Intervention and alternatives

Intervention and alternatives

Colesevelam is a bile acid sequestrant that forms a polymeric gel in the gastrointestinal tract. It binds bile acids in the small bowel and prevents the secretory action of bile acids on the colon.

Colesevelam (Cholestagel, Sanofi) is licensed by the European Medicines Agency to reduce levels of total cholesterol and low-density lipoprotein cholesterol in people with primary hypercholesterolaemia. Colesevelam can be prescribed in combination with statins and/or ezetimibe, or as monotherapy if statins are inappropriate or not tolerated.

Colesevelam is not licensed to treat bile acid malabsorption; therefore, the use of colesevelam for this indication is off-label.


Bile acid malabsorption is one of several causes of chronic diarrhoea. Estimates of the prevalence of chronic diarrhoea in western populations are between 4% and 5%. Chronic diarrhoea is one of the most common reasons for referral to a gastrointestinal clinic and can account for as many as 1 in 20 referrals.

Bile acids are synthesised in the liver from cholesterol before being transferred in conjugated form to the bile ducts and stored in the gall bladder. After a meal, the gall bladder contracts and bile acids flow into the intestinal lumen to emulsify dietary fats. Most of the bile acids (97%) are then reabsorbed and returned to the liver.

In people with bile acid malabsorption, excess bile in the colon stimulates electrolyte and water secretion, which results in chronic watery diarrhoea. Bile acid malabsorption causes diarrhoea by 1 or more of the following mechanisms:

  • inducing secretion of sodium and water

  • increasing colonic motility

  • stimulating defecation

  • inducing mucus secretion

  • damaging the mucosa, thereby increasing mucosal permeability.

Bile acid malabsorption has been divided into 3 types depending on aetiology:

  • type 1: following ileal resection, disease or bypass of the terminal ileum

  • type 2: primary idiopathic malabsorption

  • type 3: associated with cholecystectomy, peptic ulcer surgery, chronic pancreatitis, coeliac disease or diabetes mellitus.

Although not life threatening, bile acid malabsorption can have a considerable impact on lifestyle and quality of life because the associated increased frequency of bowel motions may limit the person's ability to travel or leave the house.

Alternative treatment options

After a definitive diagnosis of bile acid malabsorption, people can be treated with bile acid sequestrants that bind with bile acids in the small bowel and prevent the secretory action of bile acids on the colon. There are currently 3 bile acid sequestrants available: colestyramine, colestipol and colesevelam.

Colestyramine and colestipol are anion exchange resins that have a high affinity for bile acids in the gastrointestinal tract, and form complexes with them. An important disadvantage of colestyramine and colestipol is that they are powders that require mixing with water or another liquid and may have an unpleasant taste, which can lead to poor tolerance of and adherence to treatment. Adverse effects include constipation, nausea, borborygmi, flatulence, bloating and abdominal pain. Colesevelam binds to bile acids with higher affinity than colestyramine or colestipol. It is available in tablet form.

The summary of product characteristic for Questran states that colestyramine is licensed for the relief of diarrhoea associated with ileal resection, Crohn's disease, vagotomy and diabetic vagal neuropathy, and to control radiation-induced diarrhoea. It is also licensed for hypercholesterolemia and the primary prevention of coronary heart disease, and for the relief of pruritus associated with partial biliary obstruction and primary biliary cirrhosis.

Colestipol is not licensed for treating bile acid malabsorption. The summary of product characteristics for Colestid states that it is licensed for treating hypercholesterolaemia, alone or in combination with additional lipid-lowering agents.