Bisacodyl

361.39100

361.39

210-044-4

10X0709Y6I

755914|614826

DTXSID1022681

C28870

WHITE TO OFF-WHITE CRYSTALLINE POWDER IN WHICH PARTICLES HAVING LONGEST DIAMETER SMALLER THAN 50 MICRONS PREDOMINATE|Crystals

A06AB02|A - Alimentary tract and metabolism

2942000000

65.49000

4.11240

1.2 g/cm3

138 °C

492ºC

Soluble in alcohol (slightly), ether (slightly), chloroform, and acetone. Insoluble in water.

2-8ºC

4.8X10-8 mm Hg at 25 deg C /Estimated/

LD50 orally in rats: >3 g/kg (Schmidt)

Tasteless

Henry's Law constant = 7.3X10-12 atm-cu m/mole at 25 °C /Estimated/

193.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 9.7X10-12 cu cm/molec-sec at 25 °C /Estimated/

NONH for all modes of transport

3

R22; R36/37/38

S26-S36

SM8750000

Xi

Stable. Incompatible with strong oxidizing agents.

P305 + P351 + P338

H315-H319-H335

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl bisacodyl, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302 (10.71%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 56 companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

Bisacodyl has not been associated with serum enzyme elevations during therapy or with instances of clinically apparent liver injury.

Milk, antacids, and histamine H2-receptor antagonist such as cimetidine, famotidine, nizatidine or ranitidine may cause the enteric coating to dissolve too rapidly, resulting in gastric or duodenal irritation when administered within one hour of bisacodyl tablets.|Chronic use or over use of laxatives may reduce serum potassium concentrations by by promoting excessive potassium loss from the intestinal tract; may interfer with potassium-retaining effects of potassium sparing diuretics.|In rat colon in situ bisacodyl stimulated biosynthesis of prostaglandin E (PGE). Inhibition of prostaglandin biosynthesis by pretreatment with indomethacin decreased effect of diphenolic laxatives.|Bisacodyl inhibited gastric emptying & motility in rats by activating reflex arising from small intestine. This effect was not prevented by alpha- or beta-sympatholytic, or by parasympatholytic agents. It was antagonized by quinine & quinidine, as well as by chloroquine & mepacrine. Inhibition of gastric motility by cathartics does not appear to be due to an effect on adrenergic or cholinergic pathways but rather involves a purinergic mechanism.

LD50 Dog oral >15 g/kg|LD50 Mouse oral 17.5 g/kg|LD50 Rat oral 4.3 g/kg|LD50 Rat oral >3 g/kg

Bisacodyl's production and use as a laxative(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 85,000(SRC), determined from a structure estimation method(2), indicates that bisacodyl is expected to be immobile in soil(SRC). Volatilization of bisacodyl from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.3X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Bisacodyl is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.8X10-8 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 85,000(SRC), determined from a structure estimation method(2), indicates that bisacodyl is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.3X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). A base-catalyzed second-order hydrolysis rate constant of 2.3 L/mole-sec(SRC) was estimated using a structure estimation method(5); this corresponds to half-lives of 35 and 3.5 days at pH values of 7 and 8, respectively(5). According to a classification scheme(6), an estimated BCF of 78(SRC), from an estimated log Kow of 3.37(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bisacodyl, which has an estimated vapor pressure of 4.8X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase bisacodyl may be removed from the air by wet and dry deposition(SRC). Bisacodyl does not absorb light at wavelengths >290 nm(3) and would not be expected to be susceptible to direct photolysis by sunlight(SRC).

A base-catalyzed second-order hydrolysis rate constant of 2.3 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 35 and 3.5 days at pH values of 7 and 8, respectively(1). Bisacodyl does not absorb light at wavelengths >290 nm(2) and would not be expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 78 was calculated for bisacodyl(SRC), using an estimated log Kow of 3.37(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not altered physically or chemically once released into the environment(SRP).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for bisacodyl can be estimated to be 85,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that bisacodyl is expected to be immobile in soil.

