Erysil

Uses

Erythromycin tablet is highly effective in the treatment of a wide variety of clinical infections, such as

• Upper respiratory tract infections: Tonsillitis, peritonsillar abscess, pharyngitis, laryngitis, sinusitis, and secondary infections in cold and influenza.
• Lower respiratory tract infections: Tracheitis, acute and chronic bronchitis. Mycoplasma pneumoniae (lobar pneumonia, broncho pneumonia, primary atypical pneumoniae), bronchiectasis.
• Skin and soft tissue infections: Boils and carbuncles, paronychia, abscesses, pustular acne, impetigo, cellulitis, furuncolosis, erythrasma.
• Veneral infections: Non-specific urethritis, syphilis (if the patient is allergic to penicillin).
• Gastro-intestinal infections: Cholecystitis, Staphylococcal enterocolitis, infectious diarrhoea, & cholera.
• Ear and oral infections: 0titis media and otitis externa, gingivitis, dental abscesses.
• Prophylaxis: Pre-operative and post-operative, trauma, burns, rheumatic fever.
• Other infections: Diphtheria, whooping cough.

For topical treatment of acne, pimples & bacterial skin infections susceptible to Erythromycin

Zinc is an essential element commonly used for the treatment of patients with documented zinc deficiency.

Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections .

Erysil is also used to associated treatment for these conditions: Acne, Acne Vulgaris, Acute Otitis Media caused by Haemophilus Influenzae, Acute pelvic inflammatory disease caused by Neisseria Gonorrheae Infection, Bacterial Infections, Chancroid, Chlamydia Trachomatis, Chlamydial ophthalmia neonatorum, Community Acquired Pneumonia (CAP), Diphtheria, Erythrasma, Gastroparesis, Granuloma Inguinale, Intestinal amebiasis caused by entamoeba histolytica, Legionella Pneumophila Infections, Listeria infection, Lower Respiratory Tract Infection (LRTI), Lymphogranuloma Venereum, Nongonococcal urethritis, Ophthalmia neonatorum (gonococcal), Pertussis, Postoperative Infections, Primary Syphilis, Respiratory Tract Infections (RTI), Staphylococcal Skin Infections, Syphilis, Upper Respiratory Tract Infection, Ureaplasma urethritis, Whooping Cough, Inflammatory papular lesions, Mild Acne vulgaris, Moderate Acne vulgaris, Predominant skin comedones, papules and pustules, Prophylaxis of Rheumatic fever, Pustular lesions, Skin and skin-structure infections, Skin and subcutaneous tissue bacterial infections caused by streptococcus pyogenes, Superficial ocular infectionsCandidiasis, Common Cold, Diaper Dermatitis, Diaper Rash, Eye redness, Iron Deficiency (ID), Ocular Irritation, Skin Irritation, Sunburn, Wilson's Disease, Zinc Deficiency, Dietary and Nutritional Therapies, Dietary supplementation

How Erysil works

In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Erythromycin acts by inhibition of protein synthesis by binding to the 23S ribosomal RNA molecule in the 50S subunit of ribosomes in susceptible bacterial organisms. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit. This results in the control of various bacterial infections. The strong affinity of macrolides, including erythromycin, for bacterial ribosomes, supports their broad‐spectrum antibacterial activities.

Zinc has three primary biological roles: catalytic, structural, and regulatory. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately 3000 human proteins including enzymes, nuclear factors, and hormones .

Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins .

In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8 .

There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine 3-5-cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to 30 September 2016 .

Zinc deficiency in humans decreases the activity of serum thymulin (a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans [A342417].

The change of Th(1) to Th(2) function leads to cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells [A3424].

In humans, zinc deficiency may lead to the generation of new CD4+ T cells, produced in the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production .

In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers [A3424]. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In such cells, zinc was found to induce A20, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers .

The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels .

Dosage

Erysil dosage

Adult and Child over 8 years: 250-500 mg every 6 hours or 0.5-1 gm every 12 hours. This may be increased up to 4 gm daily according to severity of infections.

Child of 2-8 years: 250 mg every 6 hours, doses doubled for severe infections.

Child up to 2 years: 125 mg every 6 hours.

Neonates: 30 to 45 mg/kg daily in 3 divided doses.

