Silvonir

Uses

For antisepsis of clean and surgical hand to prevent infections

Metronidazole is used for:

• All forms of amoebiasis (intestinal and extra-intestinal disease including liver abscess and that of symptomless cyst passers)
• Trichomoniasis
• Giardiasis
• Bacterial vaginosis
• Acute ulcerative gingivitis
• Anaerobic infections including septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis etc.
• Anaerobically-infected leg ulcers and pressure sores
• Acute dental infections (e.g. acute pericoronitis and acute apical infections)
• Surgical prophylaxis (prevention of postoperative infections due to anaerobic bacteria, particularly species of bacteroides and anaerobic streptococci
• Chronic symptomatic peptic ulcer disease (as an agent of triple therapy to eradicate H. pylori-the most important aetiological factor of peptic ulcer)

Prophylaxis and treatment of infection in burn wounds-

As an adjunct to short-term treatment of infection in

• Leg ulcers
• Pressure sores

As an adjunct to prophylaxis of infection in

• Skin graft donor sites
• Extensive abrasions

Conservative management of Finger-tip injuries

Silver Sulphadiazine is a local chemotherapeutic agent for prevention and treatment of burn wound infections. Silver Sulphadiazine disintegrates in the burn wound, thereby causing a slow and sustained release of silver ions. Silver ions bind to bacterial Deoxyribonucleic acid (DNA), thus inhibiting the growth and multiplication of bacterial cells without affecting the cells of the skin and subcutaneous tissue. Silver Sulfadiazine cream has a broad antibacterial spectrum including virtually all microbial species likely to infect the burn wound: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, strains of Proteus and Klebsiella. It is also an effective agent against Candida albicans and other fungi. Silver Sulfadiazine penetrates into the necrotic tissue and exudate. This effect is very important in view of the fact that systemic antibiotics are not effective against the bacterial flora of vascular burn necrosis.

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 .

Silvonir is also used to associated treatment for these conditions: Catarrh of the throat, Chemotherapy Induced Mucositis, Chronic Wounds, Decubitus Ulcer, Dental Cavity, Dysphagia, Eczema infected, Foeter Ex Ore, Gingival Bleeding, Gingival disorders NEC, Gingivitis, Glossitis, Hoarseness, Infection, Infectious Periodontal Diseases, Injury Throat, Mild to Moderate Inflammatory Reaction of the Oral Cavity, Mild to Moderate Inflammatory Reaction of the Pharynx, Mouth injury, Mucositis, Neurodermatitis, Ocular Inflammation, Ocular Irritation, Oral Aphthous Ulcer, Oral Infection, Pain, Periodontitis, Pharyngitis, Plaque, Dental, Postoperative Wound Infection, Purulent Gingivitis, Radiation Mucositis, Red eye, Ringworm, Skin Infections, Skin Infections, Bacterial, Sore Throat, Stomatitis, Surgical Wound, Tissue Damage, Tonsillitis, Ulcer, Aphthous, Ulcers, Leg, Wound Infections, Dry, cracked skin, Gum disorder, Gum pain, Moderate Gingivitis, Oral lesions, Recurrent Oral fungal infection, Severe Gingivitis, Superficial Wounds, Throat disinfection, Tongue inflammation, Anesthesia of Mucous Membrane, Antimicrobial Therapy, Contact Lens Care, Disinfection, Disinfection of External Genitalia, Disinfection of the Urethra, Disinfection of the Vaginal Mucosa, Irrigation therapy, Lubrication of the Urethra, Oral Care, Oral Hygiene, Oropharyngeal antisepsis, Skin disinfection, Surgical Scrubbing, Topical Antisepsis, Urethral Anesthesia, Wound Cleansing, Wound Healing, Oral antisepsis, Oral disinfectionAbscess, Intra-Abdominal, Acne Rosacea, Amebiasis, Anaerobic Infection, Bacteremia, Bacterial Endocarditis, Bacterial Peritonitis, Bacterial Vaginosis (BV), Balantidiasis, Bloodstream Infections, Bone and Joint Infections, Brain abscess, CNS Infection, Candidal Vulvovaginitis, Clostridium Difficile Infection (CDI), Empyema, Endometritis, Endomyometritis, Facial Rosacea, Giardiasis, Gynaecological infection, Helicobacter Pylori Infection, Infection, Bacteroides, Intraabdominal Infections, Lower Respiratory Infection, Lower respiratory tract infection bacterial, Lung Abscess, Meningitis, Mixed Vaginal Infections, Parasitic infection NOS, Periodontitis, Pneumonia, Postoperative Infections, Pouchitis, Septicemia bacterial anaerobic, Skin and Subcutaneous Tissue Bacterial Infections, Tetanus, Trichomonal Vaginitis, Trichomonas Vaginitis, Tubo-ovarian abscess, Urethritis, Vulvovaginitis, Asymptomatic Trichomoniasis, Entamoeba histolytica, Hepatic abscess, Refractory Sinusitis, Skin and skin-structure infections, Symptomatic Trichomoniasis, Asymptomatic InfectionsWound 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 Silvonir works

Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death. The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.

