PHARMACODYNAMIC PROPERTIES

MOXIFLOXACIN: 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. 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. In vitro resistance to Moxifloxacin develops via multiple-step mutations.

Moxifloxacin has been shown to be active against most strains of the following microorganisms:

DEXAMETHASONE is a highly potent and long-acting glucocorticoid. It has an approximately 7 times greater anti-inflammatory potency than prednisolone, another commonly prescribed corticosteroid.

The actions of corticosteroids are mediated by the binding of the corticosteroid molecules to receptor molecules located within sensitive cells. Corticosteroid receptors are present in human trabecular meshwork cells and in rabbit iris ciliary body tissue.

Corticosteroids will inhibit phospholipase A2 thereby preventing the generation of substances which mediate inflammation, for example, prostaglandins. Corticosteroids also produce a marked, though transient, lymphocytopenia. This depletion is due to redistribution of the cells, the T lymphocytes being affected to a greater degree than the B lymphocytes. Lymphokine production is reduced, as is the sensitivity of macrophages to activation by lymphokines. Corticosteroids also retard epithelial regeneration, diminish post-inflammatory neo-vascularisation and reduce towards normal levels the excessive permeability of inflamed capillaries.

PHARMACOKINETIC PROPERTIES

MOXIFLOXACIN: Following application to both eyes of Moxifloxacin 0.5% ophthalmic solution in healthy adults, the mean steady-state Cmax (2.7 ng/mL) and the estimated AUC (45 ng hr/mL) values were 1,600 and 1,000 times lower respectively, than the values reported after therapeutic 400 mg oral doses of moxifloxacin.

DEXAMETHASONE: When given topically to the eye, Dexamethasone is absorbed into the aqueous humour, cornea, iris, choroid, ciliary body and retina. Systemic absorption occurs but may be significant only at higher dosages or in extended paediatric therapy.

Up to 90% of Dexamethasone is absorbed when given by mouth; peak plasma levels are reached between 1 and 2 hours after ingestion and show wide individual variations. Dexamethasone sodium phosphate is rapidly converted to Dexamethasone within the circulation. Up to 77% of dexamethasone is bound to plasma proteins, mainly albumin. This percentage, unlike cortisol, remains practically unchanged with increasing steroid concentrations. The mean plasma half life of Dexamethasone is 3.6 + 0.9h.

Tissue distribution studies in animals show a high uptake of Dexamethasone by the liver, kidney and adrenal glands; a volume of distribution has been quoted as 0.58 /kg. In man, over 60% of circulating steroids are excreted in the urine within 24 hours, largely as unconjugated steroid.

Dexamethasone also appears to be cleared more rapidly from the circulation of the foetus and neonate than in the mother; plasma Dexamethasone levels in the foetus and the mother have been found in the ratio of 0.32:1

THERAPEUTIC INDICATIONS

It is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial ocular Infection exists, The combination can also be used for post-operative inflammation and any other ocular inflammation associated with infection.

APPLICATION AND ADMINISTRATION

One or two drops instilled into the conjunctival sac(s), every 4 to 6 hours, During the initial 24 to 48 hours, the dosage may be increased to 1 or 2 drops every two hours. Frequency must be decreased gradually or warranted by improvement in clinical signs. Care should be taken not to discontinue the therapy prematurely. Use the solution within one month after opening the container.

NOT FOR INJECTION. FOR EXTERNAL USE ONLY.

CONTRAINDICATIONS

It is contraindicated in epithelial herpes simplex keratitis (Dendritic keratitis), vaccinia, varicella, and in many other viral diseases of the conjunctiva and cornea, Mycobacterial infection of the eye and fungal diseases of ocular structures and in individuals hypersensitive to any of the components of the medication.

SPECIAL WARNINGS AND PRECAUTIONS

Prolonged use of steroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and posterior subcapsular cataract formation.

DRUG INTERACTIONS

The risk of increased intraocular pressure associated with prolonged corticosteroid therapy may be more likely to occur with concomitant use of anticholinergics, especially atropine and related compounds, in patients predisposed to acute angle closure.

The risk of corneal deposits or corneal opacity may be more likely to occur in patients presenting with compromised cornea and receiving polypharmacy with other phosphate containing eye medications.

The following drug interactions are possible, but are unlikely to be of clinical significance, following the use of moxifloxacin and dexamethasone solution in the eye.

The therapeutic efficacy of Dexamethasone may be reduced by phenytoin, phenobarbitone, ephedrine and rifampicin.

Glucocorticoids may increase the need for salicylates as plasma salicylate clearance is increased.

PREGNANCY AND LACTATION

If you are pregnant or breast feeding, think you may be pregnant, or are planning to have a baby, you should ask your doctor or eye specialist for advice before taking this medicine. There is insufficient information available to determine the potential harmful effects on pregnancy. Moxifloxacin and Dexamethasone should not be used during pregnancy and breast-feeding unless considered appropriate by your doctor or eye specialist.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Your eyesight may become blurred for a short time following the use of Moxifloxacin and Dexamethasone. You must not drive or operate hazardous machinery until your eyesight has returned to normal.

UNDESIRABLE EFFECTS

The most frequently reported drug-related undesirable effects seen with Moxifloxacin are conjunctival irritation, increased lacrimation, keratitis and papillary conjunctivitis.

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 and Dexamethasone in a single container is too small to induce adverse effects after accidental ingestion.

STORAGE

Store below 25°C. Protect from light & moisture. Do not freeze.

PRESENTATION

Vigoquin-DX Eye Drops is available in a 5 ml pack.