Macrogol, also known as

polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular we ...

(PEG), is used as a medication to treat

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel moveme ...

in children and adults. It is also used to empty the

bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

s before a

colonoscopy Colonoscopy () or coloscopy () is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It can provide a visual diagnosis ('' ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Benefits usually occur within three days. Generally it is only recommended for up to two weeks. It is also used as an

excipient An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...

. Side effects may include increased bowel gas, abdominal pain, and nausea. Rare but serious side effects may include an abnormal heartbeat,

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

s, and

kidney problems Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. Use appears to be safe during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

. It is classified as an

osmotic laxative Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubr ...

. It works by increasing the amount of water in the stool. Macrogol came into use as a bowel prep in 1980 and was approved for medical use in the United States in 1999. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

and

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

. In 2020, it was the 226th most commonly prescribed medication in the United States, with more than 2million prescriptions. Typically it is formulated together with

electrolytes An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon di ...

Medical uses

Constipation

Macrogol 3350, often in combination with

electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon ...

s, is used for short-term relief of constipation as well as for long-term use in constipation of various causes, including in

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...

and

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

patients (an often-overlooked non-motor symptom) as well as constipation caused by pharmaceutical drugs such as

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

s and

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

s. Whole bowel irrigation with macrogol is part of the bowel preparation before

surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...

. Limited data also support its use for the treatment of

fecal impaction A fecal impaction is a solid, immobile bulk of feces that can develop in the rectum as a result of chronic constipation. A related term is fecal loading which refers to a large volume of stool in the rectum of any consistency. Fecal impaction is ...

. In those with chronic constipation it works better than

lactulose Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy. It is used by mouth for constipation and either by mouth or in the rectum for hepatic encephalopathy. It generally begins working after 8–12 ...

. A 2007 comparison showed that people with constipation had a better response to macrogol than to

tegaserod Tegaserod is a 5-HT4 agonist manufactured by Novartis and sold under the names Zelnorm and Zelmac for the management of irritable bowel syndrome and constipation. Approved by the FDA in 2002, it was subsequently removed from the market in 2007 du ...

. Popular types include: macrogol 3350, macrogol 4000, and macrogol 6000. The number represents the average

molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quant ...

. Combining different molecular masses provides some control over the consistency.

Excipient

Macrogol is used as an

in pharmaceutical products. Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as

ointment A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

bases,

tablet Tablet may refer to: Medicine * Tablet (pharmacy), a mixture of pharmacological substances pressed into a small cake or bar, colloquially called a "pill" Computing * Tablet computer, a mobile computer that is primarily operated by touching the ...

binders,

film coating A film coating is a thin polymer-based coat that is typically sprayed on to a solid pharmaceutical dosage form, such as a tablet, capsule, pellet or granule. Film coating can impact both its appearance and its pharmacokinetics making it an essen ...

s, and

lubricant A lubricant (sometimes shortened to lube) is a substance that helps to reduce friction between surfaces in mutual contact, which ultimately reduces the heat generated when the surfaces move. It may also have the function of transmitting forces, t ...

s. For example, PEG-2000 is one of the excipients in the

Moderna COVID-19 vaccine The Moderna COVID19 vaccine ( INN: elasomeran), sold under the brand name Spikevax, is a COVID-19 vaccine developed by American company Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID), and the Biomed ...

PEGylation

Macrogols are also attached to

biopharmaceutical drug A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, th ...

s to slow down their degradation in the human body and increase their duration of action, as well as to reduce

immunogenicity Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...

. This process is called

PEGylation PEGylation (or pegylation) is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol (PEG, in pharmacy called macrogol) polymer chains to molecules and macrostructures, such as a drug, therapeutic protein ...

Contraindications

Contraindications for macrogol taken orally as a laxative are

intestinal perforation Gastrointestinal perforation, also known as ruptured bowel, is a hole in the wall of part of the gastrointestinal tract. The gastrointestinal tract includes the esophagus, stomach, small intestine, and large intestine. Symptoms include severe abd ...

bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs ...

ileus Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction. The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' ref ...

