Colesevelam, known by the brand name Welchol, is a medication known for managing cholesterol levels. It helps reduce “bad” low-density lipoprotein (LDL) cholesterol in the bloodstream, often used with diet and exercise for heart health. Beyond its primary application, colesevelam also serves an additional purpose in treating a specific type of chronic diarrhea, an off-label use.
Understanding Bile Acid Diarrhea
Bile acids play a significant role in the digestive process, beginning their journey in the liver. Synthesized from cholesterol, these acids are secreted into bile, which is then stored and concentrated in the gallbladder. Upon eating, the gallbladder releases bile into the small intestine, where bile acids act as natural detergents, breaking down dietary fats and aiding in the absorption of fat-soluble vitamins.
Normally, after assisting with fat digestion in the small intestine, approximately 95% of these bile acids are reabsorbed in the ileum, the final section of the small intestine. They then return to the liver to be recycled and reused, a process known as enterohepatic circulation. Only a small fraction, about 5%, is naturally eliminated in the feces.
Bile acid malabsorption (BAM) occurs when this reabsorption process is disrupted, allowing an excess of bile acids to spill into the colon. These unabsorbed bile acids irritate the lining of the large intestine, prompting it to secrete additional water and electrolytes. This increased fluid and accelerated muscle contractions result in the characteristic watery, urgent diarrhea associated with BAM. Common causes of BAM include surgical removal of the gallbladder (cholecystectomy), which alters bile flow, or conditions like Crohn’s disease that can damage the ileum. Certain intestinal surgeries or even radiation therapy to the abdominal-pelvic region can also contribute to the development of BAM.
Mechanism of Action in the Digestive System
Colesevelam belongs to a class of medications called bile acid sequestrants. Unlike many drugs that are absorbed into the bloodstream, colesevelam is designed to remain within the digestive tract, passing through the intestines without systemic absorption. This localized action is how it works.
The medication works by acting like a specialized sponge, forming a strong bond with excess bile acids in the intestinal lumen. This binding prevents the bile acids from being reabsorbed into the body. Once bound, the colesevelam-bile acid complex is too large to be absorbed and is instead eliminated from the body through the feces.
By removing these irritating bile acids from the colon, colesevelam reduces the excessive water secretion and accelerated bowel movements that characterize bile acid diarrhea. This process helps to firm up stool consistency and decrease the frequency and urgency of bowel movements.
Dosage and Administration Guidelines
Colesevelam is available in two primary forms for oral administration: a tablet and a powder for oral suspension. The dosage is individualized by a healthcare provider, starting at a lower amount and gradually increasing to find the most effective dose that minimizes side effects. This titration allows the body to adjust to the medication.
For tablets, they should be taken with a meal and a full glass of water or other liquid. This helps with swallowing and may aid in the medication’s action. If multiple tablets are prescribed for a single dose, they should all be taken at once. Patients who have difficulty swallowing tablets may find the powder for oral suspension a more suitable option. The powder form should be mixed with 8 ounces of water, fruit juice, or a diet soft drink and consumed immediately after mixing to ensure the full dose is taken.
Common Side Effects and Drug Interactions
While colesevelam acts locally within the gastrointestinal tract and is not absorbed into the bloodstream, most of its side effects are related to the digestive system. Common side effects can include constipation, abdominal bloating, gas, and indigestion. Some individuals may also experience nausea, vomiting, or stomach pain. While colesevelam treats diarrhea, constipation can occur as a side effect, particularly as the body adjusts to the medication.
Drug interactions are a consideration when taking colesevelam. Because colesevelam is a binding agent, it can interfere with the absorption of other medications by binding to them in the digestive tract, preventing full absorption. To minimize this risk, take other medications several hours apart from colesevelam.
Specific examples of medications that may require staggered dosing include levothyroxine, a thyroid hormone replacement, and oral contraceptives containing ethinyl estradiol and norethindrone. Metformin extended-release, used for type 2 diabetes, can also be affected, with its levels potentially increasing when coadministered. Additionally, colesevelam can reduce the absorption of fat-soluble vitamins (Vitamins A, D, E, and K), and patients taking these supplements should administer them at least four hours prior to colesevelam. Informing a doctor about all other medications, vitamins, and supplements being taken is important to manage potential interactions.