The exact mechanism of action of metronidazole has not been fully established, however, it is possible that an intermediate in the reduction of metronidazole which is only made by anaerobic bacteria and protozoa, binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis. After administration, metronidazole enters cells by passive diffusion. Following this, ferredoxin or flavodoxin reduce its nitro group to nitro radicals. The redox potential of the electron transport portions of anaerobic or microaerophilic microorganisms renders metronidazole selective to these organisms, which cause nitro group reduction, leading to the production of toxic metabolites. These include N-(2-hydroxyethyl) oxamic acid and acetamide, which may damage DNA of replicating organisms.

Studies utilizing radioactive micronized silver sulfadiazine, electron microscopy, and biochemical techniques have revealed that the mechanism of action of silver sulfadiazine on bacteria differs from silver nitrate and sodium sulfadiazine. Silver sulfadiazine acts only on the cell membrane and cell wall to produce its bactericidal effect. A specific mechanism of action has not been determined, but silver sulfadiazine's effectiveness may possibly be from a synergistic interaction, or the action of each component. Silver is a biocide, which binds to a broad range of targets. Silver ions bind to nucleophilic amino acids, as well as sulfhydryl, amino, imidazole, phosphate, and carboxyl groups in proteins, causing protein denaturation and enzyme inhibition. Silver binds to surface membranes and proteins, causing proton leaks in the membrane, leading to cell death. Sulfadiazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

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

Silvonir dosage

To sterilize clean hand: Take adequate amount (about 3 ml) of Sanityza on the palm of the both hands and wrists; rub until full drying as if every part is sterilized effectivelyBefore surgery: Apply about 5 ml of Sanityza following above mentioned method; apply upto the elbow

Tablet and Suspension:

Amoebic dysentery: Duration 5-10 Days;

• For Tablet: Adults- 750 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
• For Suspension: Adults- 800 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 200 mg q.i.d. (1-3 years) 200 mg t.i.d.

Asymptomatic amoebiasis: Duration 5-10 Days;

• For Tablet: Adults- 500-750 mg t.i.d. Children- (7-10 years) 250-500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
• For Suspension: Adults- 500-800 mg t.i.d. Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Hepatic extraintestinal amoebiasis : Duration 5-10 Days (or 2days);

• For Tablet: Adults- 500-750 mg t.i.d.; Children- (7-10 years) 250-500 mg t.i.d.; (3-7 years) 250 mg q.i.d.; (1-3 years) 250 mg t.i.d.
• For Suspension: Adults- 500-800 mg t.i.d.; Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Giardiasis: Duration 3 Days;

• For Tablet: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 750 mg once daily; (1-3 years) 500 mg once daily.
• For suspension: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 800 mg once daily; (1-3 years) 500 mg once daily.

Trichomoniasis: Duration 7 Days;

• For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Trichomoniasis: Duration 1 Day;

• For Tablet: Adults- 2 g single dose;
• For Suspension: Adults- 2 g single dose;

Vincent's infection (Ulceration of mucous membrane of respiratory tract & mouth): Duration 3 Days;

• For Tablet: Adults- 250 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 200 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Periodontal infection: Duration 3 Days;

• For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Severe dental infection: Duration 3 Days;

• For Tablet: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
• For Suspension: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Anaerobic infection: Duration 7 Days;

• For Tablet: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.
• For Suspension: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.

Postoperative anaerobic infection (specially in operation abdominal or gynecological surgery): Duration 7 Days;

• For Tablet: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.
• For Suspension: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.

Bacterial vaginitis: Duration 7 Days;

• For Tablet: Adults- 500 mg b.i.d.
• For Suspension: Adults- 500 mg b.i.d.

Leg ulcers: Duration 1 Day;

• For Tablet: Adults- 2 g as a single dose
• For Suspension: Adults- 2 g as a single dose

Pressure sores: Duration 7 Days;

• For Tablet: Adults- 500 mg t.i.d.
• For Suspension: Adults- 500 mg t.i.d.