The Henry's Law constant for bisacodyl is estimated as 7.3X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that bisacodyl is expected to be essentially nonvolatile from water surfaces(2). Bisacodyl's Henry's Law constant indicates that volatilization from moist soil surfaces should not occur(SRC). Bisacodyl is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.8X10-8 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to bisacodyl may occur through inhalation of powder and dermal contact with this compound at workplaces where bisacodyl is produced or used. Exposure to the drug among the general population may be limited to those administered bisacodyl (a laxative). (SRC)

Indicated for cleansing of the colon as a preparation for colonoscopy in adults.|FDA Label

Bisacodyl is commonly used, over-the-counter laxative used to treat constipation or bowel irregularity. Bisacodyl has not been associated with serum enzyme elevations during therapy or with clinically apparent liver injury with jaundice.

Gastrointestinal Agents

Cathartics|Oral bulk-forming, lubricant, and stool softener laxatives are indicated prophylactically in patients who should not strain during defecation, such as those with an episiotomy wound, painful thrombosed hemorrhoids, fissures or perianal abscesses, body wall and diaphragmatic hernias , anorectal stenosis, or postmyocardial infarction. /Laxatives; Included in US product labeling/|Oral laxatives are indicated for the short-term relief of constipation. Oral bulk-forming laxatives, stimulant laxatives, and carbon dioxide-releasing suppositories are indicated to facilitate defecation in geriatric patients with diminished colonic motor response... /Laxatives; Included in US product labeling/|Bisacodyl is useful as a laxative for the occasional relief of constipation and in bowel cleansing preparation for x-ray or endoscopic examination. Bisacodyl may be used as a laxative in postoperative, antepartum, or postpartum care or in preparation for delivery|In severe cases of constipation, such as with fecal impaction, mineral oil and stool softener laxatives administered orally or rectally are indicated to soften the impacted feces. To help complete the evacuation of the impacted colon, a rectal stimulant or saline laxative may follow. /Laxatives; Included in US product labeling/

In therapeutic oral doses, all stimulant laxatives may produce some degree of abdominal discomfort, nausea, mild cramps, griping, and/or faintness. Rectal administration of bisacodyl suspensions ... may cause irritation and a sensation of burning of the rectal mucosa and mild proctitis. /Stimulant laxatives/|Weakness, incoordination, and orthostatic hypotension may be exacerbated in elderly patients as a result of significant electrolyte loss when stimulant laxatives are used repeatedly to evacuate the colon. /Stimulant laxatives/|Bisacodyl enteric-coated tablets are not recommenced for children up to 6 years of age since patients in this age group may have difficulty swallowing the tablet without chewing it. Gastric irritation may develop if the enteric coating is destroyed by chewing.|Laxatives should not be given to young children unless prescribed by a physician. Since children are not usually able to describe their symptoms precisely, proper diagnosis should precede the use of laxatives. This will avoid the complication of an existing condition (eg appendicitis) or the appearance of more severe side effects. /Laxatives/|For more Drug Warnings (Complete) data for BISACODYL (12 total), please visit the HSDB record page.

Bisacodyl is hydrolyzed by intestinal brush border enzymes and colonic bacteria to form an active metabolite [bis-(p-hydroxyphenyl) pyridyl-2 methane; (BHPM)] that acts directly on the colonic mucosa to produce colonic peristalsis.

Agents that are used to stimulate evacuation of the bowels. (See all compounds classified as Cathartics.)|Agents that produce a soft formed stool, and relax and loosen the bowels, typically used over a protracted period, to relieve CONSTIPATION. (See all compounds classified as Laxatives.)

