Megacom ™

Moxifloxacin & Ketorolac Tromethamine Ophthalmic Solution. Megacom Ophthalmic Solution is indicated for the reduction of post-operative inflammatory conditions of the eye.

 

Trade Name:

Megacom

Moxifloxacin & Ketorolac Tromethamine Ophthalmic Solution

Composition:

Each ml contains

Moxifloxacin Hydrochloride BP equivalent to Moxifloxacin 5.0 mg Ketorolac Tromethamine IP 5.0 mg

Auxiliary Matter:

Boric acid, Sodium chloride, Octoxynol 40, Disodium edetate, Sodium hydroxide and/or Hydrochloric acid (to adjust pH), Water for injection.

Dosage Form:

Eye Drops

Introduction:

Megacom Ophthalmic Solution is indicated for the reduction of post-operative inflammatory conditions of the eye.

Dosage and Method of Administration:

Instill one drop three times a day in the affected eye(s). The frequency of instillation of drops and the duration of treatment will vary depending on the severity of the underlying condition and the response to the treatment.

The dropper tip should not be allowed to touch any surface since this may contaminate the solution. If irritation persists or increases, the use should be discontinued.

Pharmacological Properties:

Clinical Pharmacology

Megacom Ophthalmic Solution combines moxifloxacin, an 8-methoxy fluroquinolone antibiotic and ketorolac tromethamine, a non-steroidal anti-inflammatory drug, intended for topical ophthalmic use.

Mechanism of Action:

The antibacterial action 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 key role in the partitioning of the chromosomal DNA during bacterial cell division.

The mechanism of action of 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 aforementioned classes of antibiotics. Cross resistance has been observed between systemic moxifloxacin and some other quinolones.

In vitro resistance to moxifloxacin develops via multiple step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between 1.8×10-9 to < 1×10-11 for gram-positive bacteria.

Moxifloxacin has been shown to be active against most strains of the aerobic gram-positive microorganisms including Cornyebacterium species*,Micrococcus luteus*, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri*, Streptococcus pneumoniae, Streptococcus viridans group; aerobic gram-negative microorganisms including Acinetobacter lwoffii*, Haemophilus influenzae, Haemophilus parainfluenzae*; and other microorganisms including Chlamydia trachomatis, both in vitro and in clinical infections.

*Efficacy for this organism was studied in fewer than 10 infections.

Ketorolac tromethamine is a non-steroidal anti-inflammatory drug which when administered systemically has demonstrated analgesic, anti-inflammatory, and antipyretic activities. Ketorolac tromethamine inhibits the cyclooxygenase enzyme essential for biosynthesis of prostaglandins. Ketorolac tromethamine has been shown to reduce prostaglandin levels in the aqueous humor after topical ophthalmic administration. Ketorolac tromethamine given systemically does not cause pupil constriction. Results from clinical studies indicate that ketorolac tromethamine has no significant effect on intraocular pressure; however, changes in intraocular pressure may occur following cataract surgery.

Pharmacokinetics:

Moxifloxacin Hydrochloride: Plasma concentrations of moxifloxacin were measured in healthy adult male and female subjects who received bilateral topical ocular doses of moxifloxacin ophthalmic solution 3 times a day. The mean steady state Cmax (2.7ng/mL) and estimated daily exposure AUC (45ng.hr/ml) values were 1,600 and 1000 times lower than the mean Cmax and AUC reported after therapeutic 400 mg oral doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.

Ketorolac tromethamine: One drop of 0.5% ketorolac tromethamine ophthalmic solution was instilled into one eye and one drop of vehicle into the other eye, TID in 26 normal subjects. Only 5 of 26 subjects had a detectable amount of ketorolac in their plasma (range 10.7 to 22.5ng/mL) at day 10 during topical ocular treatment. When ketorolac tromethamine 10 mg is administered systemically every 6 hours, peak plasma levels at steady state are around 960ng/mL.