H. pylori infection: Duration 7 Days;

• For Tablet: Adults- 500 mg b.i.d
• For Suspension: Adults-500 mg b.i.d

Antibiotic Associated Pseudomembranus colitis: Duration 7 Days;

• For Tablet: Adults- 500 mg b.i.d
• For Suspension: Adults- 500 mg b.i.d

Vaginal Gel:

The recommended dose is one applicator full of Metronidazole GEL (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole GEL should be administered at bedtime.

Suppository:

Anaerobic infections:

• Adult: 1 g 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
• Child: 5-10 yr 500 mg. All doses to be given 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

Prophylaxis of postoperative anaerobic bacterial infections:

• Adult: 1 g 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
• Child: 5-10 yr 500 mg 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

IV Infusion:

Metronidazole injection should be infused intravenously at an approximate rate of 5 ml/min. Oral medication should be substituted as soon as feasible. Treatment for 7 days should be satisfactory for most patients, but the physician might decide to prolong treatment.

• For bacterial infections: Adults: 500 mg (100 ml) 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly.
• For treatment before and during surgery: Adults: 500 mg (100 ml) shortly before operation, repeated 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly

Burns: Keep the burn wound in clean condition and apply Burnsil over the affected area to a depth of 3 to 5 mm. This application is best achieved with a sterile gloved hand and/or a sterile spatula. Where necessary, the cream should be re-applied to any area from which it has been removed by patient activity. In burns, Burnsil should be re-applied at least every 24 hours, or more frequently if the volume of exudate is large.

Hand burns: Apply Burnsil to the burn area and enclose with a clean plastic bag or glove upto wrist. The patient should be encouraged to move the hand and fingers. The dressing should be changed when an excessive amount of exudate has accumulated in the bag.

Leg ulcers/pressure sores: The cavity of ulcer should be filled with Burnsil to a depth of at least 3-5 mm. As Burnsil can cause maceration of normal skin on prolonged contact, care should be taken to prevent spread on the non-ulcerated areas. Application of Burnsil should be followed by an absorbed pad or gauze dressing, with further application of pressure bandaging as appropriate for the ulcer. The dressings should normally be changed daily but for wounds which are less exudative, less frequent changes (every 48 hours) may be acceptable. Cleanings and debriding should be performed before application of Burnsil. Burnsil is not recommended for use in leg or pressure ulcer that is very exudative.

Fingertip injuries: Haemostasis of the injury should be achieved prior to the application of a 3-5 mm layer of Burnsil . A conventional finger dressing may be used. Alternatively waterproof adhesive tape can be used on finger covered by a plastic or surgical glove. Dressings should be changed every 2-3 days.

Side Effects

Skin sensitivity; mucosal irritation; reversible brown staining of the teeth; tongue discoloration and burning sensation; transient taste disturbance; parotid gland swelling.

Side effects of Metronidazole include gastrointestinal discomfort, nausea, coated tongue, dryness of mouth and unpleasant metallic or bitter taste, headache, pruritus and skin rashes and less frequently, vertigo, depression, insomnia, drowsiness, urethral discomfort, and darkening of the urine. Occasionally there may be temporary moderate leucopenia. Peripheral neuropathy has been reported in patients on prolonged therapy.

In prolonged treatment of burn wounds involving extensive areas of the body the serum Sulphonamide concentrations may approach the levels equal to those in systemic treatment.

Toxicity

The LD₅₀ of subcutaneously administered chlorhexidine in mice is >5 g/kg.

Small children are likely to be more susceptible to chlorhexidine overdose - ingestion of 1-2 ounces by a small child may result in gastric distress, nausea, and intoxication. Treatment should consist of symptomatic and supportive measures. Seek medical attention if a child ingests >4 ounces of chlorhexidine solution or if symptoms of intoxication develop post-exposure.

LD50 information

The oral LD50 of metronidazole in rats is 5000 mg/kg

Overdose information

Adverse effects that may be exaggerated with an overdose include peripheral neuropathy, central nervous system toxicity, seizures, disulfiram-like effect (if combined with alcohol) dark urine, a metallic taste in the mouth, nausea, epigastric discomfort, and vertigo, in addition to neutropenia. There is no specific antidote for metronidazole overdose. Symptomatic and supportive treatment should be employed in addition to the administration of activated charcoal to remove the unabsorbed drug from the gastrointestinal tract. In addition to the above measures, contact the local poison control center for updated information on the management of a metronidazole overdose.

Acute oral toxicity (LD50) in rat is 10001 mg/kg.

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

• Keep away from the reach of children

• If the solution comes in contact with eyes, wash your eyes with water immediately ·

• 3. Keep away from light and keep at room temperature• Keep away from combustible material and fire

Metronidazole should not be used in patients with blood dyscrasia. It is suggested that it should not be given in the first three months of pregnancy. When given in conjunction with alcohol, Metronidazole may provoke a disulphiram like effect.

