Calderm

Uses

Dimethicone is an ingredient used to treat dry and irritated eyes.

Dimethicone is a colorless liquid with both cosmetic and therapeutic uses. It is used in topical creams and ointments to help distribute the active ingredients. Dimethicone is used as an anti-foaming agent, a hair and skin conditioner, and in the treatment of head lice and, as an anti-bloating/anti-flatulence agent , .

Sucralfate tablet is used for the treatment of acute, nonmalignant gastric and duodenal ulcers. Maintenance therapy to prevent the recurrence of duodenal ulcers.

Sucralfate suspension is used for the short-term (up to 8 weeks) treatment of active duodenal ulcer.

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 .

Calderm is also used to associated treatment for these conditions: Acute Diarrhoea, Aerophagy, Dry Skin, Duodenal Ulcer, Dyspepsia, Flatulence, Gastric Ulcer, Gastritis, Gastro-esophageal Reflux Disease (GERD), Hiatus Hernia, Pancreatic Insufficiency, Post Operative Gas, Pre-operative Gas, Stress Ulcers, Bowel preparation therapy, Carbohydrate Digestion, Digestive Aid, Fat Digestion, Protein DigestionDyspepsia, Gastric Ulcer, Gastritis, Gastro-esophageal Reflux Disease (GERD), Healing, Mucositis, Peptic Ulcer, Stress Ulcers, Active Duodenal ulcer, Antiplatelet TherapyCandidiasis, 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 Calderm works

When applied topically, dimethicone forms a layer to delay the evaporation of water . In the treatment of head lice dimethicone 100, the respiratory systems of head lice are targeted. NYDA works by suffocating the lice, nymphs and the embryos. The physical properties of this drug, including the viscosity and spreading property of the solution allow it to easily flow into the respiratory system of all developmental stages of the insect, causing suffocation and death of the organisms. It diffuses through the stigmata (spiracles) of the lice, into the tracheae of the head lice as well as through the aeropyles of the egg operculum. The solution then displaces oxygen. The low viscosity, volatile dimethicone enables the NYDA head lice solution to penetrate into the breathing system. Its evaporation causes the thickening of the NYDA solution. The remaining high viscosity dimethicone ultimately encloses the respiratory system and thus leading to suffocation of all stages of head lice (adult lice, larvae and eggs). This mode of action prevents the development of lice resistance by preventing the formation of new progency .

Studies performed using house crickets and lice suggest a close correlation between the death of the lice and the influx of the solution into the insect head tracheae. These data strongly suggest that the total filling of the head tracheae immediately blocks the oxygen supply to the insect central nervous system. Death, following numerous stages of disability after the entrance of dimethicones into the abdominal tracheal system, demonstrates the sequence of oxygen deprivation. NYDA was applied directly to the head and mouth of the organism, and was found to have no effect when applied solely to the outside of the head/mouth .

The mechanism of action of this drug in the healing duodenal ulcers is not yet completely defined, however, there are several probable mechanisms that adequately describe the healing activity of sucralfate. There is evidence that sucralfate acts locally to aid in tissue healing, and not systemically .

Studies in both humans and animals have indicated that sucralfate forms a complex that binds to protein-rich exudate found on the surface of ulcers. It binds to albumin and fibrinogen preventing blood clot lysis by stomach acid (hydrochloric acid). Sucralfate increases the tissue levels of fibroblast growth factors and epidermal growth factors , leading to an increase in prostaglandins at the gastrointestinal tract lining, which promote the healing of gastrointestinal ulcers .

In the laboratory setting, a sucralfate-albumin film provides a barrier against the entry of hydrogen ions, which are a component of gastric acid. In humans, sucralfate, given at therapeutic doses for ulcers, decreases pepsin activity in gastric fluids by 32% . Pepsin has been shown to be damaging to tissues, further aggravating ulcer lesion inflammation . Bile salts have been implicated in mucosal injury to the gastrointestinal tract . Sucralfate has also been shown to adsorb bile salts in the laboratory, setting, which could further contribute to its beneficial effects in ulcer healing .

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

Calderm dosage

Adult: Usual dose 1 gm 4 times daily to be taken 1 hour before meals and at bed time. Maximum daily dose is 8 gm. Four to six weeks treatment is usually needed for ulcer healing but upto twelve weeks may be necessary in resistant cases. Antacids may be used as required for relief of pain, but should not be taken half an hour before or after Gastalfet.

Elderly: There are no special dosage requirements for elderly patients but as with all medicines the lowest effective dose should be used.

children: Safety and efficacy in children have not been established

Side Effects

The incidence and severity of side effects from sucralfate are very low. Mild side effect like constipation has been reported in some patients.

