Macrogol

Macrogol
Names
Trade namesMiraLax, ClearLax, Golytely, others
Other namesPolyethylene glycol (PEG), PEG 3350, PEG 4000, PEG 6000
IUPAC name
  • Poly(oxyethylene)
Clinical data
Drug classOsmotic laxative
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1
    Routes of
    use    		By mouth
    Defined daily dose10 grams[1]
    External links
    AHFS/Drugs.comProfessional Drug Facts
    MedlinePlusa603032
    Legal
    License data
    Legal status
    Pharmacokinetics
    BioavailabilityNone
    ExcretionFaeces (100%)
    Chemical and physical data
    FormulaH–(OCH2CH2)n–OH
    Molar massVaries

    Macrogol, also known as polyethylene glycol (PEG), is used as a medication to treat constipation in children and adults.[2] It is also used to empty the bowels before a colonoscopy.[2] It is taken by mouth.[2] Benefits usually occur within three days.[3] Generally it is only recommended for up to two weeks.[4]

    Side effects may include increased bowel gas, abdominal pain, and nausea.[2] Rare but serious side effects may include an abnormal heartbeat, seizures, and kidney problems.[5] Use appears to be safe during pregnancy.[6][2] It is classified as an osmotic laxative.[3] It works by increasing the amount of water in the stool.[4]

    Macrogol came into use as a bowel prep in 1980 and was approved for medical use in the United States in 1999.[7][8][9] It is available as a generic medication and over the counter.[2][10] In the United Kingdom it costs the NHS about £0.14 per dose as of 2019.[2] In the United States the wholesale cost of this amount is about US$1.40.[11] In 2017, it was the 162nd most commonly prescribed medication in the United States, with more than three million prescriptions.[12][13] Typically it is formulated together with electrolytes.[14]

    Medical uses

    Constipation

    Macrogol 4000, pharmaceutical quality

    Macrogol 3350, often in combination with electrolytes, is used for short-term relief of constipation as well as for long-term use in constipation of various causes, including in multiple sclerosis and Parkinson as well as constipation caused by medications such as opioids and anticholinergics. Whole bowel irrigation with macrogol is part of the bowel preparation before surgery or colonoscopy. Limited data also support its use for the treatment of fecal impaction.[15]

    It is at least as, if not more, effective than other agents.[16] In those with chronic constipation it works better than lactulose.[17] There is a better response than to tegaserod.[18]

    Popular types include: macrogol 3350,[19] macrogol 4000, and macrogol 6000.[20] The number represents the average molecular mass. Combining different molecular masses provides some control over the consistency.[21]

    Excipient

    Macrogol is used as an excipient in many pharmaceutical products. Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as ointment bases, tablet binders, film coatings, and lubricants.[21] It is also used in lubricating eye drops.

    PEGylation

    Macrogols are also attached to biopharmaceutical drugs to slow down their degradation in the human body and increase their duration of action, as well as to reduce immunogenicity. This process is called PEGylation.[22][23]

    Dosage

    The defined daily dose is 10 grams by mouth.[1] It is commonly used as 120 to 240 ml by mouth twice a day as needed. The 17 grams of powder (one rounded table spoon) can be mixed in 120 to 240 ml.[24]

    Contraindications

    Contraindications for macrogol taken orally as a laxative are intestinal perforation, bowel obstruction, ileus, inflammatory bowel diseases, and toxic megacolon.[15]

    The doses of macrogol as an excipient are too low to have relevant contraindications.[25]

    Allergy to macrogol is rare, and usually appears as an allergy to an increasing number of seemingly unrelated products, including cosmetics, drugs that use it as an excipient, and peri-procedural substances such as ultrasound gel.[26]

    Side effects

    Macrogol by mouth is generally well tolerated. Possible side effects include headache, bloating, nausea, allergies, and electrolyte imbalance, mainly hypokalaemia (low blood potassium levels) and hyperkalaemia (high blood potassium levels). Hyperkalaemia is not an effect of macrogol itself but of potassium salts which are usually part of macrogol formulations.[15] With excessive use, it can cause diarrhea.

