Colesevelam is a

bile acid sequestrant The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption f ...

administered orally. It was developed by GelTex Pharmaceuticals and later acquired by Genzyme. It is marketed in the US by

Daiichi Sankyo is a global pharmaceutical company and the second-largest pharmaceutical company in Japan. It achieved JPY 1,278 billion in revenue in 2022. The company owns the American pharmaceutical company American Regent. Daiichi Sankyo, Inc. (DSI) began ...

under the brand name Welchol and elsewhere by Genzyme as Cholestagel. In Canada, it is marketed by

Valeant Bausch Health Companies Inc. is a global, diversified American-Canadian pharmaceutical company. Its global corporate headquarters are located in Laval, Quebec, Canada, and its U.S. headquarters are in Bridgewater, New Jersey. It develops, manufa ...

as Lodalis.

Clinical use

Colesevelam is indicated as an adjunct to diet and exercise to reduce elevated

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density ...

cholesterol (LDL-C) in patients with primary

hyperlipidemia Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...

as monotherapy and to improve glycemic control in adults with type 2

diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

, including in combination with a

statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

. The expanded use of colesevelam in adults with type 2 diabetes mellitus is an example of

drug repositioning Drug repositioning (also called drug repurposing) involves the investigation of existing drugs for new therapeutic purposes. Repurposing achievements Repurposing generics can have groundbreaking effects for patients: 35% of 'transformative' ...

. Colesevelam is one of the bile-acid sequestrants, which along with

niacin Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Nicotinic acid is also a prescription medication. Amounts f ...

and the statins, are the three main types of cholesterol-lowering agents. The statins are considered the first-line agents. This is because of the larger body of evidence supporting statins' ability to prevent cardiovascular disease, as well as the prominent side effects from the other two types, including bloating and constipation (bile-acid sequestrants) and skin flushing (niacin). These side effects often lead to low patient compliance. Colesevelam can be used instead of

cholestyramine Colestyramine ( INN) or cholestyramine ( USAN) (trade names Questran, Questran Light, Cholybar, Olestyr, Quantalan, Vasosan) is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong i ...

in symptomatic chronic

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

due to

bile salt malabsorption Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt di ...

(

bile acid diarrhea Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt di ...

), which can be a primary condition, or secondary to

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

or the

postcholecystectomy syndrome Postcholecystectomy syndrome (PCS) describes the presence of abdominal symptoms after a cholecystectomy (gallbladder removal). Symptoms occur in about 5 to 40 percent of patients who undergo cholecystectomy, and can be transient, persistent or li ...

Constituents

Colesevelam is a modified polyallylamine. It is made by crosslinking polyallylamine with epichlorohydrin, and then modifying it with and (6-bromohexyl)trimethylammonium bromide. The bromide ions are then replaced with chloride ions when the material is washed. The constituents of the polymer colesevelam shown as subunits that do not exist per se in the final product are: ''N-prop-2-enyldecan-1-amine; trimethyl- -(prop-2-enylamino)hexylzanium; prop-2-en-1-amine; 2-(chloromethyl)oxirane; hydrogen chloride; chloride.''

Mechanism of action

Colesevelam is part of a class of drugs known as bile acid sequestrants. Colesevelam hydrochloride, the active pharmaceutical ingredient in Welchol, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 7-α-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids. This causes an increased demand for cholesterol in the liver cells, resulting in the dual effect of increasing transcription and activity of the cholesterol biosynthetic enzyme, HMG-CoA reductase, and increasing the number of hepatic LDL receptors. These compensatory effects result in increased clearance of LDL-C from the blood, resulting in decreased serum LDL-C levels. Serum TG levels may increase or remain unchanged.

Side effects

In controlled clinical studies involving approximately 1,400 patients, the following adverse reactions have been reported in patients treated with colesevelam. When reporting to the very common (≥ 1 / 10), common (≥ 1 / 100, 51/10), uncommon (≥ 1 / 1000, 51/100), rare (≥ 1/10.000, 51/1000) and distinction very rarely (51/10.000), including individual cases: * Investigations Common: serum triglyceride increased; Uncommon: serum transaminase increases * Nervous system disorders Common: headache * Gastrointestinal disorders Very Common: flatulence, constipation; Common: vomiting, diarrhea, dyspepsia, abdominal pain, stool abnormalities, nausea * Musculoskeletal and connective tissue disorders Uncommon: myalgia The background incidence of flatulence and diarrhea was the same in patients in controlled clinical trials, and higher in the placebo group. Only constipation and dyspepsia were shown to occur in a higher percentage of patients who received Cholestagel, compared to the placebo group. Side effects were generally mild or moderate in severity. In the application of colesevelam in combination with statins, no unexpected frequent side effects occurred.

References

{{Authority control Hepatology Bile acid sequestrants Daiichi Sankyo