Simethicone

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non Combustible Solids

Simethicone tablets and chewable tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably between 15 - 30 °C. Simethicone oral suspension should be stored in tight, light-resistant containers at a temperature less than 40 °C, preferably between 15- 30 °C; freezing should be avoided.

ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapours, mist or gas.; Environmental precautions: No special environmental precautions required.; Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Appropriate engineering controls: General industrial hygiene practice.

Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Skin protection: Handle with gloves.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

The effect of an antacid on the bioavailability of lithium carbonate was determined in six healthy men in a crossover study. The volunteers were given single 300-mg doses of lithium carbonate alone and with 30 ml of an antacid containing aluminum and magnesium hydroxides with simethicone. Blood samples were collected at various times for 0-24 hours after each dose. The plasma samples were analyzed for lithium using a spectrophotometer, and bioavailability variables were calculated from plasma lithium concentration-time curves. There were no significant differences in peak plasma lithium concentration, time to peak concentration, area under the concentration-time curve from 0 to 24 hours, first-order absorption rate constant, and first-order elimination rate constant between the two treatments. Concurrent administration of antacids and lithium carbonate should not affect lithium blood concentrations.

Carbamazepine is an anticonvulsant drug and is also used as a treatment for patients with manic-depressive illness, post-herpetic neuralgia or phantom limb pain. The drug itself has many drug interactions. Simethicone is an antifoaming agent and is reported to be an inert material with no known drug interaction with carbamazepine. We present a case of a patient who was routinely using carbamazepine 400 mg three times per day and levetiracetam 500 mg twice daily, and experienced carbamazepine overdose after exposure to simethicone. After cessation of simethicone therapy normal drug levels of carbamazepine were obtained again with the standard dose of the drug. The mechanism of interaction is unknown but the risk of overdose should be considered when prescribing simethicone to a patient who is using carbamazepine. Simethicone and carbamazepine, when taken together, may be a cause of carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.

The abilities of antacid (Mylanta II /simethicone/), sucralfate, cimetidine, and ranitidine to protect the gastric mucosa against ethanol-induced necrosis were compared in a standardized, experimental rat model. Fasted rats received pretreatment with either saline, Mylanta II, 500 mg/kg of sucralfate, 50 mg/kg of cimetidine, or 50 mg/kg of ranitidine. This was followed one hour later by intragastric administration of 2 mL of 100 percent ethanol. Gastric mucosal injury was assessed four hours after administration of ethanol by quantitation of gross mucosal necrosis, assessment of mucosal histology, and determination of intragastric blood and protein concentrations. Pretreatment with Mylanta II or sucralfate significantly reduced ethanol-induced gastric mucosal necrosis. The protective effect of sucralfate was six to 10 times greater than that of Mylanta II. H2-receptor antagonists increased ethanol-induced gastric mucosal necrosis.

Alverine, an antispasmodic agent for the treatment of irritable bowel syndrome (IBS), may be combined with simethicone, a protective agent of the mucosa. Stress is a major factor triggering abdominal pain in IBS and causing hypersensitivity to colonic distension in animals through an increased colonic permeability. The antinociceptive effects of alverine and simethicone, separately or in association, were evaluated on stress-induced colonic hypersensitivity to distension in rats. The influence of simethicone on altered permeability was also tested. Groups of 8-10 female adult Wistar rats (200-250 g) housed individually were used. Gut paracellular permeability was evaluated after 2 hr of partial restraint stress using oral gavage with (51)Cr-EDTA and 24 hr of urine collection. The number of abdominal cramps during colonic distension was evaluated in animals equipped with electrodes on their abdominal striated muscles. At 200 mg/kg p.o. twice a day, but not at lower doses, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. Administered alone at 10 mg/kg p.o., alverine also reduced stress-induced hypersensitivity to distension; lower doses were inactive. However, alverine administered at an inactive dose with simethicone suppressed stress-induced hypersensitivity to distension. We conclude that both simethicone and alverine have visceral antinociceptive effects by two different mechanisms and that simethicone exerts a potentiating effect on the antinociceptive action of alverine.

