.3). VIGAMOX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Lactation In animals, moxifloxacin is transferred into breast milk after oral administration. It is unknown whether moxifloxacin is excreted in human milk. Like other quinolones, moxifloxacin may damage articular cartilage in developing animals (see 5.3). Although minimal systemic exposure is expected after ocular administration in lactating mothers, VIGAMOX may be used during lactation only if the potential benefit justifies the potential risk. Reproductive toxicity/fertility Insufficient information is available. 4.7. Effects on ability to drive and use machines As with all other eye drops, temporary blurring of vision or other visual disturbances may affect the ability to drive or operate machinery. If blurring of vision occurs after instillation, the patient should refrain from driving or operating machinery until vision is restored. 4.8. Undesirable effects In clinical studies involving 2252 patients, 1900 of these patients received VIGAMOX three times daily and VIGAMOX eight times daily. The total safety population for this product consists of 1389 patients from the United States and Canada, 586 patients from Japan, and 277 patients from India. No serious ophthalmological or systemic adverse events were observed with VIGAMOX® in clinical studies. The most frequent adverse reactions observed with the use of this product were eye pain and eye irritation with an incidence of 1% to 2%. In 96% of patients who experienced these adverse effects, the severity of these adverse effects was mild, and treatment was discontinued in only 1 patient due to an adverse effect. Adverse effects identified are classified as follows: very common (≥1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to ≤1/100); rare (>1/10,000 to ≤1/1,000); very rare (≤1/10,000) or unknown frequency (frequency cannot be estimated from the available data). Blood and lymphatic system disorders Uncommon: decreased hemoglobin Immune system disorders Unknown: hypersensitivity Nervous system disorders Common: dysgeusia Uncommon: headache, paresthesia Unknown: somnolence Eye disorders Common: eye pain, eye irritation, dry eye, eye pruritus, conjunctival hyperemia, ocular hyperemia Uncommon: corneal epithelial defect, punctate keratitis, corneal staining, conjunctival hemorrhage, conjunctivitis, eye swelling, eye discomfort, blurred vision, decreased visual acuity, eyelid disorder, eyelid edema, eyelid erythema, abnormal eye swelling. Unknown: endophthalmitis, ulcerative keratitis, corneal erosion, corneal abrasion, increased intraocular pressure, corneal opacity, corneal infiltrates, corneal deposits, ocular allergy, keratitis, corneal edema, photophobia, corneal dissolution, blepharitis, eyelid foreign body extrusion. Sensation in eye. Cardiac disorders Unknown: palpitations Respiratory, thoracic and mediastinal disorders Uncommon: nasal discomfort, pharyngolaryngeal pain, foreign body sensation in throat Unknown: dyspnea Gastrointestinal disorders Uncommon: vomiting Unknown: nausea Hepatobiliary disorders Uncommon: increased alanine aminotransferase, increased gamma-glutamyltransferase Skin and subcutaneous tissue disorders Unknown: erythema, pruritus, rash, urticaria Additional information on special populations Pediatric population Based on clinical trial data (see section 5.1) involving pediatric patients, including neonates, the type and severity of adverse reactions in the pediatric population are the same as in adults. Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions. 4.9. Overdose and its treatment The conjunctival sac has a limited capacity for absorption of ophthalmic products, making overdose with VIGAMOX virtually impossible. The amount of moxifloxacin in this product is so low that accidental ingestion does not cause side effects. 5. Pharmacological properties 5.1. Pharmacodynamic properties Pharmacotherapeutic group: Ophthalmologicals, anti-infectives Moxifloxacin is a broad-spectrum, fourth-generation fluoroquinolone antibacterial agent, effective against Gram-positive and Gram-negative ocular pathogens, atypical microorganisms, and anaerobes. Mechanism of action Moxifloxacin is effective in vitro against a broad spectrum of Gram-positive and Gram-negative microorganisms. It exerts its effect by inhibiting topoisomerase II (DNA gyrase enzyme) and topoisomerase IV, which are essential for bacterial DNA replication, transcription, repair, and recombination. Resistance Resistance to fluoroquinolones, including moxifloxacin, is usually caused by chromosomal mutations encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, resistance to moxifloxacin may result from mutations in the MAR (multidrug resistance) and