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well ...

s, and toxic megacolon. The doses of macrogol as an

are too low to have relevant contraindications.

Allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

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.

Adverse effects

Oral macrogol is generally well tolerated. Possible side effects include headache, bloating, nausea,

allergies Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermat ...

, and

electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...

, mainly

hypokalaemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnorm ...

(low blood

potassium Potassium is the chemical element with the symbol K (from Neo-Latin '' kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmos ...

levels) and

hyperkalaemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occas ...

(high blood potassium levels). Hyperkalaemia is not an effect of macrogol itself but of potassium salts which are usually part of macrogol formulations. With excessive use, it can cause diarrhea.

Interactions

The interaction potential is low. Absorption of other pharmaceutical drugs can be reduced because oral macrogol accelerates intestinal passage, but this is seldom clinically relevant. For

antiepileptic drug Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

s, such a mechanism has been described in rare cases.

Pharmacology

Mechanism of action as a laxative

Macrogol is an osmotically acting laxative; that is, an inert substance that passes through the gut without being absorbed into the body. It relieves

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 Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whic ...

Chemistry

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 bicarbonate ( IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation ( Na+) and a bicarbonate anion ( HCO3− ...

sodium chloride Sodium chloride , commonly known as salt (although sea salt also contains other chemical salts), is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. With molar masses of 22.99 and 35. ...

and

potassium chloride Potassium chloride (KCl, or potassium salt) is a metal halide salt composed of potassium and chlorine. It is odorless and has a white or colorless vitreous crystal appearance. The solid dissolves readily in water, and its solutions have a salt ...

to help mitigate the possibility of electrolyte imbalance and

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

. Brand names include SoftLax, Purelax, MiraLax, Laxido, Glycoprep, CosmoCol, Movicol, Cololyt, Osmolax, and 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.

Research

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 Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...

, 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 Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...

pegfilgrastim Pegfilgrastim, sold under the brand name Neulasta among others, is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (GCSF) analog filgrastim. It serves to stimulate the production of white blood cells (neutrophils) ...

, which is used to treat

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteri ...

, and

pegloticase Pegloticase (trade name Krystexxa) is a medication for the treatment of severe, treatment-refractory, chronic gout. It is a third line treatment in those in whom other treatments are not tolerated. The drug is administered by infusion intravenously ...

for the treatment of

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...

Nerves and spinal cords

There is evidence demonstrating PEG-induced repair of specific nerve cells in animal models: * It has been shown that macrogol can improve healing of spinal injuries in dogs. * One of the earlier findings is that macrogol can aid in nerve repair in

earthworms An earthworm is a terrestrial invertebrate that belongs to the phylum Annelida. They exhibit a tube-within-a-tube body plan; they are externally segmented with corresponding internal segmentation; and they usually have setae on all segments. T ...

. * The subcutaneous injection of macrogol 2000 in guinea pigs after spinal cord injury leads to rapid recovery through molecular repair of nerve membranes. The effectiveness of this treatment to prevent

paraplegia Paraplegia, or paraparesis, is an impairment in motor or sensory function of the lower extremities. The word comes from Ionic Greek () "half-stricken". It is usually caused by spinal cord injury or a congenital condition that affects the neur ...

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 Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...

'' and ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

''. When coupled with melatonin, 75% of damaged sciatic nerves were rendered viable.

Cancer prevention

* High-molecular-weight macrogol (e.g., 8000 g/mol) has been shown to be a dietary preventive agent against

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...

in animal models. * 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 trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

Other

* Macrogol is also used to fuse B-cells with myeloma cells in

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

production.

References

External links

* {{Portal bar , Medicine Wikipedia medicine articles ready to translate Laxatives Excipients Merck & Co. brands Bayer brands