Lacrison T Ophthalmic Suspension 0.5%+0.3%

Lacrison T Ophthalmic Suspension 0.5%+0.3% Uses, Dosage, Side Effects, Food Interaction and all others data.

Loteprednol is a corticosteroid which is thought to act by the induction of phospholipase A2 inhibitory proteins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid.

Tobramycin is a member of aminoglycoside which shows bactericidal activity by inhibiting protein synthesis of bacteria.

Trade Name Lacrison T Ophthalmic Suspension 0.5%+0.3%
Generic Loteprednol Etabonate + Tobramycin
Weight 0.5%+0.3%
Type Ophthalmic Suspension
Therapeutic Class Ophthalmic steroid - antibiotic combined preparations
Manufacturer Beximco Pharmaceuticals Ltd.
Available Country Bangladesh
Last Updated: October 19, 2023 at 6:27 am
Lacrison T Ophthalmic Suspension 0.5%+0.3%
Lacrison T Ophthalmic Suspension 0.5%+0.3%

Uses

This 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, cyclitis. It is also used for chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies. This is also used for the treatment of post-operative inflammation following ocular surgery.

Lacrison T Ophthalmic Suspension 0.5%+0.3% is also used to associated treatment for these conditions: Dry Eye Syndrome (DES), Eye Pain, Ocular InflammationBacterial Peritonitis, Bone Infection, Cystic fibrosis, Pseudomonas aeruginosa infection, Eye Infections, Inflammation of the External Auditory Canal, Intra-Abdominal Infections, Lower respiratory tract infection bacterial, Meningitis, Bacterial, Ocular Inflammation, Septicemia gram-negative, Skin and Subcutaneous Tissue Bacterial Infections, Corticosteroid-responsive Disorder of the Ophthalmic, Ear infection-not otherwise specified caused by susceptible bacteria, Ocular bacterial infections, Recurrent Complicated Urinary Tract Infection, Steroid-responsive inflammation

How Lacrison T Ophthalmic Suspension 0.5%+0.3% 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 .

Tobramycin is a 4,6-disubstituted 2-deoxystreptamine (DOS) ring-containing aminoglycoside antibiotic with activity against various Gram-negative and some Gram-positive bacteria. The mechanism of action of tobramycin has not been unambiguously elucidated, and some insights into its mechanism rely on results using similar aminoglycosides. In general, like other aminoglycosides, tobramycin is bactericidal and exhibits both immediate and delayed killing, which are attributed to different mechanisms, as outlined below.

Aminoglycosides are polycationic at physiological pH, such that they readily bind to bacterial membranes ("ionic binding"); this includes binding to lipopolysaccharide and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acid and phospholipids within the cell membrane of Gram-positive bacteria. This binding displaces divalent cations and increases membrane permeability, which allows aminoglycoside entry. Additional aminoglycoside entry ("energy-dependent phase I") into the cytoplasm requires the proton-motive force, allowing access of the aminoglycoside to its primary intracellular target of the bacterial 30S ribosome. Mistranslated proteins produced as a result of aminoglycoside binding to the ribosome (see below) integrate into and disrupt the cell membrane, which allows more of the aminoglycoside into the cell ("energy-dependent phase II"). Hence, tobramycin and other aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modelling support this two-mechanism model.

Inhibition of protein synthesis was the first recognized effect of aminoglycoside antibiotics. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects, including inhibiting translation initiation and elongation and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation; mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.

Although direct mutation of the 16S rRNA is a rare resistance mechanism, due to the gene being present in numerous copies, posttranscriptional 16S rRNA modification by 16S rRNA methyltransferases (16S-RMTases) at the N7 position of G1405 or the N1 position of A1408 are common resistance mechanisms in aminoglycoside-resistant bacteria. These mutants also further support the proposed mechanism of action of aminoglycosides. Direct modification of the aminoglycoside itself through acetylation, adenylation, and phosphorylation by aminoglycoside-modifying enzymes (AMEs) are also commonly encountered resistance mutations. Finally, due to the requirement for active transport of aminoglycosides across bacterial membranes, they are not active against obligately anaerobic bacteria.