    Interactions

    The interaction potential is low. Resorption of other pharmaceutical drugs can be reduced because oral macrogol accelerates intestinal passage, but this is seldom clinically relevant. For antiepileptic drugs, such a mechanism has been described in rare cases.[15]

    Pharmacology

    Macrogol is an osmotically acting laxative, that is an inert substance that passes through the gut without being absorbed into the body. It relieves constipation because it causes water to be retained in the bowel instead of being absorbed into the body. This increases the water content and volume of the stools in the bowel, making them softer and easier to pass, as well as improving gut motility.[15][27][28]

    Chemistry

    Society and culture

    Cost

    In the United Kingdom it costs the NHS about £0.14 per dose as of 2019.[2]In the United States the wholesale cost of this amount is about US$1.40.[11]In 2017, it was the 162nd most commonly prescribed medication in the United States, with more than three million prescriptions.[12][13]

    • Polyethylene glycol 3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride, and potassium chloride costs (US)
      Polyethylene glycol 3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride, and potassium chloride costs (US)
    • Polyethylene glycol 3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride, and potassium chloride (US)
      Polyethylene glycol 3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride, and potassium chloride (US)

    Available forms

    Macrogol is sold as a non-prescription preparation in the form of powder. When sold for gut cleansing (and as a laxative), it is usually in combination with salts such as sodium bicarbonate, sodium chloride and potassium chloride[29] to help mitigate the possibility of electrolyte imbalance and dehydration. Trade names include SoftLax, Purelax, MiraLax, Laxido, Glycoprep, Movicol, Cololyt and Osmolax, and many others.

    It is dissolved in water to create a clear and odorless solution which is then drunk. While most consumers find the taste of macrogol itself to be very mild and unobjectionable, the electrolytes contained in formulations for purging and cleansing give the solution an extremely salty and bitter taste.

    Polyethylene glycol-electrolyte solution is a prescription product sold under various brand names including Colyte, Gavilyte, Golytely, Nulytely, Moviprep, and Trilyte.[30]

    Research

    PEGylation
    The protein uricase can be PEGylated to form pegloticase, which improves its solubility at physiological pH, increases serum half-life and reduces immunogenicity without compromising activity. Upper images show the whole tetramer, lower images show one of the lysines that is PEGylated. (PDB: 1uox​ PEG-uricase model from reference[31])
    Main article: PEGylation

    When attached to various biopharmaceutical medications (which are proteins), macrogol results in a slowed clearance of the carried protein from the blood. This makes for a longer-acting medicinal effect and reduces toxicity, and it allows for longer dosing intervals. It also reduces the proteins' immunogenicity. Examples for PEGylated proteins include peginterferon alfa-2a and -2b, which are used to treat hepatitis C, pegfilgrastim, which is used to treat neutropenia, and pegloticase for the treatment of gout.[15]

    Nerves and spinal cords
    • It has been shown that macrogol can improve healing of spinal injuries in dogs.[32]
    • One of the earlier findings is that macrogol can aid in nerve repair.[33]
    • The subcutaneous injection of macrogol 2000 in guinea pigs after spinal cord injury leads to rapid recovery through molecular repair of nerve membranes.[34] The effectiveness of this treatment to prevent paraplegia in humans after an accident is not known yet.
    • Macrogol is being used in the repair of motor neurons damaged in crush or laceration incidents in vivo and in vitro. When coupled with melatonin, 75% of damaged sciatic nerves were rendered viable.[35]
    Cancer prevention
    • High-molecular-weight macrogol (e.g., 8000 g/mol) has been shown to be a dietary preventive agent against colorectal cancer in animal models.[36]
    • The Chemoprevention Database shows macrogol is the most effective known agent for the suppression of chemical carcinogenesis in rats. Cancer prevention applications in humans, however, have not yet been tested in clinical trials.[37]
    Other

