Pred 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.

Prednisolone eye drops is used for the treatment of steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.

Prednisolone tablet, Injection is used forAllergy and anaphylaxis: bronchial asthma, drug hypersensitivity reactions, serum sickness, angioneurotic oedema, anaphylaxis.

Respiratory disease: allergic pneumonitis, asthma, occupational asthma, pulmonary aspergillosis, pulmonary fibrosis, pulmonary alveolitis, aspiration of foreign body, aspiration of stomach contents, pulmonary sarcoid, drug induced lung disease, adult respiratory distress syndrome, spasmodic croup.

Rheumatic disorders: rheumatoid arthritis, polymyalgia rheumatica, juvenile chronic arthritis, systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease.

Arteritis/collagenosis: giant cell arteritis/polymyalgia rheumatica, mixed connective tissue disease, polyarteritis nodosa, polymyositis.

Blood disorders: haemolytic anaemia (auto-immune), leukaemia (acute and chronic lymphocytic), lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura.

Cardiovascular disorders: post-myocardial infarction syndrome, rheumatic fever with severe carditis.

Endocrine disorders: primary and secondary adrenal insufficiency, congenital adrenal hyperplasia.

Gastro-intestinal disorders: Crohn's disease, ulcerative colitis, persistent coeliac syndrome (coeliac disease unresponsive to gluten withdrawal), auto-immune chronic active hepatitis, multisystem disease affecting liver, biliary peritonitis.

Infections (with appropriate chemotherapy): helminthic infestations, Herxheimer reaction, infectious mononucleosis, miliary tuberculosis, mumps orchitis (adult), tuberculous meningitis, rickettsial disease.

Muscular disorders: polymyositis, dermatomyositis.

Neurological disorders: infantile spasms, Shy-Drager syndrome, sub-acute demyelinating polyneuropathy.

Ocular disease: scleritis, posterior uveitis, retinal vasculitis, pseudo-tumours of the orbit, giant cell arteritis, malignant ophthalmic Graves disease.

Renal disorders: lupus nephritis, acute interstitial nephritis, minimal change glomerulonephritis.

Skin disorders: pemphigus vulgaris, bullous pemphigoid, systemic lupus erythematosus, pyoderma gangrenosum.

Miscellaneous: sarcoidosis, hyperpyrexia, Behçets disease, immunosuppression in organ transplantation.

Prednisolone is used for the treatment of steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.

Pred 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 infectionInflammation, Inflammatory Conditions, Ocular Infections, Irritations and Inflammations, Ocular Inflammation, Organ Transplant Rejection

How Pred 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.

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

Dosage

Pred 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.

The initial dosage of Prednisolone may vary from 5 mg to 60 mg daily depending on the disorder being treated. Divided daily dosage is usually used.

The appropriate individual dose must be determined by trial and error and must be re-evaluated regularly according to activity of the disease.

In general, initial dosage shall be maintained or adjusted until the anticipated response is observed. The dose should be gradually reduced until the lowest dose, which will maintain an adequate clinical response is reached.

During prolonged therapy, dosage may need to be temporarily increased during periods of stress or during exacerbations of the disease. When the drug is to be stopped, it must be withdrawn gradually and not abruptly.

Intermittent dosage regimen: A single dose of Prednisolone in the morning on alternate days or at longer intervals is acceptable therapy for some patients. When this regimen is practical, the degree of pituitary-adrenal suppression can be minimized.

Use in children: Corticosteroids cause growth retardation in infancy, childhood and adolescence, which may be irreversible. Treatment should be administered where possible as a single dose on alternate days.

Specific dosage guidelines-

Allergic and skin disorders: initial doses of 5-15 mg daily are commonly adequate.

Collagenosis: Initial doses of 20-30 mg daily are frequently effective. Those with more severe symptoms may require higher doses.

Rheumatoid arthritis: The usual initial dose is 10-15 mg daily. The lowest daily maintenance dose compatible with tolerable symptomatic relief is recommended.

Blood disorders and lymphoma: An initial daily dose of 15-60 mg is often necessary with reduction after an adequate clinical or haematological response. Higher doses may be necessary to induce remission in acute leukaemia.

Adult: Instill one drop into the conjunctival sac two to four times daily. During the initial 24 to 48 hours, the dosing frequency may be increased if necessary. Care should be taken not to discontinue the therapy before completing the course.

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

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.

Elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation and delayed wound healing. Fungal and viral infections of the cornea are particularly may develop coincidentally with long-term applications of steroid.

