Vigamox

Vigamox

moxifloxacin

Manufacturer:

Novartis Healthcare

Distributor:

Mundipharma
Full Prescribing Info
Contents
Moxifloxacin hydrochloride.
Description
1 mL of solution contains 5.45 mg moxifloxacin hydrochloride equivalent to 5 mg moxifloxacin base. Each eye drop contains 190 micrograms of moxifloxacin.
Contains: Active: Moxifloxacin 0.5% (5 mg/mL); Preservative: None. Product is self preserved. Inactives: sodium chloride, boric acid and purified water. May also contain hydrochloric acid/sodium hydroxide to adjust pH. MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution is isotonic and formulated at pH 6.8 with an osmolality of approximately 290 mOsm/kg.
MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution 0.5% is a sterile topical ophthalmic solution. Moxifloxacin is a fourth-generation fluoroquinolone antibacterial agent active against a broad spectrum of Gram-positive and Gram-negative ocular pathogens, atypical microorganisms and anaerobes.
C21H24FN3O4•HCl. Mol Wt: 437.9.
Chemical Name: 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7[(4aS,7aS)-octahydro-6H-pyrrolol[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid, monohydrochloride. Moxifloxacin differs from other quinolones in that it has a methoxy function at the 8 position, and an S,S-configured diazabicyclononyl ring moiety at the 7-position.
Moxifloxacin hydrochloride is slightly yellow to yellow crystalline powder.
Action
Pharmacology: Pharmacokinetics/Pharmacodynamics: Following topical ocular administration of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution, moxifloxacin was absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were measured in 21 male and female subjects who received bilateral topical ocular of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution 3 times a day for 4 days. The mean steady-state Cmax and AUC were 2.7 ng/mL and 41.9 ng hr/mL respectively. These exposure values are approximately 1,600 and 1,200 times lower than the mean Cmax and AUC reported after well tolerated therapeutic 400 mg oral doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.
Clinical Studies: MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution has been studied in patients from newborns to adults, including geriatric patients.
In three randomized, double-masked, multicenter, controlled clinical trials in which patients were dosed 3 times a day for 4 days. MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution produced clinical cures in 80% to 94% of patients treated for bacterial conjunctivitis. Microbiological success rates for the eradications of the baseline pathogens ranged from 85% to 97%. In one of these trials in pediatric patients from birth to one month of age, MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution produced clinical cure in 80% of patients with bacterial conjunctivitis. The microbiological success rate for the eradication of the baseline pathogens was 92%.
In the randomized, double-masked, multicenter, controlled clinical trial in which patients were dosed 2 times a day for 3 days, MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution produced clinical cure in 74% of patients treated for bacterial conjunctivitis. Microbiological success rate for the eradication of the baseline pathogens was 81%.
Special Population: The pharmacokinetic parameters of oral moxifloxacin are not significantly altered by mild, moderate or severe renal impairment. No dosage adjustment of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution is necessary in patients with renal impairment. Pharmacokinetic parameters of oral moxifloxacin were not significantly altered in patients with mild to moderate hepatic insufficiency (Child Pugh Classes A and B). Studies were not performed in patients with severe hepatic impairment (Child Pugh Class C). Because of the low systemic exposure by the topical route of administration, no dosage adjustment of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution is needed in patients with hepatic impairment.
Microbiology: Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative microorganisms. Moxifloxacin inhibits the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair and recombination. The C8-methoxy moiety of moxifloxacin also lessens the selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety found in older fluoroquinolones. Moxifloxacin's bulky C-7 substituent group interferes with the quinolone efflux pump mechanism of bacteria.
Moxifloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations. Fluoroquinolones, including moxifloxacin, differ in chemical structure and mode of action from B-lactam antibiotics, macrolides and aminoglycosides, and therefore may be active against bacteria resistant B-lactam antibiotics, macrolides and aminoglycosides. Therefore, organisms resistant to these drugs may be susceptible to moxifloxacin. In vitro resistance to moxifloxacin develops slowly via multiple-step mutations and occurs at a general frequency between 10-9 to 10-11 for Gram-positive bacteria.
Moxifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the Indications: Gram-positive bacteria: Corynebacterium species, Microbacterium species, Micrococcus luteus [including erythromycin, gentamicin, tetracycline, and/or trimethoprim resistant strains], Staphylococcus aureus [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus epidermidis [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus haemolyticus [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus hominis [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus warneri [including erythromycin resistant strains], Streptococcus mitis [including penicillin, erythromycin, tetracycline and/or trimethoprim resistant strains], Streptococcus pneumoniae [including penicillin, erythromycin, gentamicin, tetracycline and/or trimethoprim resistant strains], Streptococcus viridans [including penicillin, erythromycin, tetracycline and/or trimethoprim resistant strains].
