Dicycloverine

Dicycloverine
Names
Trade namesByclomine, Bentyl, Dibent, others
IUPAC name
  • 2-(Diethylamino)ethyl 1-cyclohexylcyclohexane-1-carboxylate
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
    Defined daily dose80 mg[1]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa684007
    Legal
    License data
    Legal status
    Pharmacokinetics
    Protein binding>99%
    Elimination half-life5 h
    Chemical and physical data
    FormulaC19H35NO2
    Molar mass309.494 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C(OCCN(CC)CC)C1(CCCCC1)C2CCCCC2
    InChI
    • InChI=1S/C19H35NO2/c1-3-20(4-2)15-16-22-18(21)19(13-9-6-10-14-19)17-11-7-5-8-12-17/h17H,3-16H2,1-2H3 checkY
    • Key:CURUTKGFNZGFSE-UHFFFAOYSA-N checkY

    Dicycloverine, also known as dicyclomine, is a medication that is used to treat spasms of the intestines such as occur in irritable bowel syndrome.[2][3] It is taken by mouth or by injection into a muscle.[3] While it has been used in baby colic and enterocolitis, evidence does not support these uses.[3]

    Common side effects include dry mouth, blurry vision, weakness, sleepiness, and lightheadedness.[3] Serious side effects may include psychosis and breathing problems in babies.[3] Use in pregnancy appears to be safe while use during breastfeeding is not recommended.[4] How it works is not entirely clear.[3]

    Dicycloverine was approved for medical use in the United States in 1950.[3] It is available as a generic medication.[2] In the United Kingdom the NHS pays about 1.84 £ per dose as of 2019.[2] In the United States the wholesale cost of this amount is about US$0.15.[5] In 2017, it was the 181st most commonly prescribed medication in the United States, with more than three million prescriptions.[6][7]

    Medical uses

    Dicyclomine is used to treat the symptoms of irritable bowel syndrome, specifically hypermotility, in adults.[8][9] As of 2016, clinical guidelines recommended dicycloverine and other antispasmodics for IBS with diarrhea as a first line treatment, although the evidence for their effectiveness was very weak.[8]

    Dosage

    The defined daily dose is 80 mg by mouth or by injection.[1]

    ASide effects

    Dicycloverine can cause a range of anticholinergic side effects such as dry mouth, nausea, blurred vision, dizziness, confusion, severe constipation, stomach pain, heart palpitations, difficulty urinating, and seizures.[8]

    This medicine should not be used for people who have an obstructive GI or urinary condition, severe ulcerative colitis, reflux, any unstable cardiac condition, glaucoma, myasthenia gravis, and anyone who is acutely bleeding.[9]

    It should not be given to children or infants with colic due to the risks of convulsions, difficult breathing, irritability, and restlessness,[10] and there is little evidence to support the efficacy in such use in any case.[11]

    Because dicycloverine is known to impair thinking and coordination, people taking the drug should avoid driving or operating machinery.[9]

    Pregnancy and breastfeeding

    The effect on the baby during pregnancy or breastfeeding is not well understood.[9]

    Pharmacology

    Dicycloverine blocks the action of acetylcholine on cholinergic receptors on smooth muscles in the GI tract, relaxing the smooth muscle.[8]

    History

    A 10-mg oral capsule of dicyclomine hydrochloride

    Dicycloverine was first synthesized chemically in the United States circa 1945 by scientists at William S. Merrell Company.[12]

    It was first marketed in 1952 for gastrointestinal disorders, including colic in infants.[10] The INN name "dicycloverine" was recommended in 1959.[13] It was included in the combination drug for morning sickness called Bendectin, along with doxylamine and vitamin B6 which was launched in the US 1956; dicyclomine was removed from the formulation in 1976 after Merrell determined that it added no value. Bendectin became the subject of many lawsuits due to allegations that it had caused birth defects similar to thalidomide, which Merrell had also marketed in the US and Canada.[14]

    In the mid 1980s several governments restricted its use in infants due to reports of convulsions, difficult breathing, irritability, and restlessness in infants given the drug.[10]

