Econophen G

Uses

Blepharitis, blepharoconjunctivitis, conjunctivitis, dacryocystitis, keratitis, keratoconjunctivitis, acute meibomianitis, and corneal ulcers caused by susceptible organisms. Otorrhea associated with external otitis, chronic suppurative otitis media or subacute purulent otitis media; or postoperative otorrhea, such as that following fenestration, mastoidectomy or tympanoplasty.

Gentamicin cream is used for the topical treatment of the primary and secondary bacterial infections of the skin caused by the organisms sensitive to Gentamicin. Gentamicin may clear infections that have not responded to other topical antibiotics.

is used for the relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses including atopic dermatitis, contact dermatitis, eczematous dermatitis, neurodermatitis, seborrheic dermatitis, insect bites, lichen simplex chronicus, exfoliative dermatitis, stasis dermatitis, nummular eczema, psoriasis and pruritus ani and vulvae.

Econophen G is also used to associated treatment for these conditions: Bacterial Conjunctivitis, Bacterial Infections, Bacterial Peritonitis, Bacterial dacryocystitis, Blepharoconjunctivitis, Central Nervous System Infections, Conjunctivitis allergic, Corneal infection, Dermatitis infected, Ecthyma, Eczematous dermatitis infected, Folliculitis, Furunculosis, Gram-negative enteric bacilli neonatal sepsis, Impetigo contagious, Inflammation, Keratitis bacterial, Keratoconjunctivitis, Meibomianitis, Meningitis, Bacterial, Ocular Inflammation, Pustular Psoriasis (PP), Pustular acne, Pyoderma Gangrenosum, Seborrheic Dermatitis, Septicemia gram-negative, Skin Infections, Skin Infections, Bacterial, Skin and Subcutaneous Tissue Bacterial Infections, Sycosis barbae, Bacterial blepharitis, Bacterial corneal ulcers, Bacterial dermatoses, Complicated Bacterial Urinary Tract Infections, Complicated Respiratory tract infection bacterial, Corticosteroid-responsive dermatoses, Ocular bacterial infections, Severe Endocarditis enterococcal, Severe Infection Pseudomonas aeruginosa, Severe Staphylococcal infectionAcne, Acne Vulgaris, Acute Gouty Arthritis, Allergic Contact Dermatitis, Allergic Rhinitis (AR), Allergy Skin, Alopecia Areata (AA), Ankylosing Spondylitis (AS), Asthma, Atopic Dermatitis (AD), Autoimmune Hemolytic Anemia, Berylliosis, Bullous dermatitis herpetiformis, Chapped skin, Chronic Eczema, Chronic Inflammatory Skin Diseases, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Crohn's Disease (CD), Dental Cavity, Dermatitis, Dermatitis, Contact, Dermatitis, Eczematous, Dermatomyositis, Diaper Rash, Discoid Lupus Erythematosus (DLE), Edema of the cerebrum, Epicondylitis, Erythroderma, Fungal infectious disorders of the Beard, Gingivitis, Hemangiomas, Hemorrhoids, Hypercalcemia, Infected Wound, Infections, Fungal, Inflammation of Mouth, Intertrigo, Itching of the Anus, Itching of the External Genitalia, Itching of the Foot, Itching of the genitals, Itching of the hand, Juvenile Idiopathic Arthritis (JIA), Keloid Scars, Leukemias, Lichen Planus (LP), Lichen simplex chronicus, Malignant Lymphomas, Mycosis Fungoides (MF), Mycotic Eczema, Necrobiosis lipoidica diabeticorum, Neurodermatitis, Nummular Dermatitis, Ocular Inflammation, Ophthalmia, Sympathetic, Oral Erosive Lichen Planus, Oral Infection, Otitis Externa, Pemphigus, Pericarditis, Polymyositis, Post-Herpetic Neuralgia (PHN), Primary adrenocortical insufficiency, Proteinuria, Psoriasis Vulgaris (Plaque Psoriasis), Psoriatic Arthritis, Psoriatic plaque, Pure Red Cell Aplasia, Purulent Wounds, Pyoderma caused by susceptible bacteria, Regional Enteritis, Rheumatoid Arthritis, Ringworm Folliculitis, Seborrheic Dermatitis, Seborrheic Dermatitis, Eczematous, Secondary Impetiginization, Secondary adrenocortical insufficiency, Secondary thrombocytopenia, Serum Sickness, Skin Mycoses, Stomatitis, Aphthous, Stomatitis, Denture, Synovitis, Systemic Lupus Erythematosus (SLE), Temporal Arteritis, Tinea Corporis, Transfusion Reactions, Trichinosis, Tuberculosis (TB), Ulcerative Colitis, Urticaria, Uveitis, Acute Bursitis, Acute Multiple sclerosis, Acute Rheumatic heart disease, unspecified, Acute Tenosynovitis, Corticosteroid-responsive dermatoses, Cutaneous candidiasis, Cystic tumour of the ganglia, Exfoliative erythroderma, Granuloma annulare lesions, Idiopathic eosinophilic pneumonias, Non-suppurative Thyroiditis, Oral infections, Oral lesions, Severe Erythema multiforme, Subacute Dermatitis, Eczematous, Symptomatic Sarcoidosis, Ulceration of the mouth, Ulcerative stomatitis

How Econophen G works

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane.[A233320] Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. 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.[A232324, A232329] Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, 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.[A232329, A232339] Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation.[A232344] Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.

