Docusate

Docusate
Docusate sodium
Names
Trade namesColace, Ex-Lax Stool Softener, others
IUPAC name
  • Sodium 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate
Clinical data
Drug classStool softener
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: C (Risk not ruled out)[1]
    Routes of
    use
    By mouth or rectally
    Onset of action12 hrs to 5 days[2]
    Duration of action3 days[2]
    Defined daily dose0.15 g (by mouth)[3]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa601113
    Legal
    License data
    Legal status
    Chemical and physical data
    FormulaC20H37NaO7S
    Molar mass444.56 g·mol−1
    3D model (JSmol)
    Density1.1 g/cm3
    Melting point153 to 157 °C (307 to 315 °F)
    Solubility in water1 in 70 parts mg/mL (20 °C)
    SMILES
    • [Na+].[O-]S(=O)(=O)C(C(=O)OCC(CC)CCCC)CC(=O)OCC(CC)CCCC
    InChI
    • InChI=1S/C20H38O7S.Na/c1-5-9-11-16(7-3)14-26-19(21)13-18(28(23,24)25)20(22)27-15-17(8-4)12-10-6-2;/h16-18H,5-15H2,1-4H3,(H,23,24,25);/q;+1/p-1
    • Key:APSBXTVYXVQYAB-UHFFFAOYSA-M

    Docusate, also known as docusate salts or dioctyl sulfosuccinate,[4] is a laxative of the stool softener type used to treat constipation.[2] It is considered a good choice in children who have hard feces.[2] Use for constipation, however, is poorly supported by evidence.[5][6] It may be taken by mouth or used rectally.[2] By mouth a bowel movement often occurs in 1 to 3 days,[2] while rectal use may be effective within 20 minutes.[7]

    Side effects are uncommon.[2] Rarely, there may be abdominal cramps or diarrhea.[2] Efficacy decreases with long-term use, and may cause poor bowel function.[1] Docusate is acceptable during pregnancy and breastfeeding.[8] It works by allowing more water to be absorbed by the feces.[1][9] It typically comes in the form of a sodium, calcium, or potassium salt.[2]

    It is on the World Health Organization's List of Essential Medicines.[10] It is available as a generic medication and is not very expensive.[9] In the United States, one hundred doses are about US$14.[2] The sodium salt, dioctyl sodium sulfosuccinate, also is used as a food additive, emulsifier, dispersant, and wetting agent, among other uses.[11] In 2016 it was the 127th most prescribed medication in the United States with more than 5 million prescriptions.[12]

    Medical use

    Constipation

    Docusate is frequently used to treat constipation, and in painful anorectal conditions such as hemorrhoids and anal fissures, to help avoid pain caused by straining during bowel movements. However, the available evidence does not support its use for these purposes.[13] Multiple studies have found docusate to be no more effective than a placebo for improving constipation.[5][6][14][15] Others have found it to be less useful for the treatment of chronic constipation than psyllium.[16]

    The medication may be given to people who are receiving opioid medication, although prolonged use may cause irritation of the gastrointestinal tract. Data supporting its efficacy in treating chronic constipation are lacking.[15][17]

    Other

    Docusate sodium, when used with ear syringing, may help with earwax removal, particularly in the case of impaction.[18]

    Docusate sodium is approved and recommended as safe during pregnancy and breastfeeding.[19]

    Dosage

    The defined daily dose is 0.15 g (by mouth).[3] The typically dose in adults is 12.5 to 50 mg two to four times per day.[20]

    Docusate sodium may be given by mouth or rectally. It also is used as an emulsifier and dispersant in topical preparations. When taken by mouth it is typically recommended with plenty of water.

    Side effects

    Side effects are typically mild and include stomach pain, diarrhea, or cramping. Serious allergic reactions may occur with the drug. The most severe side effect of docusate, although very rare, is rectal bleeding.[21]

    Docusate is not recommended in people with appendicitis, acute abdomen, or ileus.[17]

    Dioctyl sodium sulfosuccinate is a strong irritant for eyes and lungs, and also a skin irritant. Ingestion may cause the side effects described above, such as diarrhea, intestinal bloating, and occasionally cramping pains. Dioctyl sodium sulfosuccinate is not known to be carcinogenic, mutagenic, or teratogenic.[22]

    Interactions

    Docusate might increase resorption of other drugs, for example, dantron (1,8-dihydroxyanthraquinone).[17]

    Chemistry

    Solubility of dioctyl sodium sulfosuccinate in water is 1:70 (14 g/l) at 25 °C, increasing to 1:20 at 70 °C. Solubility is better in less polar solvents: 1:30 in ethanol, 1:1 in chloroform and diethylether, and practically unlimited in petroleum ether (25 °C). It also is highly soluble in glycerol, although this is a rather polar solvent.