Toxicity

The minimum lethal oral dose of dimethicone 200 (50 cs), dimethicone 550 (75 cs), dimethicone in rats .

A 76-week dietary toxicity study of a silicone antifoam compound (94% polydimethylsiloxane silicone oil and 6% silicone dioxide) was performed in mice. Three groups were given diet containing 0, 0.25%, or 2.5% of the test article. The dose levels in the treatment groups were estimated to be 580 and 5800 mg/kg/day. Mortality was increased in the 5800 mg/kg/day females. No target organs of toxicity were observed. The no-effect dose was 580 mg/kg/day. This study is of limited usefulness for assessing the toxicity of dimethicones, due to the small number of organs/tissues that were examined .

In one clinical study, 145 subjects were treated with either NYDA (dimethicone )or with a permethrin-based lice product. The number of subjects experiencing any adverse events was similar in both groups. In the NYDA group, 29 adverse events were reported in 25 subjects. All except two adverse events were categorized as being unrelated to the lice treatment (e.g., superficial wound after a fall, otitis externa following swimming in a pool). Two patients in the NYDA group experienced ocular irritation after treatment when the product entered the eyes. The irritation resolved spontaneously in both cases after rinsing the eyes with clean water .

Overdose

Overdosage has never been observed with sucralfate . It is unlikely, as administering a maximum dose of up to 12 g/kg/body weight in several animal species did not result in death. The lethal dose could not be determined in these studies . It is likely that overdose of sucralfate in humans would result in constipation, and supportive treatment would be advised .

Use in pregnancy

This drug is considered a pregnancy Category B drug. Studies have been performed in rodents and rabbits at doses up to 50 times the recommended human dose. No harm to the fetus has been observed in the abovementioned studies. Sufficient and well-controlled clinical trials have not been performed in pregnant women. Due to the fact that the results of animal studies are not always relevant to human response, sucralfate should be used during pregnancy only if it is deemed essential for the mother's health .

Use in nursing

Whether this drug is excreted in human milk is currently unknown. Many drugs are excreted in breast milk, therefore, if sucralfate is administered to a lactating and nursing woman, caution should be observed .

Carcinogenesis

24 month toxicity studies were performed in rodents, and the dose of sucralfate reached up to 1 g/kg (equivalent to 12 times the recommended human dose). No signs of sucralfate-related tumors were noted.

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

The product should only be used with caution in patients with renal dysfunction

Interaction

Concomitant use of sucralfate may reduce the bioavailability of certain drugs as has been observed in animal studies with tetracycline, phenytoin and cimetidine and in human studies with digoxin. Administration of sucralfate with any of these drugs should be separated by two hours. Since sucralfate may hinder warfarin absorption, caution should be exercised when these two drugs are used together.

Volume of Distribution

Following injection of [14C]dimethicone fluid in the hind limb of rats, the radioactivity was distributed primarily in the gastrointestinal tract, and no evidence of metabolism was observed. When [14C]dimethicone was administered through i.p. injection in rats, the following distribution of radioactivity was observed at 25 days after dosing: 51% in adipose tissue, 27% in gastrointestinal tissues, and 15% in liver .

This drug is absorbed in a very small quantity, and normally localizes to inflamed gastrointestinal lesions .

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

This drug is not believed to be absorbed when used in quantities from 1-30% .

This drug is absorbed from the gastrointestinal tract in very minimal quantities . The adsorbed sulfated disaccharide is excreted in the urine . This drug contains aluminum and after the administration of 1 g of sucralfate 4 times per day, about 0.001% to 0.017% of this aluminum content is absorbed in patients with normal renal function . This number is expected to increase in those with impaired renal function .

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 half-life is not known. In animals, the elimination half-life of the sucrose component of this drug is from 6-20 h .

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

Clearance

Sucralfate contains aluminum. The administration of sucralfate in non-dialyzed chronic renal failure patients warrants careful consideration from the treating physician as the excretion of absorbed aluminum may be decreased, causing possible aluminum toxicity .

In dialyzed patients diagnosed with chronic renal failure, aluminum toxicity related to sucralfate has been observed and reported. The daily amount of aluminum ingestion (including sucralfate) should be carefully examined before administering sucralfate in combination with other drugs also containing aluminum, including various antacids .

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

Elimination Route

The negligible amount of this drug that is absorbed is excreted mainly in the urine within 48 hours .

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

Although animal studies show no evidence of foetal malformation, safety in pregnant women has not been established and Sucralfate should be used in pregnancy only if clearly needed.

It is not known whether this drug is excreted in human milk. Caution should be exercised when sucralfate is administered to nursing mothers.

Contraindication

There are no known contraindications

Acute Overdose

There is no experience in human with overdosage

Storage Condition

Store at 20-25° C.

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