LC50; Species: Daphnia magna (Water flea) age 1-48 hr, 1st instar; Conditions: freshwater, flow through, 18 °C, pH 8.8-9.3, hardness 182-204 mg/L CaCO3, alkalinity 98-99 mg/L CaCO3, dissolved oxygen 8.6-9.0 mg/L; Concentration: 245000 ug/L for 48 hr (95% confidence interval: 177000-338000 ug/L) /30% Dow Corning Antifoam A/

LC50; Species: Daphnia magna (Water flea) age 1-48 hr, 1st instar; Conditions: freshwater, flow through, 18 °C, pH 8.8-9.3, hardness 182-204 mg/L CaCO3, alkalinity 98-99 mg/L CaCO3, dissolved oxygen 8.6-9.0 mg/L; Concentration: 73400 ug/L for 48 hr (95% confidence interval: 53200-101000 ug/L) /30% Dow Corning Antifoam A/

LC50; Species: Pachygrapsus crassipes (Shore crab) length 50-80 mm; Conditions: freshwater, static, 24 °C; Concentration: >10000000 ug/L for 96 hr /30% Dow Corning Antifoam A/

LC50; Species: Penaeus sp. (Penaeidean shrimp) length 8-12 mm Penaeus oxtecus; Conditions: saltwater, static, 21 °C, salinity 27.2 ppt; Concentration: >1000000 ug/L for 96 hr /28.8% purity/

For more Ecotoxicity Values (Complete) data for Simethicone (8 total), please visit the HSDB record page.

Simethicone does not have any serious side effects. There have been reports of mild diarrhea and nausea. Since simethicone is not absorbed orally, it is logical that systemic side effects such as kidney injury, hypertension, and hyperglycemia do not occur. Silicosis is a condition of pulmonary fibrosis caused by the inhalation of silica dust (also known as silicon dioxide). Still, there have been no reported cases of silicosis secondary to oral simethicone administration.

IDENTIFICATION AND USE: Simethicone is a gray, translucent, viscous liquid. Simethicone is used in the production of anti-gas tablets; lubrication and bubble free application of topical preparations; anti-whitening properties in acne and other dermatological ointments, creams and lotions; as an antifoaming agent in the manufacture of drug products made by microbial fermentations; it is used in cosmetic and toiletry products. HUMAN EXPOSURE AND TOXICITY: Unrelated case reports have been documented where simethicone was administered in conjunction with another drug as part of a prescribed treatment and an adverse event occurred. The incidences of pulmonary aspiration of gastric contents and apnea did not indicate that simethicone alone was the cause of the adverse event. The two cases of overdose were not intentional but due to incorrect dosing instructions or unknown drug interaction. ANIMAL STUDIES: In studies on the treatment of irritable bowel syndrome with rats, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. In developmental toxicity study it was found that oral administration of food grade simethicone during organogenesis produced no developmental effects including teratogenicity in rabbits at dietary levels up to 2.5%.

Simethicone is not absorbed systemically, so it is safe in pregnancy and breastfeeding. There is no treatment for a simethicone overdose other than stopping the medication.

/HUMAN EXPOSURE STUDIES/ Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit. To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS, we carried out a systematic review and meta-analysis of randomized controlled clinical trials on antispasmodic agents for IBS treatment. Clinical trials identified from January 1960 to May 2011 were searched for in MEDLINE, the Cochrane Library, and in the ClinicalTrials.gov registry. Treatment response was evaluated by global improvement of symptoms or abdominal pain, abdominal distention/bloating, and frequency of adverse events. The effect of antispasmodics vs placebo was expressed in OR and 95% CI.Twenty-seven studies were identified, 23 of which fulfilled inclusion criteria. The studied agents were pinaverium bromide, mebeverine, otilonium, trimebutine, alverine, hyoscine, alverine/simethicone, pinaverium/simethicone, fenoverine, and dicyclomine. A total of 2585 patients were included in the meta-analysis. Global improvement was 1.55 (CI 95%: 1.33 to 1.83). Otilonium and the alverine/simethicone combination produced significant values in global improvement while the pinaverium/simethicone combination showed improvement in bloating. As for pain, 2394 patients were included with an OR of 1.52 (IC 95%: 1.28 a 1.80), favoring antispasmodics. Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations.