General side-effects include leucocytosis, hypersensitivity including anaphylaxis, thromboembolism, nausea, and malaise.

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 oral LD₅₀ of prednisolone acetate in mice is 1680 mg/kg. Patients experiencing an overdose of oral prednisolone acetate may experience an increased severity in the adverse effects of corticosteroids. Overdose of oral prednisolone acetate may be treated by gastric lavage or inducing vomiting if the overdose was recent, as well as supportive and symptomatic therapy. Chronic overdosage may be treated by dose reduction or treating patients on alternate days. An overdose by the ophthalmic route is not expected to cause problems.

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.

Shake the bottle well before use. Prolonged use of corticosteroids may result in damage to the optic nerve and defects in vision. If this product is used for longer period of time, intraocular pressure should be routinely monitored.

Caution is necessary when oral corticosteroids, including Prednisolone, are prescribed in patients with the following conditions like-Tuberculosis, Hypertension, Congestive heart failure, Liver failure, Renal insufficiency, Diabetes mellitus or in those with a family history of diabetes, Osteoporosis, Patients with a history of severe affective disorders and particularly those with a previous history of steroid-induced psychoses, Epilepsy, Peptic ulceration, Previous Steroid Myopathy.

Undesirable effects may be minimized by using the lowest effective dose for the minimum period and by administering the daily requirement as a single morning dose on alternate days. Frequent patient review is required to titrate the dose appropriately against disease activity.

Interaction

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

Hepatic microsomal enzyme inducers: Drugs which can cause liver enzyme induction such as phenobarbitone, phenytoin, rifampicin, rifabutin, carbamazepine, primidone and aminoglutethimide may reduce the therapeutic efficacy of corticosteroids by increasing the rate of metabolism.

Non-steroidal anti-inflammatory drugs: Concomitant administration of ulcerogenic drugs such as indomethacin during corticosteroid therapy may increase the risk of Gl ulceration.

Anticoagulants: Response to anticoagulants may be reduced or, less often, enhanced by corticosteroids.

Vaccines: Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.

Oestrogens: Oestrogens may potentiate the effects of glucocorticoids and dosage adjustment may be required if oestrogens are added to or withdrawn from a stable dosage regimen.

Other: The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids and the hypokalaemic effect of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced.

Volume of Distribution

The volume of distribution of the active metabolite, prednisolone, is 0.22/0.7L/kg.

Elimination Route

Prednisolone acetate oral suspension given at a dose equivalent to 15mg prednisolone has a C_max of 321.1ng/hr, a T_maxof 1-2 hours, and an AUC of 1999.4ng*hr/mL. The absorption pharmacokinetics of prednisolone acetate are not significantly different from a comparable dose of prednisolone.

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.

Oral prednisolone acetate has a plasma half life of 2-3 hours.

Clearance

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

Data regarding the clearance of prednisolone acetate is not readily available.

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.

Prednisolone acetate is predominantly excreted in the urine.

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.

Pregnancy: Prednisolone Acetate is pregnancy category C. So, this drug should be used during pregnancy only if clearly needed.

Lactation: Corticosteroids are excreted in small amounts in breast milk and infants of mothers taking pharmacological doses of steroids should be monitored carefully for signs of adrenal suppression.

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.

Prednisolone (Eye drops) is contraindicated in viral diseases of the cornea, conjunctiva and known hypersensitivity to any of the ingredients of Prednisolone (Eye drops) or other corticosteroids.

Systemic infections unless specific anti-infective therapy is employed. Hypersensitivity to any ingredient. Ocular herpes simplex because of possible perforation.

Special Warning

Use in the elderly: Treatment of elderly patients, particularly if long term, should be planned bearing in mind the more serious consequences of the common side effects of corticosteroids in old age, especially osteoporosis, diabetes, hypertension, hypokalemia, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

May need to increase dose in patients with hyperthyroidism to achieve therapeutic effects.

Acute Overdose

A one-time accidental overdose of Prednisolone Ophthalmic Suspension generally will not cause acute problems. Long time overdose may show general side-effects. In accidental overdose sufficient water should be taken to dilute the medication.

Report of acute toxicity and/or death following overdose of glucocorticoids are rare. No specific antidote is available; treatment is supportive and symptomatic. Serum electrolytes should be monitored.

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 and protect from light. Keep out of the reach of children. Protect from freezing. Shake well before using.

Innovators Monograph

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