Elderly: Same as for adults.If administration on a twice daily schedule is desirable, one half of the total daily dose may be given every 12 hours, one hour before meal.

Amoebic dysentery:

• Adult: 250 - 500 mg four times daily for 10 - 14 days.
• Children: 30 - 50 mg/kg/day in divided doses for 10 - 14 days.

Pertussis: 30 - 50 mg/kg/day in divided doses for 5-14 days depending upon eradication of a positive culture.Streptococcal infections: In the treatment of group A beta haemolytic streptococcal infections, therapeutic dosage of Erythromycin should be administered for at least 10 days.

Acne: The usual dosage regimen of erythromycin in the treatment of acne is 500 mg twice daily for 3 months. Then the dose is to be reduced to 250 mg twice daily for another 3 months.

Early Syphilis: 500 mg 4 times daily for 14 days.Uncomplicated genital Chlamydia nongonococcal Urethritis: 500 mg twice daily for 14 days.

Prophylaxis: In continuous prophylaxis of streptococcal infections in person with a rheumatic heart disease, the dosage is 250 mg twice daily.

When Erythromycin is used prior to surgery to prevent endocarditis caused by alpha haemolytic streptococci, a recommended schedule:

• For children: 20 mg/Kg 1.5 - 2 hours pre-operatively and 10 mg/kg every 6 hours for 8 doses post-operatively.
• For adults:The dose is 1 g, 1.5 - 2 hours pre-operatively and 500 mg every 6 hours for 8 doses post-operatively.

Topical: Apply to the affected areas in the morning and evening. Before applying thoroughly wash with warm water and soap, rinse and pat dry all areas to be treated. Apply with applicator. Wash hands after use.

Direction for reconstitution of suspension: Shake the bottle to loosen powder. Add 60 ml (12 measuring spoonful) of boiled and cooled water to the dry powder of the bottle. For ease of preparation, add water to the bottle in two proportions. Shake well after each addition until all the powder is in suspension.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place, preferably in refrigerator and unused portion should be discarded after 7 days.

Side Effects

Generally erythromycin is well tolerated and serious adverse effects are rare. Side-effects are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Mild allergic reactions, such as urticaria and skin rashes have occurred. Serious allergic reactions, including anaphylaxis may occur.

Toxicity

LD50

The oral LD50 of erythromycin in rats is 9272 mg/kg.

Overdose information

Symptoms of overdose may include diarrhea, nausea, stomach cramps, and vomiting. Erythromycin should immediately be discontinued in cases of overdose. Rapid elimination of unabsorbed drug should be attempted. Supportive measures should be initiated. Erythromycin is not adequately removed by peritoneal dialysis or hemodialysis.

According to the Toxnet database of the U.S. National Library of Medicine, the oral LD50 for zinc is close to 3 g/kg body weight, more than 10-fold higher than cadmium and 50-fold higher than mercury .

The LD50 values of several zinc compounds (ranging from 186 to 623 mg zinc/kg/day) have been measured in rats and mice .

Precaution

Lotion/Cream: For external use only. Keep away from eyes, nose, mouth and other mucous membrane.

Use of antibiotics (especially prolonged or repeated therapy) may result in bacterial or fungal overgrowth of non-susceptible organisms. Such overgrowth may lead to a secondary infection. Take appropriate measures if superinfections occur.

Tablet: Since Erythromycin is metabolized principally by the liver, caution should be exercised when erythromycin is administered to patients with impaired hepatic function. There have been reports of hepatic dysfunction with or without jaundice occurring in patients taking oral Erythromycin.

Interaction

Theophylline: The use of Erythromycin in patients who are receiving concomitant high doses of theophylline may be associated with an increase in serum theophylline and potential theophylline toxicity. If symptoms of toxicity develop, the dose of theophylline should be reduced.

Digoxin: Concomitant administration of Erythromycin and Digoxin has been reported to result in elevated digoxin serum levels.

Clindamycin interacts with Erythromycin

Volume of Distribution

Erythromycin is found in most body fluids and accumulates in leucocytes and inflammatory liquid. Spinal fluid concentrations of erythromycin are low, however, the diffusion of erythromycin through the blood-brain barrier increases in meningitis, likely due to the presence of inflamed tissues which are easily penetrated. Erythromycin crosses the placenta.