Dosage

Lacrison T Ophthalmic Suspension 0.5%+0.3% dosage

Shake well before use. Apply one drop into the conjunctival sac of the affected eye(s) every four to six hours. During the initial 24 to 48 hours, the dosing may be increased, to every one to two hours.

Side Effects

Increased intraocular pressure, burning and stinging upon instillation, vision disorders, discharge, itching, lacrimation disorder, photophobia, corneal deposits, ocular discomfort, eyelid disorder, and other unspecified eye disorders may occur. The incidence of non-ocular adverse events (headache) also reported.

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 .

Toxicity information regarding tobramycin is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as nephrotoxicity, ototoxicity, neuromuscular blockade, and respiratory failure/paralysis. Symptomatic and supportive measures are recommended; hemodialysis may help clear excess tobramycin. Accidental ingestion of tobramycin is unlikely to result in an overdose, as aminoglycosides are poorly absorbed in the gastrointestinal tract.

Poor gastrointestinal absorption is reflected in animal studies. When administered by the intraperitoneal or subcutaneous route, the LD50 for mice and rats ranges from 367-1030 mg/kg while the oral LD50 values are more than 7500 mg/kg.

Precaution

  • For ophthalmic use only.
  • If this product is used for 10 days or longer, intraocular pressure should be monitored.
  • Fungal infections of the cornea are particularly prone to develop coincidentally with long-term use of steroid topically.
  • Prolonged use may result in overgrowth of nonsusceptible organisms including fungi. If superinfection occurs, appropriate therapy should be initiated.
  • Cross-sensitivity to other aminoglycoside antibiotics may occur.

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.

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 .

Inhalation tobramycin had an apparent volume of distribution in the central compartment of 85.1 L for a typical cystic fibrosis patient.

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 .

Tobramycin administered by inhalation in cystic fibrosis patients showed greater variability in sputum as compared to serum. After a single 112 mg dose, the serum Cmax was 1.02 ± 0.53 μg/mL, which was reached in one hour (Tmax), while the sputum Cmax was 1048 ± 1080 μg/g. Comparatively, for a 300 mg dose, the serum Cmax was 1.04 ± 0.58 μg/mL, which was also reached within one hour, while the sputum Cmax was 737 ± 1028 μg/g. The systemic exposure (AUC0-12) was also similar between the two doses, at 4.6 ± 2.0 μg∙h/mL for the 112 mg dose and 4.8 ± 2.5 μg∙h/mL for the 300 mg dose. When tobramycin was administered over a four-week cycle at 112 mg twice daily, the Cmax measured one hour after dosing ranged from 1.48 ± 0.69 μg/mL to 1.99 ± 0.59 μg/mL.

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 .

Tobramycin has an apparent serum terminal half-life of ~3 hours following a single 112 mg inhaled dose in cystic fibrosis patients.

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 .

Inhaled tobramycin has an apparent serum clearance of 14.5 L/h in cystic fibrosis patients aged 6-58 years.

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 .

Tobramycin is primarily excreted unchanged in the urine.

Pregnancy & Breastfeeding use

Use in pregnancy: There are no adequate and well-controlled studies in pregnant women. Loteprednol Etabonate & Tobramycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in lactation: Caution should be exercised when Loteprednol Etabonate & Tobramycin is administered to a nursing mother.

Contraindication

Contraindicated in most viral diseases of the cornea and conjunctiva. Also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of Lacrison T Ophthalmic Suspension 0.5%+0.3% and to other corticosteroids.

Special Warning

Use in children: Safety and effectiveness in pediatric patients have not been established.

Acute Overdose

Symptoms: Nephrotoxicity, auditory and vestibular toxicity (e.g. dizziness, tinnitus, vertigo, loss of high-tone hearing acuity), neuromuscular blockade or resp failure.

Management: Initiate resuscitative measures if resp paralysis occurs. Ca salts may be given to reverse neuromuscular blockade. Haemodialysis or peritoneal dialysis will help remove drug serum levels.

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 four weeks after first opening of the bottle. Protect from freezing.

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