    References

    1. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 10 April 2021. Retrieved 9 September 2020.
    2. 1 2 3 4 5 6 7 8 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 57–58. ISBN 9780857113382.
    3. 1 2 "DailyMed - polyethylene glycol 3350 powder, for solution". dailymed.nlm.nih.gov. Archived from the original on 26 April 2021. Retrieved 19 April 2019.
    4. 1 2 "Polyethylene Glycol 3350: MedlinePlus Drug Information". medlineplus.gov. Archived from the original on 27 April 2021. Retrieved 19 April 2019.
    5. ↑ "PEG-3350 and Electrolytes for Oral Solution" (PDF). FDA. Archived (PDF) from the original on 30 August 2017. Retrieved 19 April 2019.
    6. ↑ "Polyethylene glycol 3350 Use During Pregnancy". Drugs.com. Archived from the original on 28 April 2021. Retrieved 19 April 2019.
    7. ↑ Townsend, Courtney M.; Beauchamp, R. Daniel; Evers, B. Mark; Mattox, Kenneth L. (2016). Sabiston Textbook of Surgery E-Book: The Biological Basis of Modern Surgical Practice. Elsevier Health Sciences. p. 1325. ISBN 9780323401630. Archived from the original on 2021-04-30. Retrieved 2020-05-22.
    8. ↑ "Prescription Polyethylene Glycol 3350; Denial of a Hearing and Order Withdrawing Approval of Abbreviated New Drug Applications". Federal Register. 2 April 2018. Archived from the original on 28 April 2021. Retrieved 19 April 2019.
    9. ↑ Ginsberg, Gregory G.; Kochman, Michael L.; Norton, Ian D.; Gostout, Christopher J. (2011). Clinical Gastrointestinal Endoscopy E-Book: Expert Consult - Online and Print. Elsevier Health Sciences. p. 87. ISBN 9781437735703. Archived from the original on 2021-04-30. Retrieved 2020-05-22.
    10. ↑ "Polyethylene glycol 3350 Uses, Side Effects & Warnings". Drugs.com. Archived from the original on 28 April 2021. Retrieved 19 April 2019.
    11. 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.
    12. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on 12 February 2021. Retrieved 11 April 2020.
    13. 1 2 "Polyethylene Glycol 3350 - Drug Usage Statistics". ClinCalc. Archived from the original on 3 March 2021. Retrieved 11 April 2020.
    14. ↑ Aronson, Jeffrey K. (2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. p. 567. ISBN 9780444537164. Archived from the original on 2021-04-30. Retrieved 2020-05-22.
    15. 1 2 3 4 5 6 Haberfeld, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.{{cite book}}: CS1 maint: unrecognized language (link)
    16. ↑ Ton, Joey (4 April 2011). "#45 Polyethylene Glycol (PEG) for Paediatric and Adult Chronic Constipation". CFPCLearn. Archived from the original on 25 March 2023. Retrieved 18 June 2023.
    17. ↑ Lee-Robichaud, H; Thomas, K; Morgan, J; Nelson, RL (7 July 2010). "Lactulose versus Polyethylene Glycol for Chronic Constipation". The Cochrane Database of Systematic Reviews (7): CD007570. doi:10.1002/14651858.CD007570.pub2. PMID 20614462.
    18. ↑ Di Palma, Jack A.; Cleveland, Mark vB.; McGowan, John; Herrera, Jorge L. (2007). "A Randomized, Multicenter Comparison of Polyethylene Glycol Laxative and Tegaserod in Treatment of Patients With Chronic Constipation". The American Journal of Gastroenterology. 102 (9): 1964–71. PMID 17573794.
    19. ↑ Hardikar W, Cranswick N, Heine RG (2007). "Macrogol 3350 plus electrolytes for chronic constipation in children: a single-centre, open-label study". Journal of Paediatrics and Child Health. 43 (7–8): 527–31. doi:10.1111/j.1440-1754.2007.01116.x. PMID 17635680.
    20. ↑ Hyry H, Vuorio A, Varjonen E, Skyttä J, Mäkinen-Kiljunen S (2006). "Two cases of anaphylaxis to macrogol 6000 after ingestion of drug tablets". Allergy. 61 (8): 1021. doi:10.1111/j.1398-9995.2006.01083.x. PMID 16867059.