Corticosteroids like triamcinolone inhibit phospholipase A2 on cell membranes, preventing the breakdown of lysosomal membranes of leukocytes, which in turn prevent the formation of arachidonic acid, which decrease expression of cyclooxygenase and lipoxygenase, inhibiting synthesis of prostaglandins and leukotrienes. Anti-inflammatory activity occurs via reversal of vascular dilation and reducing permeability, which prevents macrophage and leukocyte migration. Triamcinolone also inhibits nuclear factor kappa-B, which decreases the production of pro-inflammatory signals such as interleukin-6, interleukin-8, and monocyte chemoattractant protein-1.

Dosage

Econophen G dosage

Eye: 1-2 drops instilled in affected eye up to 6 times a day or more frequently if required (severe infections may require 1-2 drops every 15-20 minutes initially, reducing the frequency of instillation gradually as the infection is controlled).

Ear: The area should be cleaned and 2-3 drops should be instilled every 3-4 times a day and at night, or more frequently if required.

A small amount of Gentamicin should be applied gently to the affected areas three to four times daily. The area treated may be covered with a gauze dressing if desired. Before applying the medication the affected area should be properly cleaned.

A small amount of Triamcinolone is gently rub to the affected area 1-2 times daily. Some cases of eczematised psoriasis may be treated more effectively by the application of Triamcinolone under an occlusive dressing.

Occlusive dressing technique: Gently rub a small amount of Triamcinolone on the lesion until it disappears. Then reapply, leaving a thin coating and cover with a pliable non porous film. For convenience apply Triamcinolone intermittently (12 hour occlusion during the night) followed by reapplication without occlusion, during the day.

Pediatric use: Triamcinoloneshould not be used in children under 8 years. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children. As children are more likely to get side effects, they should not normally be treated for longer than 5 days.

Side Effects

In patients with dermatoses treated with gentamicin, irritation (erythema and pruritus) had been reported in small number of cases. Itching, redness, swelling or other signs of irritation may develop. With the eye/ear drop bacterial and corneal ulcer have developed during treatment with gentamicin. Most frequently reported adverse reactions are ocular burning and irritation upon drug instillation, non specific conjunctivitis, conjunctival epithelial defects, and conjunctival hyperemia.

Gentamicin cream is well tolerated. There has been no evidence of irritation and sensitization after using Gentamicin cream.

The following local side effects have been reported with topical corticosteroids, either with or without occlusive dressings: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis and allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria.

Toxicity

As with other aminoglycosides, nephrotoxicity and ototoxicity are associated with gentamicin. Signs of nephrotoxicity include an increase in plasma creatinine and urea, while signs of ototoxicity include issues with balance, nausea, tinnitus, and hearing loss. It is important to note that aminoglycoside-induced nephrotoxicity is typically reversible, while ototoxicity is more likely to be permanent. The risk of both toxicities increases with long-term gentamicin therapy. Gentamicin is considered to be more vestibulotoxic than cochleotoxic compared to other aminoglycosides. Unfortunately, gentamicin-related ototoxicity does not correlate with cumulative dosing, peak and trough levels, or dosing schedule. The unpredictability of ototoxicity supports close monitoring of the patient throughout treatment. In cases of toxicity or overdose, the medication should be discontinued immediately; hemodialysis may be initiated to lower gentamicin serum concentrations.

The subcutaneous LD₅₀ of triamcinolone acetonide in rats is 13,100µg/kg and in mice is 132mg/kg. The oral LD₅₀ in rats is 1451mg/kg and in mice is 2168mg/kg.[LD₅₀] The intraperitoneal LD₅₀ in mice is 105mg/kg.[LD₅₀]

Patients experiencing an overdose may develop Cushing's syndrome. This overdose may be treated with supportive therapy and mifepristone for its antiglucocorticoid activity.

Precaution

If these occurs or if irritation, sensitization develops, treatment with gentamicin should be discontinued and appropriate therapy instituted. Gentamicin ear/eye drops is not for injection. It should never be injected subconjunctivally, nor it should be directly introduced into the anterior chamber of the eye.