Warnings and Precautions:

FOR EXTERNAL USE ONLY. NOT FOR INJECTION

Moxifloxacin ophthalmic solution should not be injected subconjunctivally; nor should it be introduced directly into the anterior chamber of eye

Use of moxifloxacin ophthalmic solution should be discontinued immediately at the first sign of a rash or allergic reaction. 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 oedema), 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 antiinfectives, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. 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.

There is the potential for cross-sensitivity to aspirin, phenylacetic acid derivatives, and other non-steroidal anti-inflammatory agents. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs. With some non-steroidal anti-inflammatory drugs, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied non-steroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.

All topical non-steroidal anti-inflammatory drugs (NSAIDs) may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. In common with other anti-inflammatory drugs ketorolac may mask the usual signs of infection.

Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Post marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients.

Post marketing experience with topical NSAIDs also suggests that use more than 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events. It is recommended that ketorolac tromethamine ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

Contraindications:

  • In patients with previously demonstrated hypersensitivity to ketorolac, moxifloxacin, other quinolones or any other ingredient in the formulation.
  • The potential exists for cross-sensitivity to aspirin, and other non-steroidal anti-inflammatory drugs. This drug is contraindicated in individuals who have previously exhibited sensitivities to these drugs.

Drug Interactions:

Drug drug interaction studies have not been conducted with moxifloxacin ophthalmic solution. In vitro studies indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19 or CYP1A2 indicating that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these cytochrome P450 isozymes.

Ketorolac tromethamine has been safely administered with systemic and ophthalmic medications such as antibiotics, sedatives, beta blockers, carbonic anhydrase inhibitors, miotics, mydriatics and cycloplegics. Ketorolac tromethamine may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical corticosteroids may increase the potential for healing problems. If ketorolac tromethamine is used concomitantly with other topical eye medications there must be an interval of at least five minutes between the two medications.

Undesirable Effects:

Moxifloxacin: The most frequently reported ocular adverse events occurred in approximately 1-6% of patients were conjunctivitis, decreased visual acuity, dry eye, keratitis, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, subconjunctival hemorrhage and tearing. Nonocular adverse events reported at a rate of 1-4% were fever, increased cough, infection, otitis media, pharyngitis, rash and rhinitis.

Ketorolac tromethamine: The most frequently reported adverse events reported up to 40% of patients are transient stinging and burning on instillation.

Other adverse events occurring approximately 1 to10% of the time during treatment with ketorolac tromethamine ophthalmic solution included allergic reactions, corneal edema, iritis, ocular inflammation, ocular irritation, superficial keratitis and superficial ocular infections.

Other adverse events reported rarely with the use of ketorolac tromethamine ophthalmic solution included corneal infiltrates, corneal ulcer, eye dryness, headaches, and visual disturbance (blurry vision), hypersensitivity, eye and/or eyelid oedema, eye pruritus, conjunctival/ocular hyperaemia and increased lacrimation was also reported with the use of ketorolac tromethamine ophthalmic solution.

The following events have been identified during postmarketing use of ketorolac tromethamine ophthalmic solution 0.5% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to topical ketorolac tromethamine ophthalmic solution 0.5% or a combination of these factors, include corneal erosion, corneal perforation, corneal thinning and epithelial breakdown.

Use in Special Populations:

Pregnant women:

There are no adequate and well controlled studies in pregnant women with moxifloxacin or ketorolac. Megacom should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the known effects of prostaglandin inhibiting drugs on the fetal cardiovascular system (closure of ductus arteriosus), the use of Megacom during late pregnancy should be avoided.

Lactating women:

Moxifloxacin has not been measured in human milk, although it can be presumed to be excreted in human milk. Ketorolac has been detected in human milk at low levels. Caution should be exercised when Megacom is administered to a nursing mother.

Geriatric Population : No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Shelf Life:

2 years

Packaging Information:

Product is packed in a 5 ml white plastic bottle with a plastic nozzle pre sterilized and white plastic cap.

Incompatibilities:

None reported.

Storage and Handling Instructions:

Store in a cool, dark place. Protect from light. Keep away from reach of children. Use this solution within one month of opening the vial.

Marketed by: PROVIS

A division of Promed