/HUMAN EXPOSURE STUDIES/ The results of studies of the effect of simethicone on abdominal gas-related symptoms have been contradictory. In a randomized, double-blind, cross-over study, ten healthy volunteers were given 30 g lactulose and 600 mg simethicone or placebo. End-expiratory breath samples were collected and analyzed for H2, and gastrointestinal symptoms registered. There were no differences in biochemical parameters or symptom score between simethicone and placebo. In contrast to previous studies, we used a sufficiently large dose of lactulose to produce gastrointestinal symptoms, a higher dose of simethicone and placebo tablets containing the same additives as the simethicone tablets. There was no demonstrable effect of simethicone on symptoms or intestinal gas production caused by carbohydrate malabsorption.

/HUMAN EXPOSURE STUDIES/ Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that affects 15-20% of the Western population. BACKGROUND: There are currently few therapeutic options available for the treatment of IBS. The aim of this study is to evaluate the efficacy and the safety of a medical device containing a combination of Simethicone and Bacillus coagulans in the treatment of IBS. This is a monocentric double-blind, placebo-controlled parallel group clinical trial. Adult subjects suffering from IBS as defined by Rome III criteria were enrolled. Bloating, discomfort, abdominal pain were assessed as primary end point. Subjects received the active treatment or placebo 3 time a day after each meal for 4 weeks of study period. Subjects were submitted to visit at Day 0 (T1), at Days 14 (T2) and 29 (T3). Fifty-two patients were included into the study. Intragroup analysis showed a significant reduction of the bloating, discomfort and pain in Colinox group (CG) compared to placebo group (PG). Between group analysis confirmed, at T1-T3, significant differences between CG and PG in bloating and discomfort. Simethicone is an inert antifoaming able to reduce bloating, abdominal discomfort. Literature offers increasing evidence linking alterations in the gastrointestinal microbiota and IBS and it is well known that probiotics are important to restore the native gut microbiota. The Colinox medical device is specifically targeted against most intrusive symptom of IBS (bloating) and it is also able to counteract the most accredited ethiopathogenetic factor in IBS (alterations of intestinal microbiota). This is the first randomized double-blind placebo-controlled clinical trial demonstrating the efficacy and safety of a combination of simethicone and Bacillus coagulans in treatment of IBS.

Simethicone's production and use in personal care products such cosmetics, ointments and skin protectants(1,2), as an anti-foaming agent(1) and as an antiflatulent(1) may result in its release to the environment through various waste streams(SRC). The greatest potential source of polydimethylsiloxane fluids release to marine environments is from consumer products and process aids discarded to wastewater, rather than from manufacture(3). Approximately 14% of the polydimethylsiloxanes manufactured are disposed of down the drain, where they enter wastewater treatment systems(4).

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

simethicone

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ Alverine, an antispasmodic agent for the treatment of irritable bowel syndrome (IBS), may be combined with simethicone, a protective agent of the mucosa. Stress is a major factor triggering abdominal pain in IBS and causing hypersensitivity to colonic distension in animals through an increased colonic permeability. The antinociceptive effects of alverine and simethicone, separately or in association, were evaluated on stress-induced colonic hypersensitivity to distension in rats. The influence of simethicone on altered permeability was also tested. Groups of 8-10 female adult Wistar rats (200-250 g) housed individually were used. Gut paracellular permeability was evaluated after 2 hr of partial restraint stress using oral gavage with (51)Cr-EDTA and 24 hr of urine collection. The number of abdominal cramps during colonic distension was evaluated in animals equipped with electrodes on their abdominal striated muscles. At 200 mg/kg p.o. twice a day, but not at lower doses, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. Administered alone at 10 mg/kg p.o., alverine also reduced stress-induced hypersensitivity to distension; lower doses were inactive. However, alverine administered at an inactive dose with simethicone suppressed stress-induced hypersensitivity to distension. We conclude that both simethicone and alverine have visceral antinociceptive effects by two different mechanisms and that simethicone exerts a potentiating effect on the antinociceptive action of alverine.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Dow Corning Antifoam A /(simethicone)/ compound, a food grade polydimethylsiloxane was evaluated for its developmental toxicity potential in New Zealand White rabbits. Time-mated female rabbits were fed Antifoam A compound in the diet at concentrations of 0, 0.5, 1.0, and 2.5% from the morning of day 6 through the morning of day 19 of gestation. Clinical signs of toxicity in the females were monitored daily during treatment. At termination (gd 29), confirmed-pregnant females (20-22 per group) were evaluated for gestational outcome; each live fetus was examined for external, visceral and skeletal malformations. There were no overt signs of toxicity in the dams, and no statistically significant differences in food consumption were observed between treated and control rabbits. No adverse effects were noted in mean maternal body weight or liver weight. The incidence of resorptions among the total fetal population was not altered by feeding Antifoam A compound. Male and female pup weights were not affected by the maternal treatment. There were no significant treatment related adverse effects in the incidence of external, visceral or skeletal abnormalities. In summary, oral administration of food grade polydimethylsiloxane during organogenesis produced no developmental effects including teratogenicity in rabbits at dietary levels up to 2.5%.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 90,652 workers (75,193 of these were female) were potentially exposed to simethicone in the US(1). Occupational exposure to simethicone may occur through dermal contact with this compound at workplaces where simethicone is produced or used. Use data indicate that the general population may be exposed to simethicone via ingestion of drugs (anti-flatulents) and dermal contact with this consumer products containing simethicone(SRC).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: simethicone is included in external analgesic drug products.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: simethicone is included in skin protectant drug products.