15%|primarily in the feces, systemically absorbed drug is excreted in the urine.|Absorption of bisacodyl ... is minimal following oral or rectal administration. Any bisacodyl that is absorbed is metabolized in the liver and excreted in the urine and/or distributed in milk.|Following oral administration of therapeutic dosages of diphenylmethane derivatives, /bowel/ evacuation is produced in 6 to 8 hours. Rectally administered bisacodyl ... produces evacuation of the colon in within 15 minutes to 1 hour.|As much as 5% of orally administered dose is absorbed & excreted in urine as glucuronide.|Excreted primarily in the feces ...|The absorption and plasma level profile and laxative effects of 10 mg bisacodyl as an experimental solution ... in 12 healthy volunteers are described. Results indicate only small amounts of drug were systemically available after administration of /solution/, dragee /(sugar coated capsule)/ and suppository. Urinary excretion was 43.4% for solution, 9.2% for dragee and 3.1% for suppository.

Hepatic (CYP450-mediated).|Following oral or rectal administration bisacodyl is converted to the active desacetyl metabolite bis(p-hydroxyphenyl)pyridyl-2-methane by intestinal and bacterial enzymes.|HPLC method which permits simultaneous detection of bisacodyl (BIS) & its monodesacetylated (mono) as well as totally desacetylated (DES) form, was used to study the intestinal handling of BIS (20 nmol/mL), when incubated for 60 min at the mucosal side of the preparations specified. In jejunal mucosa fluid, BIS disappeared completely in short time, & there was nearly equivalent rise in DES; mono was transitorily present. Hydrolysis was also rapid in mucosal fluid which had been in contact with jejunal sacs for 30 sec, but BIS was stable in blank incubations. Hydrolysis of BIS was slower by colonic than by jejunal sacs, & all 3 forms were present during incubation. It seemed still lower in mucosal fluid which had been in contact with colonic sac for 5 min. BIS & DES accumulate in jejunal & colonic serosal fluid mainly as conjugates (above 95%), & DES was in all cases the only conjugated metabolite present. Accumulation in jejunal serosal fluid was same whether BIS or DES was added.

16 hours

Induces diarrhea which cleanses the colon.|Bisacodyl is a stimulant laxative, ... acting directly on the colonic mucosa-where it stimulates sensory nerve endings to produce parasympathetic reflexes resulting in increased peristaltic contractions of the colon. The contact action of the drug is restricted to the colon, and motility of the small intestine is not appreciably influenced.|/Bisacodyl/ increases water retention in the stool by coating surfaces of stool and intestines with a water-immisicible film. Lubricant effect eases passage of contents through intestines. Emulsification of lubricant tends to enhance its ability to soften stool mass. /Laxatives/|Recent studies show that these drugs alter fluid and electrolyte absorption producing net intestinal fluid accumulation and laxation. Some of these drugs may directly stimulate active intestinal ion secretion. Increased concentrations of cyclic 3',5'-adenosine monophosphate (cAMP), occurring in colonic mucosa cells following administration of stimulant laxatives, may alter the permeability of these cells and mediate active ion secretion thereby producing net fluid accumulation and laxative action. /Stimulant Laxatives/|Bisacodyl caused dose-dependent contractions in isolated guinea pig ileum & taenia coli which was not prevented by atropine or pheniramine. It prevented acetylcholine- & histamine-induced contractions. Bisacodyl-induced contractions were not caused by a decrease in endogenous cyclic amp level. However, both endogenous cyclic amp & verapamil (a calcium transport inhibitor) inhibited bisacodyl-induced contractions, suggesting site of action on calcium-dependent contractile system of smooth muscle cells.|Intestinal secretagogues as well as the laxative, bisacodyl, raise the K+ efflux rate across the mucosal border by 200-300%. Results suggest that laxatives may increase rate of K+ secretion into the colonic lumen by raising the K+ permeability of the mucosal border.

Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ With long term use or overdosage of stimulant laxatives, electrolyte disturbances including hypokalemia, hypocalcemia, metabolic acidosis or alkalosis, abdominal pain, diarrhea, malabsorption, weight loss , and protein-losing enteropathy may occur Electrolyte disturbances may produce vomiting and muscle weakness; rarely osteomalacia, secondary aldosteronism, and tetany may occur. Pathologic changes in including structural damage to the myenteric plexus, severe and permanent interference with colonic motility, and hypertrophy of the muscularis mucosae may occur with chronic use. /Stimulant laxatives/

Agaroletten

ESSENTIALLY 100% AS A CATHARTIC

Complex with tannin: Bisacodyl tannex; Clysodrast.|Bisacodyl is available in an enteric-coated preparation given once daily, the usual oral dose for which is 10 to 15 mg for adults and 5 to 10 mg for children 6 to 12 years old.|Bisacodyl Enema is supplied in a 1.25 fluid ounce (37 mL) ready-to-use squeeze bottle.|/Bisacodyl/ stimulant laxative tablets are supplied in cartons of 25 tablets (5 mg each tablet) wrapped in a foil seal.|Bisacodyl suppositories are supplied in cartons of 4 individually foil-wrapped suppositories.

Phenol, 4,4'-(2-pyridinylmethylene)bis-, 1,1'-diacetate: ACTIVE|Information available in 2005 indicated that Bisacodyl was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Antigua & Barbuda, Argentina, Aruba, Australia, Austria, Bahamas, Bahrain, Bangladesh, Barbados, Belgium, Bermuda, Brazil, Bulgaria, Canada, Cayman Islands, Chile, Colombia, Croatia, Cyprus, Czech Republic, Denmark, Ecuador, Egypt, Finland, France, Germany, Greece, Grenada, Guyana, Haiti, Hong Kong, Hungary, India, Indonesia, Ireland, Iraq, Israel, Italy, Jamaica, Japan, Jordan, Kenya, Kuwait, Lebanon, Libyan Arab Jamahiriya, Luxembourg, Malaysia, Malta, Mauritius, Mexico, Morocco, Netherlands, Netherlands Antilles, New Zealand, Nigeria, Norway, Oman, Poland, Portugal, Qatar, Romania, Russian Federation, Saint Lucia, Saint Vincent & The Grenadines, Saudi Arabia, Singapore, Slovenia, South Africa, Spain, Sweden, Switzerland, Sudan, Syrian Arab Republic, Thailand, Trinidad & Tobago, Tunisia, Turkey, United Arab Emirates, United Kingdom, United States, Yemen, Yugoslavia (1,2)

BISACODYL & ITS HYDROLYSIS PRODUCTS WERE DETECTED AT 254 NM AFTER SEPARATION ON C18 REVERSED-PHASE COLUMN WITH WATER-METHYLCYANIDE-SODIUM ACETATE (60 ML:45 ML:0.300 G) AS MOBILE PHASE. DETECTION LIMITS WERE APPROX 7.5 MUG/ML FOR HYDROLYSIS PRODUCTS & APPROX 15 MUG/ML FOR BISACODYL.|HIGH-PERFORMANCE REVERSED-PHASE LIQUID CHROMATOGRAPHY RETENTION DATA ARE GIVEN. RELATIVE RETENTION TIMES WERE CALCULATED.|Analyte: bisacodyl; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: bisacodyl; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|For more Analytic Laboratory Methods (Complete) data for BISACODYL (13 total), please visit the HSDB record page.

A PROCEDURE WAS DEVELOPED WITH WHICH LAXATIVES CAN BE DETECTED IN URINE. METHOD IS BASED ON HIGH-PERFORMANCE THIN-LAYER CHROMATOGRAPHY IN 2 SYSTEMS AFTER PRETREATMENT OF 20-ML URINE WITH BETA-GLUCURONIDASE & SUBSEQUENT COLUMN EXTRACTION. AT LEAST 32 HR AFTER SINGLE DOSE, BISACODYL CAN BE DETECTED IN URINE. THE METHOD IS HIGHLY SPECIFIC; NONE OF 73 OTHER DRUGS INTERFERED IN EITHER OF THE 2 CHROMATOGRAPHY SYSTEMS.|TLC, GLC OR GC/MS METHODS USED TO DETECT BISACODYL IN URINE.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients