MOXICIP Eye Ointment (Moxifloxacin 0.5%)

Transcription

1 Published on: 19 Sep 2014 MOXICIP Eye Ointment (Moxifloxacin 0.5%) Composition Moxifloxacin 0.5% (5 mg/ml) Dosage Form Ophthalmic Ointment Pharmacology Pharmacodynamics Moxifloxacin is a member of the fluoroquinolone class of anti-infective drugs. Moxifloxacin is an 8-methoxy fluoroquinolone with a diazabicyclononyl ring at the C7 position. The antibacterial action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, aminoglycosides, or tetracyclines. Therefore, moxifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to moxifloxacin. There is no cross-resistance between moxifloxacin and the aforementioned classes of antibiotics. Cross resistance has been observed between systemic moxifloxacin and some other quinolones. Mechanisms of Resistance: Resistance to fluoroquinolones, including moxifloxacin, occurs generally by chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, moxifloxacin resistance can be due to mutations in mar (multiple antibiotic resistance) and the qnr (quinolone resistance) gene systems. Resistance is also associated with expression of bacteria efflux proteins and inactivating enzymes. Cross-resistance with beta-lactams, macrolides and aminoglycosides is not expected due to differences in mode of action. In vitro resistance to moxifloxacin develops via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between to < for Gram-positive bacteria. Susceptibility testing breakpoints There are no pharmacological data correlated with clinical outcome for moxifloxacin administered as a topical agent. As a result, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) suggests the following epidemiological cut-off values (ECOFF mg/l) derived from MIC distribution curves to indicate susceptibility to topical moxifloxacin. Corynebacterium Staphylococcus aureus ND

2 Staphylococcus, coag-neg. Streptococcus pneumoniae Streptococcus pyogenes Streptococcus, viridans group Enterobacter spp. Haemophilus influenzae Klebsiella spp. Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Pseudomonas aeruginosa Serratia marcescens 0.5 mg/l 0.5 mg/l 0.5 mg/l mg/l mg/l 4 mg/l 1 mg/l The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of moxifloxacin in at least some types of infections is questionable. Moxifloxacin has been shown to be active against most strains of the following microorganisms: Aerobic Gram-positive microorganisms Corynebacterium species 1 including Corynebacterium diphtheriae Micrococcus luteus 1 Staphylococcus aureus (methicillin susceptible) Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus warneri 1 Streptococcus pyogenes Streptococcus pneumoniae Streptococcus viridans group Aerobic Gram-negative microorganisms Acinetobacter lwoffii 1 Haemophilus influenzae Haemophilus parainfluenzae 1 Enterobacter cloacae Klebsiella oxytoca Moraxella catarrhalis Serratia marcescens Anaerobic micro-organisms Propionibacterium acnes Other microorganisms

3 Chlamydia trachomatis 1 Efficacy for this organism was studied in fewer than 10 infections. Species for which acquired resistance may be a problem Aerobic Gram-positive microorganisms: Staphylococcus aureus (methicillin resistant) Staphylococcus, coagulase-negative species (methicillin resistant) Aerobic Gram-negative microorganisms: Neisseria gonorrhoeae Other microorganisms: None Inherently resistant organisms Aerobic Gram-negative microorganisms: Pseudomonas aeruginosa Other microorganisms: None The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of moxifloxacin in treating ophthalmological infections due to these microorganisms have not been established in adequate and well-controlled trials. The following organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. The list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections. Moxifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2 microgram/ml or less (systemic susceptible breakpoint) against most ( 90%) strains of the following ocular pathogens. Aerobic Gram-positive microorganisms Listeria monocytogenes Staphylococcus saprophyticus Streptococcus agalactiae Streptococcus mitis Streptococcus pyogenes Streptococcus Group C, G and F Aerobic Gram-negative microorganisms Acinetobacter baumannii Acinetobacter calcoaceticus Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Proteus mirabilis