qnr (quinolone resistance) genes. Cross-resistance with beta-lactams, macrolides, and aminoglycosides is not expected due to differences in the mode of action. Breakpoints There are no official breakpoint values for susceptibility to moxifloxacin for topical ophthalmic use. Although breakpoints are used for systemic use, their validity for topical ophthalmic therapy is uncertain. The systemic breakpoint for moxifloxacin is ≤2 mg/L for susceptibility and >4 mg/L for resistance. Sensitization The rate of acquired resistance to moxifloxacin may vary geographically and over time for selected strains, and local information is very important, especially when treating serious infections. If necessary, there is at least local diffuse resistance. In cases where infection types are suspected, expert advice on the utility of the active substance is required. Generally susceptible species Aerobic Gram-positive microorganisms including Corynebacterium species Corynebacterium diphtheriae Staphylococcus aureus (methicillin-resistant) Streptococcus pneumoniae Streptococcus pyogenes Streptococcus viridans group Aerobic Gram-negative microorganisms Enterobacter cloacae Haemophilus influenzae Klebsiella oxytoca Moraxella catarrhalis Serratia marcescens Anaerobic microorganisms Proprionibacterium acnes Other microorganisms Chlamydia trachomatis Species where acquired resistance may be a problem Aerobic Gram-positive microorganisms Staphylococcus aureus (methicillin-resistant) Staphylococci, coagulase-negative strains (methicillin-resistant) Aerobic Gram-negative microorganisms Neisseria gonorrhoeae Other microorganisms Not specified. Organisms that are intrinsically resistant Aerobic Gram-negative microorganisms Pseudomonas aeruginosa Other microorganisms Not specified. The above information is based on microbiological screening studies conducted in various parts of Europe. Bacterial isolates from eye infections were obtained from Belgium, Czech Republic, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland, and England. VIGAMOX has been studied in a wide range of patients, from neonates to adults, including the elderly. 5.2. Pharmacokinetic properties Absorption and distribution Following topical ocular administration of VIGAMOX, moxifloxacin is absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were measured in 21 male and female subjects receiving VIGAMOX bilaterally in the eye 3 times daily for 4 days. The mean Cmax and AUC (EAA) at steady state were 2.7 ng/mL and 41.9 ng.hr/mL, respectively. These values are approximately 1600 and 1200 times lower than those of well-tolerated 400 mg oral therapeutic doses of moxifloxacin. Elimination The plasma half-life of moxifloxacin was 13 hours. 5.3. Preclinical safety data Effects on the hematopoietic system (slight decrease in red blood cell and platelet counts) were observed in rats and monkeys. Like other quinolones, hepatotoxicity (liver enzyme elevation and vacuolar degeneration) was observed in rats, monkeys, and dogs. CNS (central nervous system) toxicity (seizures) was observed in monkeys. These effects were observed only after high doses or prolonged treatment with moxifloxacin. Like other quinolones, moxifloxacin is genotoxic in bacteria and mammalian cells in vitro. If these effects are related to bacterial gyrase and interaction with topoisomerase II at even higher concentrations in mammalian cells, a threshold for genotoxicity can be assumed. In vivo tests did not show evidence of genotoxicity despite very high doses of moxifloxacin. Therefore, therapeutic doses for human use provide an adequate margin of safety. No evidence of carcinogenic effects was observed in rats. Most quinolones are photolabile and can cause phototoxic, photomutagenic, and photocarcinogenic effects. In contrast, in vitro and in vivo studies have shown that moxifloxacin does not have phototoxic and photogenotoxic properties. Similar effects have been observed with other quinolones under the same conditions. Reproductive toxicity Quinolones are known to damage cartilage in the large joints of developing animals. In puppies, moxifloxacin induced joint toxicity at oral doses of 30 mg/kg/day or higher. 6. Pharmaceutical properties 6.1. List of excipients Sodium chloride Boric acid Sodium hydroxide and/or hydrochloric acid (for pH adjustment) Purified water Does not contain preservatives. 6.2. Incompatibilities Unknown. 6.3. Shelf life 24 months. The product is sterile before opening. The product should be used within 28 days of opening; any unused product should be discarded. 6.4. Special storage conditions Store at a temperature not exceeding 25°C. To avoid contamination of the solution, do not touch the dropper tip to any surface.
