Colesevelam is a medication primarily recognized for managing high cholesterol levels, but it also treats a specific type of chronic diarrhea. It belongs to the class of bile acid sequestrants, which reduce low-density lipoprotein (LDL) cholesterol. Healthcare providers frequently utilize it off-label due to its effectiveness against chronic, watery diarrhea that does not respond to standard treatments. This action targets the root cause of certain digestive issues, offering significant relief where other medications fail.
How Colesevelam Stops Diarrhea
The effectiveness of colesevelam in controlling diarrhea is linked to its function as a bile acid sequestrant. Bile acids are compounds made by the liver and stored in the gallbladder, released into the small intestine to aid in fat digestion. Normally, about 95% of these bile acids are reabsorbed in the terminal ileum and returned to the liver for reuse in a process called enterohepatic circulation.
When this reabsorption is impaired, excess bile acids escape into the large intestine (colon). These excess bile acids irritate the colon lining, triggering two main responses. First, they stimulate colon cells to secrete large volumes of water and electrolytes, increasing the liquid content of the stool. Second, they increase colonic motility, causing the muscles to contract more frequently and forcefully.
Colesevelam works by binding directly to these bile acids in the intestinal tract, forming a large, insoluble complex. Since this complex cannot be absorbed, it is safely eliminated in the stool. By sequestering the excess bile acids, the medication prevents them from reaching the colon where they cause irritation and fluid secretion. This action reduces the osmotic effect and hypermotility, resulting in the formation of more solid and less frequent stools.
Identifying Diarrhea Caused by Bile Acid Malabsorption
Colesevelam is indicated for diarrhea caused by Bile Acid Malabsorption (BAM), sometimes referred to as Bile Acid Diarrhea (BAD). BAM occurs when the small intestine fails to reabsorb bile acids efficiently, allowing them to spill into the large intestine. Patients commonly experience chronic, watery diarrhea that is often urgent and may be yellow or foul-smelling due to unabsorbed bile acids and fats.
BAM is categorized into three types based on its underlying cause. Type 1 BAM is secondary to diseases or surgeries that damage the ileum, such as Crohn’s disease or the surgical removal of part of the ileum (ileal resection). This physical damage prevents the bile acids from being properly absorbed.
Type 2 BAM is primary or idiopathic, meaning it occurs without any obvious underlying disease or structural problem in the gut. The mechanism in this type is often related to the liver overproducing bile acids due to a disruption in the feedback loop that regulates their synthesis. Type 3 BAM is associated with other gastrointestinal conditions, including Celiac disease, chronic pancreatitis, or post-cholecystectomy syndrome (diarrhea after gallbladder removal).
Diagnosing BAM is important because the condition often mimics other disorders like Irritable Bowel Syndrome with Diarrhea (IBS-D), leading to incorrect treatment. The effectiveness of colesevelam in rapidly resolving chronic diarrhea can serve as a strong diagnostic indicator of BAM. By targeting the specific mechanism of excess bile acids in the colon, the medication addresses the precise cause of the diarrhea.
Dosage Administration and Potential Side Effects
Colesevelam is administered in tablet form, and the dosage for treating diarrhea varies based on the patient’s needs and response, often ranging between 1.25 grams and 3.75 grams per day. This typically translates to two to six 625 mg tablets daily. It is recommended to take the medication with meals to maximize its effectiveness in binding bile acids as they are released during digestion.
A healthcare provider usually advises a gradual increase in dose, starting low and slowly building up to the required amount over several days or weeks. This strategy helps the digestive system adjust to the medication and minimizes potential gastrointestinal discomfort. The total daily dosage is often split and taken with two of the largest meals of the day for consistent symptom control.
The most common side effects are localized to the gastrointestinal tract, which is expected given its mechanism of action. The most frequent adverse effects reported are constipation, bloating, abdominal discomfort, and gas. Since the drug is highly effective at solidifying the stool, the dose may need adjustment if constipation becomes problematic.
Due to its binding capability, colesevelam can interfere with the absorption of other medications and fat-soluble vitamins (A, D, E, and K). To prevent this, patients should take other necessary medications or vitamin supplements at least four hours before or four hours after taking colesevelam. This separation ensures that the other substances are properly absorbed before the bile acid sequestrant can interfere.