A pharmacokinetic study was done in rats to determine the distribution and other metabolic indexes of zinc in two particle sizes. It was found that zinc particles were mainly distributed to organs including the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender .

Elimination Route

Orally administered erythromycin is readily absorbed. Food intake does not appear to exert effects on serum concentrations of erythromycin. Some interindividual variation exists in terms of erythromycin absorption, which may impact absorption to varying degrees. The Cmax of erythromycin is 1.8 mcg/L and the Tmax is 1.2 hours. The serum AUC of erythromycin after the administration of a 500mg oral dose was 7.3±3.9 mg.h/l in one pharmacokinetic study. Erythromycin is well known for a bioavailability that is variable (18-45%) after oral administration and its susceptibility to broken down under acidic conditions.

Zinc is absorbed in the small intestine by a carrier-mediated mechanism . Under regular physiologic conditions, transport processes of uptake do not saturate. The exact amount of zinc absorbed is difficult to determine because zinc is secreted into the gut. Zinc administered in aqueous solutions to fasting subjects is absorbed quite efficiently (at a rate of 60-70%), however, absorption from solid diets is less efficient and varies greatly, dependent on zinc content and diet composition .

Generally, 33% is considered to be the average zinc absorption in humans . More recent studies have determined different absorption rates for various populations based on their type of diet and phytate to zinc molar ratio. Zinc absorption is concentration dependent and increases linearly with dietary zinc up to a maximum rate [L20902].

Additionally zinc status may influence zinc absorption. Zinc-deprived humans absorb this element with increased efficiency, whereas humans on a high-zinc diet show a reduced efficiency of absorption .

Half Life

The elimination half-life of oral erythromycin was 3.5 hours according to one study and ranged between 2.4-3.1 hours in another study. Repetitive dosing of erythromycin leads to increased elimination half-life.

The half-life of zinc in humans is approximately 280 days .

Clearance

The clearance of erythromycin in healthy subjects was 0.53 ± 0.13 l/h/kg after a 125mg intravenous dose. In a clinical study of healthy patients and patients with liver cirrhosis, clearance of erythromycin was significantly reduced in those with severe liver cirrhosis. The clearance in cirrhotic patients was 42.2 ± 10.1 l h–1 versus 113.2 ± 44.2 l h-1 in healthy patients.

In one study of healthy patients, the clearance of zinc was found to be 0.63 ± 0.39 μg/min .

Elimination Route

In patients with normal liver function, erythromycin concentrates in the liver and is then excreted in the bile.Under 5% of the orally administered dose of erythromycin is found excreted in the urine. A high percentage of absorbed erythromycin is not accounted for, but is likely metabolized.

The excretion of zinc through gastrointestinal tract accounts for approximately one-half of all zinc eliminated from the body .

Considerable amounts of zinc are secreted through both biliary and intestinal secretions, however most is reabsorbed. This is an important process in the regulation of zinc balance. Other routes of zinc excretion include both urine and surface losses (sloughed skin, hair, sweat) .

Zinc has been shown to induce intestinal metallothionein, which combines zinc and copper in the intestine and prevents their serosal surface transfer. Intestinal cells are sloughed with approximately a 6-day turnover, and the metallothionein-bound copper and zinc are lost in the stool and are thus not absorbed .

Measurements in humans of endogenous intestinal zinc have primarily been made as fecal excretion; this suggests that the amounts excreted are responsive to zinc intake, absorbed zinc and physiologic need .

In one study, elimination kinetics in rats showed that a small amount of ZnO nanoparticles was excreted via the urine, however, most of the nanoparticles were excreted via the feces .

Pregnancy & Breastfeeding use

Safety for use during pregnancy has not been established. Use only when the potential benefits outweigh potential hazards to the fetus.

Erythromycin is excreted in breast milk. Exercise caution when administering to a nursing mother.

Contraindication

Erythomycin is contraindicated in patients with a known hypersensitivity to this drug.

Special Warning

Safety and effectiveness in children less than 12 years have not been established.

Acute Overdose

In case of overdosage, Erythromycin should be discontinued. Overdosage should be handled with the prompt elimination of unabsorbed drug and all other appropriate measures should be instituted. Erythromycin is not removed by peritoneal dialysis or haemodialysis.

Storage Condition

Keep at room temperature and away from light.

Innovators Monograph

You find simplified version here Erysil