Colesevelam
Encyclopedia
Colesevelam is a bile acid sequestrant
Bile acid sequestrant
The bile acid sequestrants are a group of medications used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic...

 administered orally. It is developed by Genzyme
Genzyme
Genzyme Corporation is a fully owned subsidiary of Sanofi-Aventis. Before its acquisition, Genzyme was an American biotechnology company based in Cambridge, Massachusetts. In 2010, Genzyme was the world’s third-largest biotechnology company, employing more than 11,000 people around the world...

 and marketed in the US by Daiichi Sankyo under the brand name WelChol and elsewhere by Genzyme under the tradename Cholestagel.

Clinical use

Colesevelam is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia
Hyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...

 as monotherapy and to improve glycemic control in adults with type 2 diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

, including in combination with a statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...

. The expanded use of colesevelam in adults with type 2 diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

 is an example of drug repositioning
Drug repositioning
Drug repositioning is the application of known drugs and compounds to new indications .- Drug repositioning :...

.

Colesevelam is one of the bile-acid sequestrants, which along with niacin and the statins are the three main types of cholesterol-lowering agents. The statins are considered the first-line agents. This is because of 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.

Constituents

The constituents of the polymer colesevelam are:



N-prop-2-enyldecan-1-amine; trimethyl-[6-(prop-2-enylamino)hexyl]azanium; prop-2-en-1-amine; 2-(chloromethyl)oxirane; hydrogen chloride; chloride.

How it works

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 decreasing 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.

It is not yet known how Colesevelam works to help control blood sugar in people with type 2 diabetes. However, it is clear that the drug works within the digestive tract, since it is not absorbed into the rest of the body.

Cholesterol

Since Colesevelam can lower total and LDL cholesterol levels (along with raising HDL - "good" cholesterol), taking it may decrease one's risk of developing certain health problems in the future.

Previous clinical research studies indicate individuals taking 3,800 mg to 4,500 mg of Colesevelam daily were able to:
  • Reduce LDL cholesterol by 15 to 18 percent.
  • Reduce total cholesterol by 7 to 10 percent.
  • Raise HDL cholesterol by 3 percent.


The combination of Colesevelam with a HMG-CoA reductase inhibitor (known more commonly as a statin) can further lower cholesterol levels.

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 in patients in the same controlled clinical trials, the placebo were higher. Only constipation and dyspepsia were shown to occur in a higher percentage of patients who received Cholestagel, compared to the placebo reported. Side effects were generally mild or moderate in severity. In the application of colesevelam in combination with statins, no unexpected frequent side effects occurred.

External links

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