Use of topical antibiotics occasionally cause overgrowth of nonsusceptible organisms including fungi. If this occurs or if irritation, sensitisation or super infection develops, treatment with Gentamicin should be discontinued and appropriate therapy should be instituted.

If reactions or idiosyncrasies are encountered, Triamcinolone Acetonide should be discontinued. The use of topical steroids on infected areas should be attended with caution and careful observation, bearing in mind the potential spreading of infections by anti-inflammatory steroids and the possible advisability of discontinuing steroid therapy and/or initiating antibacterial measures.

Triamcinolone Acetonide should not be used on healthy skin or over large areas of skin and not to be used in the eye as there is potential risk of glaucoma and cataract. When steroids are applied for long periods of time (more than 4 weeks) the occurrence of atrophic striae is likely. Prolonged use on flexures and intertriginous areas is undesirable. Children may absorb proportionately larger amounts of topical corticosteroids and thus may be more susceptible to systemic toxicity. In infants, long term continuous topical steroid therapy should be avoided. Adrenal suppression can occur even without occlusion.

Interaction

None has been reported so far with topical and Eye/Ear drops.

Volume of Distribution

The apparent volume of distribution of triamcinolone is 115.2±10L. The mean apparent volume of distribution of triamcinolone acetonide is 1.96L/kg. The apparent volume of distribution of triamcinolone diacetate is 119.7±33.14L.

Elimination Route

A 16mg oral dose of triamcinolone reaches a C_max of 5.23±0.84ng/mL with a T_max of 2.24±0.78h and an AUC of 36.0±6.2ng*h/mL.

A 2mg intravenous dose of triamcinolone acetonide has an AUC of 57.7ng*h/mL. The bioavailability of 800µg of inhaled triamcinolone acetonide is 25%, with 10.4% coming from pulmonary absorption and the rest being accounted for by deposition on the oral mucosa and other underlying factors. An inhaled dose of triamcinolone acetonide reaches a C_max of 0.92ng/mL with a T_max of 1.74h and an AUC of 5.12ng*h/mL. The fraction of an inhaled dose that is actually absorbed via the pulmonary route reaches a C_max of 0.55ng/mL with a T_max of 0.66h and an AUC of 2.15ng*h/mL.

A 16mg oral dose of triamcinolone diacetate reaches a C_max of 5.33±1.55ng/mL with a T_max of 1.86±0.47h and an AUC of 32.7±9.9ng*h/mL.

Half Life

One study assessing the pharmacokinetics of gentamicin in children and adults reported a mean half-life of 75 minutes after intravenous administration. The mean half-life associated with intramuscular administration was about 29 minutes longer. Fever and anemia may result in a shorter half-life although dose adjustments are not usually necessary. Severe burns are also associated with a shorter half-life and may result in lower gentamicin serum concentrations.

The half life of triamcinolone is 2.7h. The mean terminal elimination half life following an inhaled dose of triamcinolone acetonide is 2.4h. The half life of triamcinolone diacetate is 2.8h.

Clearance

The renal clearance of gentamicin is comparable to individual creatinine clearance.

The clearance of triamcinolone is 28.6±5.6L/h. The mean total body clearance of triamcinolone acetonide is 0.57L/h. The clearance of triamcinolone diacetate is 34.4±10.6L/h.

Elimination Route

Gentamicin is excreted primarily by the kidneys. In patients with normal renal function, 70% or more of an initial gentamicin dose can be recovered in the urine within 24 hours. Excretion of gentamicin is significantly reduced in patients with renal impairment.

Approximately 20% of a dose of triamcinolone is recovered in the urine as the unchanged drug, 25% is recovered as 6-beta-hydroxy-triamcinolone, and 5% is recovered as unidentified metabolites.

Pregnancy & Breastfeeding use

Consideration should be given the possibility of foetal ototoxicity when gentamicin is applied topically to large denuded areas of skin. For Gentamicin Eye/Ear Drops safety profile in pregnancy is not yet established and should be administered when considered essential.

There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether topical administration of corticosteroid could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman.

Contraindication

Gentamicin is contraindicated in individuals with a history of sensitivity reaction to any of its components. Use of topical Gentamicin may occasionally allow overgrowth of nonsusceptible organisms, including fungi.

Triamcinolone Acetonide is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation. It is also contraindicated in tuberculosis of the skin, fungus infections and viral diseases of the skin (Herpes simplex, chickenpox and vaccinia), perioral dermatitis, rosacea and ulcerative conditions.

Acute Overdose

Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects e.g., mild, reversible suppression of adrenal function, ecchymoses of the skin, peptic ulceration, hypertension, aggravation of infection, hirsutism, acne, edema and muscle weakness

Storage Condition

To avoid contamination, do not touch the tip of the container to the eye, eyelid or any surface.

Store in a cool & dry place. Protect from light.

Innovators Monograph

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