Colesevelam
| File:Colesevelam structure.svg | |
| Clinical data | |
|---|---|
| Pregnancy category |
|
| Routes of administration | Oral |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | N/A |
| Metabolism | Colesevelam is not absorbed and not metabolised. |
| Biological half-life | N/A (non-systemic drug) |
| Excretion | By intestines only, colesevelam is non-systemic. |
| Identifiers | |
| CAS Number | 182815-44-7 |
| ATC code | C10AC04 (WHO) |
| PubChem | CID 160051 |
Colesevelam is a bile acid sequestrant administered orally. It is developed by Genzyme and marketed in the US by Daiichi Sankyo under the brand name WelChol and elsewhere by Genzyme under the tradename Cholestagel.
Contents
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 as monotherapy and to improve glycemic control in adults with type 2 diabetes mellitus[1], including in combination with a statin.
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. [2]
Constituents
The compounds which constitute 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.[3]
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), a person can decrease his or her risk of developing certain health problems in the future by taking it.
In previous clinical research studies, people 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.[4]
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 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 occurred to treatment with statins alone are not unexpected frequent side effects.[5]
References
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- ↑ Colesevelam HCl Improves Glycemic Control and Reduces LDL Cholesterol in Patients With Inadequately Controlled Type 2 Diabetes on Sulfonylurea-Based Therapy
- ↑ Principles and Practice of Endocrinology and Metabolism, 2000, ed. Becker, chapter 163
- ↑ http://www.rxlist.com/welchol-drug.htm
- ↑ http://cholesterol.emedtv.com/welchol/welchol.html
- ↑ Fachinformation Cholestagel® Stand März 2009
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