Gram-negative bacteria: Acinetobacter species, Haemophilus "alconae" [including ampicillin resistant strains], Haemophilus influenzae [including ampicillin resistant strains], Klebsiella pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa.
Other microorganisms: Chlamydia trachomatis.
Moxifloxacin has been shown to be active in vitro against most strains of the following organisms; however, the clinical significance of these data is unknown.
Gram-Positive Bacteria: Arthrobacter species, Bacillus cereus, Bacillus thuringensis, Corynebacterium accolens, Corynebacterium amycolatum, Corynebacterium bovis, Corynebacterium macginleyi, Corynebacterium propinquum, Corynebacterium pseudodiptheriticum, Enterococcus faecalis, Exiguobacterium species, Kocuria kristinae, Kocuria "lindaea", Kocuria rhizophila, Microbacterium "harmaniae", Microbacterium "otitidis", Rothia mucilaginosus, Staphylococcus arlettae, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus cohnii, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus saprophyticus, Staphylococcus sciuri, Streptococcus "conjunctivae", Streptococcus cristatus, Streptococcus dysgalactiae, Streptococcus "ocularis", Streptococcus oralis, Streptococcus parasanguinis, Streptococcus pyogenes, Streptococcus salivarius, Streptococcus sanguis, Streptococcus "schlechii".
Gram-Negative Bacteria: Achromobacter xylosoxidans, Acinetobacter baumani, Acinetobacter johnsonii, Acinetobacter junii, Acinetobacter lwoffi, Acinetobacter "mumbaiae", Acinetobacter schindleri, Acinetobacter ursingii, Aeromonas caviae, Chryseobacterium indologenes, Chryseobacterium species, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter hormaechei, Escherichia coli, Klebsiella oxytoca, Moraxella osloensis, Morganella morganii, Pantoea agglomerans, Proteus mirabilis, Pseudomonas orzyihabitans, Pseudomonas stutzeri, Serratia liquefaciens, Serratia marcescens, Stenotrophomonas maltophilia.
Anaerobic Microorganisms: Fusobacterium species, Porphyromonas species, Prevotella species, Propionibacterium acnes.
Other organisms: Atypical Mycobacterium, Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.
Indications/Uses
MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution is indicated for: The treatment of corneal epithelial inflammation or corneal ulcer; Pre-operative and post-operative sterilization; The treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Gram-positive bacteria: Corynebacterium species*, Microbacterium species, Micrococcus luteus* [including erythromycin, gentamicin, tetracycline, and/or trimethoprim resistant strains], Staphylococcus aureus [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus epidermidis [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus haemolyticus [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus hominis* [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus warneri* [including erythromycin resistant strains], Streptococcus mitis* [including penicillin, erythromycin, tetracycline and/or trimethoprim resistant strains], Streptococcus pneumoniae [including penicillin, erythromycin, gentamicin, tetracycline and/or trimethoprim resistant strains], Streptococcus viridians [including penicillin, erythromycin, tetracycline and/or trimethoprim resistant strains].
Gram-negative bacteria: Acinetobacter species, Haemophilus "alconae" [including ampicillin resistant strains], Haemophilus influenzae [including ampicillin resistant strains], Klebsiella pneumonia*, Moraxella catarrhalis*, Pseudomonas aeruginosa*.
Other microorganisms: Chlamydia trachomatis.
*Efficacy for this organism was studied in fewer than 10 infections.
Dosage/Direction for Use
Corneal epithelial inflammation/corneal ulcer: Administer one drop in the affected eye three time (3x) per day for 7-14 days. The dose may be increased up to eight times (8x) per day depending on clinical symptoms.
For pre-operative and post-operative sterilization: Instill one drop in the affected eye five times (5x) per day 2 days before the operation and three times (3x) per day from the day of surgery (Day 1) to after 14 days (Day 14).
For bacterial conjunctivitis: Instill one drop in the affected eye three times (3x) a day for 4 days.
Overdosage
Due to the characteristics of this preparation no toxic effects are to be expected with an ocular overdose of the product, or in the event of accidental ingestion of the contents of one bottle.
Contraindications
MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution is contraindicated in patients with a history of hypersensitivity to the active substance, to other quinolones or to any of the excipients.
Warnings
For ocular use only. Not for injection. MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution should not be injected subconjunctivally or introduced directly into the anterior chamber of the eye.
In patients receiving systemically administered quinolones, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial oedema), airway obstruction, dyspnoea, urticaria, and itching. If an allergic reaction to MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution occurs, discontinue use of the product. Serious acute hypersensitivity reactions to moxifloxacin may require immediate emergency treatment. Oxygen and airway management should be administered where clinically indicated.
Special Precautions
General: As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy, and, where appropriate, fluorescein staining.
Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.
Tendon inflammation and rupture may occur with systemic fluoroquinolone therapy including moxifloxacin, particularly in elderly patients and in those treated concurrently with corticosteroids. Therefore, treatment with MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution should be discontinued at the first sign of tendon inflammation.