    21. 1 2 Smolinske, Susan C. (1992). Handbook of Food, Drug, and Cosmetic Excipients. p. 287. ISBN 9780849335853.
    22. ↑ Veronese, FM; Harris, JM (2002). "Introduction and overview of peptide and protein pegylation". Advanced Drug Delivery Reviews. 54 (4): 453–6. doi:10.1016/S0169-409X(02)00020-0. PMID 12052707.
    23. ↑ "Things About PEGylation Technology and Biopharmaceuticals You Should Know". Biochempeg. Archived from the original on 2020-06-06. Retrieved 2020-01-10.
    24. ↑ "AboutKidsHealth". www.aboutkidshealth.ca. Archived from the original on 18 March 2021. Retrieved 22 March 2021.
    25. ↑ "Compound Macrogol Oral Powder Sugar Free. - Summary of Product Characteristics (SmPC) - (emc)". www.medicines.org.uk. Archived from the original on 2021-08-28. Retrieved 2020-01-10.
    26. ↑ Wenande, E.; Garvey, L. H. (2016-07-01). "Immediate-type hypersensitivity to polyethylene glycols: a review". Clinical & Experimental Allergy. 46 (7): 907–922. doi:10.1111/cea.12760. ISSN 1365-2222. PMID 27196817.
    27. ↑ Mutschler, Ernst (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 608. ISBN 978-3-8047-2898-1.{{cite book}}: CS1 maint: unrecognized language (link)
    28. ↑ Chaussade, S (1999). "Mechanisms of action of low doses of polyethylene glycol in the treatment of functional constipation". Italian Journal of Gastroenterology and Hepatology. 31 Suppl 3: S242–4. PMID 10726227.
    29. ↑ [eg. Laxido package insert]
    30. ↑ "Polyethylene Glycol-Electrolyte Solution (Professional Patient Advice)". Drugs.com. 20 February 2020. Archived from the original on 8 June 2020. Retrieved 8 June 2020.
    31. ↑ Sherman, MR; Saifer, MG; Perez-Ruiz, F (3 January 2008). "PEG-uricase in the management of treatment-resistant gout and hyperuricemia". Advanced Drug Delivery Reviews. 60 (1): 59–68. doi:10.1016/j.addr.2007.06.011. PMID 17826865.
    32. ↑ Bowman, Lee (4 December 2004). "Study on dogs yields hope in human paralysis treatment". seattlepi.com. Archived from the original on 22 September 2021. Retrieved 26 June 2016.
    33. ↑ Krause, T. L.; Bittner, G. D. (1990). "Rapid morphological fusion of severed myelinated axons by polyethylene glycol". PNAS. 87 (4): 1471–1475. Bibcode:1990PNAS...87.1471K. doi:10.1073/pnas.87.4.1471. PMC 53497. PMID 2304913.
    34. ↑ Borgens, R. B.; Bohnert, D (2001). "Rapid recovery from spinal cord injury after subcutaneously administered polyethylene glycol". Journal of Neuroscience Research. 66 (6): 1179–1186. doi:10.1002/jnr.1254. PMID 11746451.
    35. ↑ Stavisky, R. C.; Britt, J. M.; Zuzek, A; Truong, E; Bittner, G. D. (2005). "Melatonin enhances the in vitro and in vivo repair of severed rat sciatic axons". Neuroscience Letters. 376 (2): 98–101. doi:10.1016/j.neulet.2004.11.033. PMID 15698928.
    36. ↑ Corpet, D. E.; Parnaud, G; Delverdier, M; Peiffer, G; Taché, S (2000). "Consistent and Fast Inhibition of Colon Carcinogenesis by Polyethylene Glycol in Mice and Rats Given Various Carcinogens". Cancer Research. 60 (12): 3160–3164. PMID 10866305.
    37. ↑ Chemoprevention Database Archived 2005-11-23 at the Wayback Machine. Inra.fr. Retrieved on 30 November 2012.
    38. ↑ Lo, M. M.; Tsong, T. Y.; Conrad, M. K.; Strittmatter, S. M.; Hester, L. D.; Snyder, S. H. (1984). "Monoclonal antibody production by receptor-mediated electrically induced cell fusion". Nature. 310 (5980): 792–4. Bibcode:1984Natur.310..792L. doi:10.1038/310792a0. PMID 6088990.
    Identifiers:
    • "Macrogol". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 2020-06-08. Retrieved 2020-06-08.
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