Noirmox L

Uses

Loteprednol etabonate is used for the treatment of steroid responsive 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
• Cyclitis

It is also used for the treatment of post-operative inflammation following ocular surgery.

Moxifloxacin is used for the treatment of adults (>18 years of age) with infections caused by susceptible strains of the designated microorganisms in the conditions listed below-

• Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus infuenzae or Moraxella catarrhalis.
• Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus infuenzae, Haemophilus parainfuenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus or Moraxella catarrhalis
• Community Acquired Pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains), Haemophilus infuenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae or Chlamydophilia pneumoniae.
• Uncomplicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogen.
• Complicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Enterobacter cloacae.
• Complicated Intra-Abdominal Infections including polymicrobial infections such as abscess caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron or Peptostreptococcus species.

Noirmox L is also used to associated treatment for these conditions: Dry Eye Syndrome (DES), Eye Pain, Ocular InflammationAcute Exacerbation of Chronic Bronchitis (AECB), Bacterial Conjunctivitis, Community Acquired Pneumonia (CAP), Plague, Postoperative Inflammatory Response, Sinusitis, Skin Infections, Ocular bacterial infections, Post-operative infection

How Noirmox L works

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 .

The bactericidal action of moxifloxacin results from inhibition of the enzymes 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.

Dosage

Noirmox L dosage

Shake the bottle vigorously before using

Steroid responsive disease treatment: Apply 1 to 2 drops of Loteprednolinto the conjunctival sac of the affected eye(s) four times daily. During the initial treatment within the first week, the dosing may be increased, up to 1 drop every hour, if necessary. Care should be taken not to discontinue therapy prematurely.

Post-Operative Inflammation: Apply 1 to 2 drops of Loteprednolinto the conjunctival sac of the operated eye(s) four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the post-operative period.

The dose of Moxifloxacin is 400 mg once every 24 hours. The duration of therapy depends on the type of infection as described bellow-

• In Acute Bacterial Sinusitis: Moxifloxacin 400 mg is given once daily for 10 days.
• In Acute Bacterial Exacerbation of Chronic Bronchitis: Moxifloxacin 400 mg is given once daily for 5 days.
• In Community Acquired Pneumonia: Moxifloxacin 400 mg is given once daily for 7-14 days.
• In Uncomplicated Skin & Skin Structure infections: Moxifloxacin 400 mg is given once daily for 7 days.
• In Complicated Skin & Skin Structure infections: Moxifloxacin 400 mg is given once daily for 7-21 days.
• In Complicated Intra-Abdominal infections: Moxifloxacin 400 mg is given once daily for 5-14 days.

Moxifloxacin 400 mg IV infusion can be administered intravenously for the entire treatment duration. Alternatively, therapy may be initial intravenous administration, followed by oral administration when clinically indicated. The recommended duration of treatment for the indication being treated should not be exceeded. The solution for infusion should be infused intravenously over 60 minutes.

Side Effects

Local reactions (e.g. blurred vision, burning, itching, dry eye), photophobia, headache, rhinitis, pharyngitis. Prolonged use may increase IOP, which may be associated with possible development of glaucoma and infrequent optic nerve damage; posterior sub-capsular cataract formation and perforation of the globe where there is thinning of the cornea or sclera.

The following one or more side effects may be observed: tendinopathy and tendon rupture, QT prolongation, hypersensitivity reactions, Clostridium difficile-associated diarrhea, peripheral neuropathy, photosensitivity, phototoxicity etc.

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 .

Symptoms of overdose include CNS and gastrointestinal effects such as decreased activity, somnolence, tremor, convulsions, vomiting, and diarrhea. The minimal lethal intravenous dose in mice and rats is 100 mg/kg.

Precaution

• Shake the bottle well before use
• Patients should be advised not to allow the dropper tip to touch the eye, eyelid, fingers, or any other surface to prevent contamination
• Patients should be advised not to wear soft contact lenses when using this drug
• If this product is used for 10 days or longer, intraocular pressure should be monitored.
• The possibility of fungal infections of the cornea should be considered after long-term steroid dosing
• The use of steroids may delay wound healing.

Moxifloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Moxifloxacin should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon.

Interaction

Since Loteprednol Etabonate is not detected in plasma following the topical administration, it is not expected to affect the pharmacokinetics of systemically administered medicinal products.

No quinolone should be co-administered with any solution containing multivalent cations (e.g. magnesium) through the same intravenous line. Antacids, iron and adsorbents reduce absorption of Moxifloxacin. NSAID may increase the risk of CNS stimulation. Warfarin may increase the risk of bleeding.

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 .

• 1.7 to 2.7 L/kg

Elimination Route

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 .

Well absorbed from the gastrointestinal tract. Absolute oral bioavailability is approximately 90%. Food has little effect on absorption.

Half Life

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 .

11.5-15.6 hours (single dose, oral)

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 .

• 12 +/- 2 L/hr

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 .

Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces).

Pregnancy & Breastfeeding use

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.

Pregnancy Category C. Moxifloxacin is not recommended during pregnancy & lactation.

Contraindication

Loteprednol, as with other ophthalmic corticosteroids, is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures.

Loteprednol is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of Loteprednol Etabonate and to other corticosteroids.

Moxifloxacin is contraindicated in persons with a history of hypersensitivity to Moxifloxacin or any member of the quinolone class of antimicrobial agents and any component of this formulation.

Special Warning

Elderly: No adjustment of dosage is required in the elderly.

Children: Efficacy and safety of Moxifloxacin IV infusion in children and adolescent have not been established.

Acute Overdose

In the events of an acute overdose, the stomach should be emptied. The patient should be kept under observation and appropriate hydration should be maintained.

Storage Condition

Protect from light. Store in cool & dry place. Keep out of the reach of children. Do not use more than 4 weeks after opening. Shake well before using.

Store between 15 to 30° C. Protect from light and moisture. Keep away from reach of children.

Innovators Monograph

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