4 Proteus vulgaris Pseudomonas stutzeri Anaerobic microorganisms Clostridium perfringens Fusobacterium species Prevotella species Propionibacterium acnes Other microorganisms Chlamydia pneumoniae Legionella pneumophila Mycobacterium avium Mycobacterium marinum Mycoplasma pneumoniae Pharmacokinetics Plasma concentrations of moxifloxacin were measured in healthy adult male and female subjects who received bilateral topical ocular doses of moxifloxacin three times a day. The mean steady-state C max (2.7 ng/ml) and estimated daily exposure AUC (45 ng hr/ml) values were 1,600 and 1,000 times lower than the mean C max and AUC reported after therapeutic 400 mg oral doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours. Indications Moxifloxacin ophthalmic ointment is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Aerobic Gram-positive Microorganisms Corynebacterium species 2 Micrococcus luteus 2 Staphylococcus aureus Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus warneri 2 Streptococcus pneumoniae Streptococcus viridans group Aerobic Gram-negative Microorganisms Acinetobacter lwoffii 2 Haemophilus influenzae Haemophilus parainfluenzae 2 Other Microorganisms Chlamydia trachomatis 2 Efficacy for this organism was studied in fewer than 10 infections. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

5 Dosage And Administration The recommended dosage regimen for the treatment of bacterial conjunctivitis is: Apply half-inch ribbon three times a day on the first two days. For the next five days apply half-inch ribbon two times a day. Contraindications Moxifloxacin ophthalmic ointment is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication. Warnings And Precautions General In patients receiving systemically administered quinolones, including moxifloxacin, 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 edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to moxifloxacin occurs, discontinue use of the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated. 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. Tendon inflammation and rupture may occur with systemic fluoroquinolone therapy including moxifloxacin, particularly in older patients and those treated concurrently with corticosteroids. Following ophthalmic administration of moxifloxacin ophthalmic solution, plasma concentrations of moxifloxacin are much lower than after therapeutic oral doses of moxifloxacin, however, caution should be exercised and treatment with moxifloxacin ophthalmic solution should be discontinued at the first sign of tendon inflammation. Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis. Moxifloxacin should not be used for the prophylaxis or empiric treatment of gonococcal conjunctivitis, including gonococcal ophthalmia neonatorum, because of the prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae. Patients with eye infections caused by Neisseria gonorrhoeae should receive appropriate systemic treatment. Data are very limited to establish efficacy and safety of moxifloxacin in the treatment of conjunctivitis in neonates. Therefore, use of this medicinal product to treat conjunctivitis in neonates is not recommended. Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition, e.g. systemic treatment in cases caused by Chlamydia trachomitis or Neisseria gonorrhoeae. The medicinal product is not recommended for the treatment of Chlamydia trachomatis in patients less than 2 years of age as it has not been evaluated in such patients. Patients older than 2 years of age with eye infections caused by Chlamydia trachomitis should receive appropriate systemic treatment. Drug Interactions Drug-drug interaction studies have not been conducted with MOXICIP ophthalmic ointment. In vitro studies indicate that

