Loteprednol Etabonate + Gatifloxacin

Uses

Each ml sterile ophthalmic suspension contains:

• Active substances: Loteprednol Etabonate 5 mg and Gatifloxacin 3 mg.
• Preservative: Benzalkonium Chloride 0.05 mg.

This ophthalmic suspension is used for steroid-responsive inflammatory ocular conditions for which a corticosteroid is used and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists. Ocular steroids are used for inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, and cyclitis. It is also used for the treatment of post-operative inflammation following ocular surgery.

Loteprednol Etabonate + Gatifloxacin is also used to associated treatment for these conditions: Bacterial Conjunctivitis, Ocular Infections, Irritations and InflammationsDry Eye Syndrome (DES), Eye Pain, Ocular Inflammation

How Loteprednol Etabonate + Gatifloxacin works

The bactericidal action of Gatifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.

Corticosteroids like loteprednol etabonate inhibit the inflammatory response to a variety of inciting agents and likely delay or slow healing . They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation that are commonly associated with inflammation . While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor-dependent modulation of inflammation are not clearly established . Moreover, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms . In particular, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins . It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid . Arachidonic acid is released from membrane phospholipids by phospholipase A2 .

The use of LE subsequently treats post-operative inflammation and pain following ocular surgery by managing the prostaglandin release, recruitment and travel of neutrophils and macrophages, and production of other inflammatory mediators that are intrinsically associated with the physical trauma of surgery .

Dosage

Loteprednol Etabonate + Gatifloxacin dosage

Apply one or two drops of sterile ophthalmic suspension into the conjunctival sac of the affected eye(s) every four to six hours. During the initial 24 to 48 hours, the dosing maybe increased, to every one to two hours. Frequency should be decreased gradually as warranted by improvement in clinical signs. Care should be taken not to discontinue therapy prematurely.

Gatifloxacin can be administered without regard to food.

Side Effects

Adverse reactions have occurred with steroid/anti-infective combination drugs which can be attributed to the steroid component or the anti-infective component, or the combination. Reactions associated with ophthalmic steroids include elevated IOP, which may be associated with infrequent optic nerve damage, visual acuity and field detects, posterior sub capsular cataract formation, delayed wound healing, and secondary ocular infections from pathogens including herpes simplex, and perforation of the globe where there is thinning of cornea or sclera. The most frequently reported adverse effects for gatifloxacin in the overall study population were conjunctival irritation, increased lacrimation, keratitis and papillary conjunctivitis. These events occurred in approximately 5-10% of patients. Other reported reactions occurring in 1-4% of patients were chemosis, conjunctival hemorrhage, dry eye, eye discharge, eye irritation, eye pain, eyelid edema, headache, red eye, reduced visual acuity and taste disturbance. Redness was the most commonly observed adverse event occurring in 6%. Itching, discharge photophobia and blurred vision were seen in less than 2% cases.

Toxicity

The most common adverse drug reactions reported during clinical trials for the medication were eye pain and posterior capsular opacification, both of which may also be the consequence of the very surgical procedures performed on the eye(s) .

The agent is not absorbed systemically following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to the drug .

The medication is not absorbed systemically by the mother following topical ophthalmic administration, and breastfeeding is not expected to result in exposure of the child to the agent .

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma thymidine kinase (tk) assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay .

Overdose is not expected to be likely to occur after ocular administration .

Precaution

The preparation should not be injected sub conjunctively, nor should it be introduced directly into the anterior chamber of the eye. If this product is used for 10 days or longer, intraocular pressure should be monitored. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. If redness or itching becomes aggravated, the patient should be advised to consult a physician. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling it before they insert their contact lenses.

Interaction

No drug interaction is reported yet. If several medicines are to be administered to the eye, there should be an interval of at least 5 minutes between each application.

Volume of Distribution

The only data available regarding the volume of distribution of loteprednol etabonate (LE) is the volume of distribution the agent demonstrated when administered to dogs - a value of 3.7 L/kg . It has been shown, however, that the topical ocular administration of LE distributes preferentially into the cellular components of blood .

Elimination Route

Well absorbed from the gastrointestinal tract after oral administration with absolute bioavailability of gatifloxacin is 96%

Loteprednol etabonate (LE) demonstrates good ocular permeation properties as it is lipid soluble, allowing the agent to penetrate into cells with relative ease .

Results from the ocular administration of loteprednol in normal, healthy volunteers have shown that there are low or undetectable concentrations of either unchanged material or its metabolite . Following twice-daily unilateral topical ocular dosing of LE for 14 days in healthy subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (1 ng/mL) at all time points . These finds suggest that limited, if any, systemic absorption of LE occurs .

Half Life

7-14 hours

The terminal half-life of loteprednol etabonate as determined when administered intravenously at a dose of 5 mg/kg in the dog animal model is 2.8 hours .

Clearance

Loteprednol etabonate was slowly hydrolyzed in liver at clearance rates of 0.21 +/- 0.04 and 2.41 +/- 0.13 ml/h/kg in the liver and plasma, respectively .

Elimination Route

Following systemic administration to rats, loteprednol etabonate is eliminated primarily via the biliary/faecal route, with most of the dose eliminated in the form of the metabolite, PJ-90 .

Pregnancy & Breastfeeding use

Pregnancy: Gatifloxacin should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

Lactation: It is not known whether Gatifloxacin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when gatifloxacin is administered to a nursing woman.

It is Pregnancy Category C. It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk.

Contraindication

This sterile ophthalmic suspension is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex and also in mycobacterial infection of the eye and fungal diseases of ocular structures. It is also contraindicated in known hypersensitivity to any of the ingredients of Loteprednol Etabonate + Gatifloxacin. It is also contraindicated in patients with a history of hypersensitivity to other quinolones, acetylsalicylic acid and other no steroidal inflammatory medicines.

Special Warning

Renal Impaired patient:

• Creatinine Clearance 40 mL/min: 400 mg every day.
• Creatinine Clearance < 40 mL/min: 400 mg 200 mg every day.

Dialysis patients:

• Hemodialysis: 400 mg 200 mg every day.
• Continuous peritoneal dialysis: 400 mg 200 mg every day.

Pediatric use: The safety and effectiveness of Gatifloxacinacin in pediatric populations (<18 years of age) have not been established.

Acute Overdose

Gatifloxacin exhibits a low potential for acute toxicity in animal studies. In the event of acute oral overdose, the stomach should be emptied by inducing vomiting or by gastric lavage. The patient should be carefully observed (including ECG monitoring) and given symptomatic and supportive treatment. Adequate hydration should be maintained.

Storage Condition

Store at room temperature & protect from light. Do not touch dropper tip to any surface. It is desirable that the contents should not be used one month after first opening of the bottle. Protect from freezing.

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