    In 1994 the US Federal Trade Commission ordered Marion Merrell Dow, which had recently acquired Rugby Darby, the only generic manufacturer of dicycloverine in the US, to promise to grant licenses to its intellectual property on the drug to any company that wanted it, based on antitrust concerns. The US market for the drug at that time was around $8 million; Dow had 60% of it and Rugby had 40%. The next year, Hoechst Marion Roussel, which by that time had acquired the business, granted a license to Endo Pharmaceuticals. By 2000 several other generic competitors had started selling the drug. The case was part of the reshaping of the US pharmaceutical market that occurred in the 1990s, to favor generic entry.[15]

    Society and culture

    There are reports of dicycloverine abuse, but they are rare.[8]

    Cost

    In the United Kingdom the NHS pays about 1.84 £ per dose as of 2019.[2] In the United States the wholesale cost of this amount is about US$0.15.[5] In 2017, it was the 181st most commonly prescribed medication in the United States, with more than three million prescriptions.[6][7]

    • Dicyclomine costs (US)
      Dicyclomine costs (US)
    • Dicyclomine prescriptions (US)
      Dicyclomine prescriptions (US)

    References

    1. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 20 September 2020. Retrieved 7 September 2020.
    2. 1 2 3 4 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 759. ISBN 9780857113382.
    3. 1 2 3 4 5 6 7 "Dicyclomine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 5 May 2019. Retrieved 3 March 2019.
    4. ↑ "Dicyclomine Pregnancy and Breastfeeding Warnings". Drugs.com. Archived from the original on 6 March 2019. Retrieved 3 March 2019.
    5. 1 2 "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Archived from the original on 2019-03-06. Retrieved 3 March 2019.
    6. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on 12 February 2021. Retrieved 11 April 2020.
    7. 1 2 "Dicyclomine Hydrochloride - Drug Usage Statistics". ClinCalc. Archived from the original on 12 July 2020. Retrieved 11 April 2020.
    8. 1 2 3 4 5 Canadian Agency for Drugs and Technologies in Health (3 December 2015). "Dicyclomine for Gastrointestinal Conditions: A Review of the Clinical Effectiveness, Safety, and Guidelines". CADTH Rapid Response Reports. PMID 26985553. open access
    9. 1 2 3 4 AHFS Staff (2006). "Dicyclomine hydrochloride". AHFS DI Essentials. Bethesda, MD: American Society of Health-System Pharmacists / drugs.com. Archived from the original on May 5, 2019. Retrieved November 25, 2018.
    10. 1 2 3 Consolidated List of Products Whose Consumption and/or Sale Have Been Banned, Withdrawn, Severely Restricted or Not Approved by Governments (PDF) (12 ed.). World Health Organization. 2005. p. 106. Archived from the original (PDF) on January 25, 2013. Retrieved November 25, 2018.
    11. ↑ Biagioli E, Tarasco V, Lingua C, Moja L, Savino F (September 2016). "Pain-relieving agents for infantile colic". The Cochrane Database of Systematic Reviews. 9: CD009999. doi:10.1002/14651858.CD009999.pub2. hdl:2434/444531. PMC 6457752. PMID 27631535. open access
    12. ↑ "Dicyclomine". Pubchem. Archived from the original on August 20, 2018. Retrieved November 25, 2018.
    13. ↑ "International Nonproprietary Names for Pharmaceutical Preparations List #3" (PDF). WHO Chronicle. 13 (12): 463–474. December 1959. Archived (PDF) from the original on August 28, 2021. Retrieved November 25, 2018.
    14. ↑ Sanders, Joseph (January 1992). "The Bendectin Litigation: A Case Study in the Life Cycle of Mass Torts" (PDF). Hastings Law Journal. 43 (2): 317. Archived from the original on August 20, 2018. Retrieved November 25, 2018.
    15. ↑ Chien, Colleen (2003). "Cheap Drugs at What Price to Innovation: Does the Compulsory Licensing of Pharmaceuticals Hurt Innovation?". Berkeley Technology Law Journal. 18 (3): 853–907. JSTOR 24116860.
    Identifiers:
    • "Dicyclomine". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 2019-06-28. Retrieved 2019-03-11.
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