Antiflatulent active ingredients. Simethicone; maximum daily dose 500 mg. There is no dosage limitation at this time for professional labeling.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed over-the-counter drug products, including simethicone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The main use of simethicone as an excipient is as an antifoaming agent in pharmaceutical manufacturing processes ... .

A poly(dimethylsiloxane) which is a polymer of 200-350 units of dimethylsiloxane, along with added silica gel. It is used as an antiflatulent, surfactant, and ointment base.

Antifoaming ingredient in cosmetics

Simethicone manufactured under the name of MED-340 is used in the production of anti-gas tablets; lubrication and bubble free application of topical preparations; anti-whitening properties in acne and other dermatological ointments, creams and lotions; as an antifoam in the manufacture of drug products made by microbial fermentations; listed in the INCI index for use in cosmetic and toiletry products.

For more Uses (Complete) data for Simethicone (6 total), please visit the HSDB record page.

Silicone dioxide is initially rendered hydrophobic in one of a variety of proprietary processes specific to a particular manufacturer. It is then slowly mixed with the silicone fluids in a formulation. After mixing, the simethicone is milled to ensure uniformity.

Antifoam A, Baros, Colicon, Endo-Paractol, Gas-X, Infacol, Lefax, Mylicon, Phasil, Phazyne, sab simplex; Silain.

Table: Simethicone Combinations [Table#4658]

Table: Simethicone Preparations [Table#4659]

Simethicone is a mixture of fully methylated linear siloxane polymers containing repeating units of polydimethylsiloxane, stabilized with trimethylsiloxy end-blocking units, and silicon dioxide. Simethicone contains 90.5-99% of polydimethylsiloxane and 4-7% silicon dioxide.

Food Additives -> ANTICAKING_AGENT; ANTIFOAMING_AGENT -> JECFA Functional Classes

Food Additives -> ANTICAKING_AGENT; ANTIFOAMING_AGENT -> JECFA Functional Classes

Food Additives -> ANTICAKING_AGENT; ANTIFOAMING_AGENT -> JECFA Functional Classes

Cosmetics -> Emollient; Skin conditioning; Antifoaming; Hair conditioning

Not Known or Reasonably Ascertainable

Dimethecone mixed with silicon dioxide is known as simethicone

The defoaming power of simethicone, when assoc with antacid, is more pronounced in suspension than in tablets. Incorporation of lactose in tablets enhances the defoaming efficiency. Antiflatulent-antispasmodic digestive tablets (simethicone, belladonna ext, pepsin, pancreatin, and dehydrocholic acid) achieve a mild decrease in their defoaming efficiency when stored for 360 days at 25 °C. Pepsin shows a reduction in its activity in tablets with simethicone while pancreatin achieves relatively greater stability with simethicone. The stability of total alkaloid content of belladonna is also improved with simethicone.

Average number of dimethylsiloxane units is 200 to 350.

NuSil currently manufactures a simethicone product line consisting of the MED-340 Simethicone USP (100%), MED-341 Simethicone Emulsion USP (30%), and the MED-342 Simethicone GS (30% granular solid). The MED-340 and MED-341 are USP monographed products while the MED-342 is a mixture of simethicone USP and a maltodextrin substrate.