Information for Patients: Avoid contaminating the applicator tip with material from the eye, fingers or other source. Systemically administered quinolones have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact the physician at the first sign of rash or allergic reaction.
Effects on ability to drive and use machine: Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at application, the patient must wait until the vision clears before driving or using machinery.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Given the low systemic concentration of moxifloxacin following topical ocular administration of the medicinal product, drug interactions are unlikely to occur. Moxifloxacin was not mutagenic in four bacterial strains used in the Ames Salmonella reversion assay. As with other quinolones, the positive response observed with moxifloxacin in strain TA 102 using the same assay may be due to the inhibition of DNA gyrase. Moxifloxacin was not mutagenic in the CHO/HGPRT mammalian cell gene mutation assay. An equivocal result was obtained in the same assay when v79 cells were used. Moxifloxacin was clastogenic in the v79 chromosome aberration assay, but it did not induce unscheduled DNA synthesis in cultured rat hepatocytes. There was no evidence of genotoxicity in vivo in a micronucleus test or a dominant lethal test in mice.
Moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 21,700 times the highest recommended total daily human ophthalmic dose.
Long term studies in animals to determine the carcinogenic potential of moxifloxacin have not been performed. However, in an accelerated study with inhibitors and promoters, moxifloxacin was not carcinogenic following up to 38 weeks of oral dosing at 500 mg/kg/day.
Use in Children: MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution has shown to be safe and effective in pediatric patients including neonates. There is no evidence that the ophthalmic administration of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution has any effect on weight bearing joints, even though oral administration of some quinolones has been shown to cause arthropathy in immature animals.
Use in Elderly: No overall differences in safety and effectiveness have been observed between elderly and other adult patients.
Use In Pregnancy & Lactation
Fertility: Fertility Studies have not been performed to evaluate the effect of ocular administration of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution on fertility.
Use in Pregnancy: Teratogenic Effects: Pregnancy Category C: Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis at oral doses as high as 500 mg/kg/day (approximately 21,700 times the highest recommended total daily human ophthalmic dose); however, decreased fetal body weights and slightly delayed fetal skeletal development were observed. There was no evidence of teratogenicity when pregnant Cynomolgus monkeys were given oral doses as high as 100 mg/kg/day (approximately 4,300 times the highest recommended total daily human ophthalmic dose). An increased incidence of smaller fetuses was observed at 100 mg/kg/day.
Since there are no adequate and well-controlled studies in pregnant women MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no or limited amount of data from the use of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution in pregnant women. However, no effects on pregnancy are anticipated since the systemic exposure to moxifloxacin from topical ocular application is negligible.
Use in Lactation: It is unknown whether moxifloxacin/metabolites are excreted in human milk. Animal studies have shown excretion of low levels in breast milk after oral administration of moxifloxacin. However, at therapeutic doses of MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution no effects on the suckling child are anticipated.
Adverse Reactions
No serious ophthalmic or systemic adverse reactions related to MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution were reported.
Adverse reactions were generally mild and occurred at an incidence similar to placebo (vehicle). The most frequently reported event was transient ocular discomfort (burning/ stinging) reported at an incidence of 2.9%. Other reported events included headache, keratitis, ocular pain, ocular pruritus, ocular hyperemia, pharyngitis and subconjunctival hemorrhage which were reported at an incidence of 0.5 to 1.0%.
The following adverse reactions have been reported during clinical trials with [Moxifloxacin 5 mg/ml Eye Drops, Solution] and are classified according to the following convention: 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). Within each frequency-grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 1.)

Click on icon to see table/diagram/image

Additional adverse reactions identified from post-marketing surveillance include the following. Frequencies cannot be estimated from the available data. Within each System Organ Class adverse reactions are presented in order of decreasing seriousness. (See Table 2.)

Click on icon to see table/diagram/image
Drug Interactions
While drug-drug interaction studies have not been conducted with MOXIFLOXACIN hydrochloride (VIGAMOX*) Ophthalmic Solution, they have been performed with the oral product at such higher systemic exposure than are achieved by the topical ocular route. Unlike some other fluoroquinolones, no clinically significant drug-drug interactions between systemically administered moxifloxacin and itraconazole, theophylline, warfarin, digoxin, oral contraceptives, probenecid, ranitidine or glyburide have been observed. In vitro studies indicates that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19 or CYP1A2 indicating that moxifloxacin is unlikely to after the pharmacokinetics of drugs metabolized by these cytochrome P450 isozymes.
Storage
Store at a temperature not exceeding 30°C.
ATC Classification
J01MA14 - moxifloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
Ophth drops 5 mg/mL x 5 mL.
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