Precautions: Caution is required in the presence of hypersensitivity to Sulphonamides because of possible allergic reactions, in patients with inborn glucose-6-phosphate dehydrogenase deficiency, as haemolysis may occur after the application of the cream to the large body surface area; as well as in the presence of hepatic and renal dysfunction.When treatment with Burnsil cream involves prolonged administration or large burn surfaces, the white blood cell count should be monitored, as leukopenia may occur.

Warning: Elevation of body temperature occurring in children during the first days of treatment is unrelated to Burnsil administration and should not lead to the discontinuation of therapy.

Interaction

Soaps, other anionic agents, borates, bicarbonates, carbonates, chlorides, citrates, nitrates, phosphates & sulfates.

Metronidazole interacts with warfarin, nicoumalone, phenytoin, phenobarbitone, fluorouracil, disulfiram, lithium, cimetidine etc.

Volume of Distribution

Metronidazole is widely distributed throughout the body and various body fluids. They include the bile, saliva, breastmilk, cerebrospinal fluid, and the placenta. Steady-state volume distribution of metronidazole in adults ranges from 0.51 to 1.1 L/kg. It attains 60 to 100% of plasma concentrations in various tissues, such as the central nervous system, however, is not measured in high concentrations in the placental tissue.

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

Topically, chlorhexidine is unlikely to undergo any degree of systemic absorption. Orally administered chlorhexidine, such as that found in oral rinses for dental purposes, is very poorly absorbed from the gastrointestinal tract - the C_max in human subjects following an oral dose of 300mg was 0.206 µg/g and occurred approximately 30 minutes after ingestion (T_max). Following the insertion of 4 PerioChips in 18 adult patients, no detectable plasma or urine chlorhexidine levels were observed.

After the intravenous infusion of a 1.5g dose, peak concentration was reached within 1 hour and was peak level of 30-40 mg/L. When a multiple-dose regimen of 500mg three times a day administered intravenously, steady-state concentrations were achieved within about 3 days and peak concentration was measured at 26 mg/L. When administered orally in the tablet form, metronidazole is absorbed entirely absorbed, showing a bioavailability of greater than 90%. One resource indicates that Cmax after a single oral dose of 500mg metronidazole ranges from 8 to 13 mg/L, with a Tmax of 25 minutes to 4 hours. The AUC following a single 500mg oral dose of metronidazole was 122 ± 10.3 mg/L • h.

A note on the absorption of topical preparations

Insignificant percutaneous absorption of metronidazole occurs after the application of 1% metronidazole cream topically. Healthy volunteers applied one 100 mg dose of 14C-labelled metronidazole 2% cream to unbroken skin. After 12 hours, metronidazole was not detected in the plasma. Approximately 0.1% to 1% of the administered metronidazole was measured in the urine and feces.

Very limited penetration through the skin. Only when applied to very large area burns is absorption into the body generally an issue.

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 metronidazole is 7.3 ± 1.0 after a single 500mg IV dose in healthy subjects. Another resource indicates that the elimination half-life for metronidazole ranges from 6 to 10 hours.

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

Clearance

Dose adjustments may be required in patients with hepatic impairment, as clearance is impaired in these patients. The clearance of metronidazole in the kidneys is estimated at 10 mL/min/1.73 m2. The total clearance from serum is about 2.1 to 6.4 L/h/kg.

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

Elimination Route

Excretion of chlorhexidine gluconate occurs almost exclusively via the feces, with less than 1% of an ingested dose excreted in the urine.

Metronidazole and metabolites are 60 to 80% eliminated in the urine, and 6-15% excreted in the feces.

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

Pregnancy Category B. Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

Not recommended during first & later trimesters. Breast feeding should be delayed until 48 hours after discontinuing metronidazole in the mother.

As Sulphonamide therapy is known to increase the possibility of kernicterus, Silver Sulphadiazine 1% cream should not be used on pregnant women approaching or at term.

Contraindication

Hypersensitivity.

Metronidazole is contraindicated in patients with prior history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.

The use of Burnsil is contraindicated in premature infants and neonates because of possible kernicterus. It should not be used in pregnancy, except in cases when the potentially life-saving benefits of the medication outweigh possible hazards to the foetus

Special Warning

Infant: The cream should not be used on premature infants, or on newborn infants during the first 2 months of life.

Storage Condition

Store in a cool and dry place, protected from light.

Store in a cool and dry place. Protect from light and moisture. Keep out of the reach of children

Innovators Monograph

You find simplified version here Silvonir