6 moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2 indicating that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by this cytochrome P450 isozymes. Given the low systemic concentration of moxifloxacin following topical ocular administration of the medicinal product, drug interactions are unlikely to occur. Pregnancy Pregnancy Category C Since there are no adequate and well-controlled studies in pregnant women, moxifloxacin ophthalmic ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Lactation Moxifloxacin has not been measured in human milk, although it can be presumed to be excreted in human milk. Caution should be exercised when moxifloxacin ophthalmic ointment is administered to a lactating female. Paediatric Use The safety and effectiveness of moxifloxacin in infants below 1 year of age have not been established. There is no evidence that the ophthalmic administration of moxifloxacin has any effect on weight bearing joints, even though oral administration of some quinolones has been shown to cause arthropathy in immature animals. Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger patients. Effects on Ability to Drive and Use Machines Moxifloxacin has no or negligible influence on the ability to drive and use machines, however, as with any eye drops, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient should wait until their vision clears before driving or using machinery. Undesirable Effects Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most frequently reported ocular adverse events were conjunctivitis, decreased visual acuity, dry eye, keratitis, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, subconjunctival hemorrhage, and tearing. These events occurred in approximately 1-6% of patients. Non-ocular adverse events reported at a rate of 1-4% were fever, increased cough, infection, otitis media, pharyngitis, rash, and rhinitis. In clinical studies involving 2,252 patients, moxifloxacin ophthalmic solution was administered up to 8 times a day, with 1,900 of these patients receiving treatment 3 times daily. The overall safety population that received the medicinal product consisted of 1,389 patients from the United States and Canada, 586 patients from Japan and 277 patients from India. No serious ophthalmic or systemic undesirable effects related to the medicinal product were reported in any of the clinical studies. The most frequently reported treatment-related undesirable effects with the medicinal product were eye irritation and eye pain, occurring at an overall incidence of 1 to 2%. These reactions were mild in 96% of those patients who experienced them, with only 1 patient discontinuing therapy as a result. The following undesirable effects were assessed to be treatment-related 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

7 <1/1000), or very rare (<1/10,000) or not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in decreasing order of seriousness. Table 1: Undesirable effects System Organ Classification Blood and lymphatic system Immune system Nervous system Eye Frequency Uncommon Common Uncommon Adverse reactions haemoglobin decreased hypersensitivity headache paresthesia dizziness eye pain, eye irritation punctate keratitis, dry eye, conjunctival haemorrhage, ocular hyperaemia, eye pruritus, eyelid oedema, ocular discomfort, corneal epithelium defect, corneal disorder, conjunctivitis, blepharitis, eye swelling, conjunctival oedema, vision blurred, visual acuity reduced, asthenopia, erythema of eyelid endophthalmitis, ulcerative keratitis, corneal erosion, corneal abrasion, intraocular pressure increased, corneal opacity, corneal infiltrates, corneal deposits, eye allergy, keratitis, corneal oedema, photophobia, eyelid oedema, lacrimation increased, eye discharge, foreign body sensation in eyes Cardiac palpitations Respiratory, thoracic and mediastinal Gastrointestional Hepatobiliary Skin and subcutaneous tissue Uncommon nasal discomfort, pharyngolaryngeal pain, sensation of foreign body (throat) dyspnoea dysgeusia vomiting nausea alanine aminotransferase increased, gammaglutamyltransferase increased erythema, rash, pruritus, urticaria Ruptures of the shoulder, hand, Achilles, or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving systemic fluoroquinolones. Studies and post marketing experience with systemic quinolones indicate that a risk of these ruptures may be increased in patients receiving corticosteroids, especially geriatric patients and in tendons under high stress, including Achilles tendon.

8 Paediatric Population In clinical trials, topical moxifloxacin 0.5% has shown to be safe in paediatric patients, including neonates. In patients under 18 years old, the two most frequent adverse reactions were eye irritation and eye pain, both occurring at an incidence rate of 0.9%. Based on data from clinical trials involving paediatric patients, including neonates, the type and severity of adverse reactions in the paediatric population are similar to those in adults. If you experience any side-effects, talk to your doctor or pharmacist or write to You can also report side effects directly via the national pharmacovigilance program of India by calling on By reporting side-effects, you can help provide more information on the safety of this product. Overdosage The limited holding capacity of the conjunctival sac for ophthalmic products practically precludes any overdosing of the medicinal product. The total amount of moxifloxacin in a single container is too small to induce adverse effects after accidental ingestion. Incompatibility Not applicable Shelf-Life 24 months Storage And Handling Instructions Store in a cool place Packaging Information MOXICIP Eye Ointment: Tube of 5gm Information For Patients Avoid contaminating the applicator tip with material from the eye, fingers or other source. Systemically administered quinolones including moxifloxacin have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction. Last Updated: November 2018 Last Reviewed: November 2018 MOXICIP Eye Ointment Source URL: