Colesevelam is a bile acid sequestrant that is an FDA approved drug to be used in adjunct with diet and exercise for a variety of indications. The main indication is to lower an elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia and other diseases that cause hyperlipidemia. It can be used as a monotherapy or with an HMG-CoA reductase inhibitor (statin), ezetimibe or niacin, or in a three- or a four-drug combination. Another approved use is to reduce LDL-C levels in boys and postmenarchal girls ages 10-17 who have heterozygous familial hypercholesterolemia. For this situation, colesevelam can be used as a monotherapy or with a statin only after a proper trial of diet and exercise has failed. Finally, the last FDA approved indication is to improve glycemic control in type 2 diabetic adults.

While not an FDA approved use, colesevelam has shown to improve stool consistency in patients who have irritable bowel syndrome with diarrhea, causing an overall improvement in bowel function.[1] Overall effects were consistent with increased hepatic bile synthesis and luminal bile acid sequestration by colesevelam.[1]

Colesevelam is a novel drug created to help patients lower their LDL cholesterol levels. Its primary mechanism of action is to create nonabsorbable complexes when exposed to bile acids in the GI tract. It forms these complexes due to its numerous hydrophobic side chains, which enhances the binding of bile acids.[2] Once it forms the complexes, the bile acids are no longer able to be reabsorbed to participate in the enterohepatic bile acid recirculation system. This activity causes a reduction in the total amount of bile acids in the body, causing an upregulation of 7-alpha-hydroxylase enzyme that is responsible for converting intracellular cholesterol into bile acids. With the need for bile acids increased, hepatic LDL receptors become upregulated to provide enough cholesterol for bile acid synthesis. As more and more cholesterol diverts into creating bile acids, there is an overall decrease in the plasma LDL cholesterol level, along with a decrease in total cholesterol levels.[3] 

The main mechanism through which colesevelam reduces plasma glucose levels is not entirely understood. In animal studies, researchers have observed colesevelam to increase the levels of the hormone glucagon-like peptide-1, GLP-1, and other incretins. Mice models show that this occurs through the activation of TGR5 secondary to the binding of bile acids in the GI tract. Once GLP1 and other incretins are activated, overall hepatic glycogenolysis becomes suppressed. This suppression occurs because patients with type 2 diabetes have increased hepatic production of glucose, contributing to elevated fasting serum glucose levels. By decreasing hepatic glycogenolysis, one can expect a reduction in serum glucose levels.[2][4]

Colesevelam comes in three major forms that are available to patients. Healthcare providers have the option to chose from an oral tablet formulation, a prepared suspension, as well as a recently approved chewable bar form. The recommendation is to take either once or twice daily to achieve therapeutic effects. Also, patients with susceptibility to fat-soluble vitamin and folic acid deficiencies should take the vitamins at least 4 hours after taking colesevelam to allow for proper absorption of the vitamins. This principle also applies to statins. Statins need to be taken at least 4 hours after taking colesevelam. Patients should be counseled on proper fluid intake once started on colesevelam. 

Colesevelam comes in the following formulations:

• Chewable bar 
  • 3.75 g per bar, oral  
• Powdered suspension 
  • 3.75 g per packet, oral 
• Tablet 
  • 625 mg, oral 

Colesevelam is part of the drug class known as bile acid sequestrants. While overall, very effective and safe to use as a nonsystemic approach to lower cholesterol, tolerability, and compliance issues are not uncommon. Colesevelam has the lowest rate of side effects associated with its use, but it still shares the same side effects as the rest of the drugs in its class. Due to the mechanism of action and causing increased bile acid in the gastrointestinal tract, the predominant side effects are gastrointestinal. Symptoms like constipation, diarrhea, gas, as well as nausea, abdominal pain, and weakness, are common. Patients have also noted muscle pain to be a side effect of colesevelam.[5] Other notable side effects associated with the use of colesevelam is a significant increase in triglycerides.[6] Also, steatorrhea is a common side effect of these drugs as well. Due to this, patients should receive counsel to take this drug at least four hours before vitamin supplements, as well as statins.[7]

Colesevelam may decrease the bioavailability of many drugs including but not limited to: amiodarone, oral corticosteroids, cyclosporine (systemic), estrogen derivatives, progesterone, oral contraceptives, ezetimibe, glimepiride, glipizide, glyburide, leflunomide, lomitapide, loop diuretics like furosemide, thiazides, methotrexate, mycophenolate, nonsteroidal anti-inflammatory drugs, olmesartan, phenytoin, pravastatin, niacin, propranolol, raloxifene, tetracyclines, levothyroxine, ursodiol, oral vancomycin, warfarin and fat-soluble multivitamins A, E, D, K. If these drugs are on the treatment regimen of the patient, monitor therapy or consider therapy modification. These drugs require administration either one to two hours before or four hours after colesevelam administration (see product information of the medications mentioned above).

Colesevelam, while a generally well-tolerated drug with relatively mild side effects, does still have a few side effects that healthcare providers should know and be aware of before prescribing a patient the medication. Clinicians should not give colesevelam to patients with a history of bowel obstruction. Additionally, patients with a history of serum triglyceride concentrations greater than 500mg/dL or a history of hypertriglyceridemia-induced pancreatitis should not be given this drug due to its ability to increase triglyceride levels.[5][8]