    The ester groups are easily cleaved under basic conditions, but are stable against acids.[17]

    Docusate salts include docusate calcium, docusate sodium, and docusate potassium.[1][4]

    Mechanism of action

    Docusate does not stay in the gastrointestinal tract, but is absorbed into the bloodstream and excreted via the gallbladder[17] after undergoing extensive metabolism.

    The effect of docusate may not necessarily be all due to its surfactant properties. Perfusion studies suggest that docusate inhibits fluid absorption or stimulates secretion in the portion of the small intestine known as the jejunum.

    Society and culture

    Cost

    It is available as a generic medication and is not very expensive.[9] In the United States, one hundred doses are about US$14.[2] In 2016 it was the 127th most prescribed medication in the United States with more than 5 million prescriptions.[12]

    Other uses

    Dioctyl sodium sulfosuccinate is used as a surfactant in a wide range of applications, often under the name Aerosol-OT. It is unusual in that it is able to form microemulsions without the use of co-surfactants, and it has a rich variety of aqueous-phase behavior including multiple liquid crystalline phases.[23]

    • It is used as an excipient in the production of tablets (as a lubricant) and suspensions (as an emulsifier).[24]
    • It is the most widely used surfactant in reverse micelle encapsulation studies.[25]

    Dioctyl sodium sulfosuccinate is approved for use in a variety of food products. It is approved for use as a surface active agent, stabilizer, thickener, wetting agent, processing aid, solubilizing agent, emulsifying agent, and dispersing agent in foods. The highest amount found in food products is 0.5% by weight, which include pasteurized cheese spreads, cream cheeses and salad dressings.[26]

    The FDA determined that dioctyl sodium sulfosuccinate is generally recognized as safe (GRAS) for use as wetting agents or solubilizers for flavor emulsion stabilizers in carbonated and non-carbonated drinks at levels up to 10 parts per million.[27]

    Brandnames

    An example of a stool softener

    In the U.S., dioctyl sodium sulfosuccinate is available under multiple brand names: Aqualax, Calube, Colace, Colace Micro-Enema, Correctol Softgel Extra Gentle, DC-240, Dialose, Diocto, Dioctocal, Dioctosoftez, Dioctyn, Dionex, Doc-Q-Lace, Docu Soft, Docucal, Doculax, Docusoft S, DOK, DOS, Doss-Relief, DSS, Dulcolax - Stool Softener (not to be confused with another drug marketed under the Dulcolax brand, bisacodyl, which is a stimulant laxative), Ex-Lax Stool Softener, Fleet Sof-Lax, Genasoft, Kasof, Laxa-basic, Modane Soft, Octycine-100, Pedia-Lax, Preferred Plus Pharmacy Stool Softener, Regulax SS, Sulfalax Calcium, Sur-Q-Lax, Surfak Stool Softener, and Therevac-SB. Generic preparations are also available.

    In the UK, dioctyl sodium sulfosuccinate is sold under the brand name Docusol (Typharm Ltd) and DulcoEase (Boehringer Ingelheim).

    In Australia, dioctyl sodium sulfosuccinate is sold as Coloxyl and Coloxyl with senna.

    In India, preparations include Laxatin by Alembic, Doslax by Raptakos Laboratories, Cellubril by AstraZeneca, and Laxicon by Stadmed.

    Other animals

    Toxicity for different species varies widely, but dioctyl sulfosuccinate biodegrades quickly in soil and water, a typical finding being >90% in 12 to 17 days. In the atmosphere, it is predicted to be removed by a photochemical reaction with an estimated half-life of 18 hours.[28]

    Marine species

    Dioctyl sodium sulfosuccinate has been determined to be of low toxicity for crustaceans such as the hermit crab Clibanarius erythropus and the shrimp Crangon crangon.

    Toxicity for molluscs varies widely, with 48-hour LD50 found between 5 mg/l for the common limpet and 100 mg/l for the common periwinkle. Various species of phytoplankton have an LD50 around 8 mg/l.

    In a 2010 study, dioctyl sodium sulfosuccinate exhibited higher toxicity against bacteria (Vibrio fischeri, Anabaena sp.) and algae (Pseudokirchneriella subcapitata) than did a number of fluorinated surfactants (PFOS, PFOA, or PFBS). Measuring bioluminescence inhibition of the bacteria and growth inhibition of the algae, the ED50 were in the range of 43–75 mg/l. Combinations of the fluorinated compounds with dioctyl sodium sulfosuccinate showed mid to highly synergistic effects in most settings, meaning that such combinations are significantly more toxic than the individual substances.[29]

    Freshwater species

    The substance is highly toxic for rainbow trout with a median lethal concentration (LC50) of 0.56 mg/l after 48 hours for the pure substance. It is only slightly to moderately toxic for rainbow trout fingerlings, and slightly toxic for harlequin rasboras (LC50 27 mg/l of a 60% formulation after 48 hours).

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