Colesevelam
Regulatory sources consulted
Approved indications
- Adjunct to diet in adults with primary hypercholesterolemia: with a statin for additional LDL-C reduction, as monotherapy when a statin is inappropriate or not tolerated, or with ezetimibe with or without a statin.
Contraindications
Absolute
- Hypersensitivity to colesevelam or excipients.
- History of bowel obstruction (FDA); bowel or biliary obstruction (CIMA).
- Serum triglycerides above 500 mg/dL (FDA contraindication).
- History of hypertriglyceridemia-induced pancreatitis (FDA contraindication).
Clinical warnings
- Major warning · Triglycerides may increase; use caution when they exceed 3.4 mmol/L and monitor them regularly. — https://cima.aemps.es/cima/dochtml/ft/03268004/FT_03268004.html
- Major warning · It may cause or worsen constipation; assess risk particularly in coronary heart disease or angina. Use caution with dysphagia, gastrointestinal motility disorders, inflammatory bowel disease, hepatic impairment or major gastrointestinal surgery. — https://cima.aemps.es/cima/dochtml/ft/03268004/FT_03268004.html
- Major warning · Closely monitor cyclosporine and warfarin anticoagulation; changes when starting or stopping colesevelam may alter their effects. — https://cima.aemps.es/cima/dochtml/ft/03268004/FT_03268004.html
- Major warning · It may reduce absorption of the fat-soluble vitamins A, D, E, and K; oral supplements of these vitamins should be administered at least 4 hours before colesevelam. Use particular caution in patients with malabsorption and monitor INR with warfarin, especially when starting or stopping colesevelam. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d1b8dfd-cfe7-4c86-9d7b-a709b593acf7
Drug interactions
- ModerateCyclosporine, phenytoin, thyroid hormones, contraceptives containing ethinyl estradiol and norethindrone, olmesartan, and sulfonylureas
Mechanism: Colesevelam may reduce exposure to cyclosporine, phenytoin, levothyroxine or other thyroid hormones, ethinyl estradiol and norethindrone, olmesartan, and the sulfonylureas glimepiride, glipizide, and glyburide.
Recommendation: Administer these medicines at least 4 hours before colesevelam; monitor levels or clinical response when appropriate.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d1b8dfd-cfe7-4c86-9d7b-a709b593acf7
- ModerateWarfarinB01AA03
Mechanism: Colesevelam may decrease warfarin exposure; reduced INR has been reported during concomitant treatment.
Recommendation: Administer warfarin at least 4 hours before colesevelam and monitor INR frequently when starting colesevelam and periodically thereafter.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d1b8dfd-cfe7-4c86-9d7b-a709b593acf7
- ModerateUnstudied oral medicines or medicines with a narrow therapeutic index
Mechanism: Gastrointestinal binding by colesevelam may reduce the bioavailability of an oral medicine when the interaction has not been studied or cannot be excluded.
Recommendation: FDA: consider administering it at least 4 hours before colesevelam. CIMA: if an interaction cannot be excluded, administer it at least 4 hours before or 4 hours after. This separation does not apply to extended-release metformin, which requires glycemic monitoring as described in its specific entry.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d1b8dfd-cfe7-4c86-9d7b-a709b593acf7https://cima.aemps.es/cima/dochtml/ft/03268004/FT_03268004.html
- ModerateExtended-release metformin
Mechanism: Co-administration increases metformin exposure.
Recommendation: Monitor the usual glycemic response to antidiabetic treatment and adjust according to clinical assessment.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d1b8dfd-cfe7-4c86-9d7b-a709b593acf7
Adverse events
Common (≥1%)
Flatulence · Constipation · Headache · Vomiting · Diarrhea · Dyspepsia · Abdominal pain or distension · Nausea · Increased triglycerides
Rare but serious
Pancreatitis · Intestinal obstruction
Pregnancy and lactation
Use caution during pregnancy and breastfeeding; safety has not been established in these populations.
Recent literature (PubMed)
Bile acid diarrhea is a common cause of bowel symptoms and often goes unrecognized or misdiagnosed. Many aspects of management remain contentious. The primary, idiopathic condition should be suspected in people with functional diarrhea or diarrhea-predominant irritable bowel syndrome. Secondary causes include ileal resection, inflammation, and post-cholecystectomy. Diagnostic tests vary globally, being unavailable in many countries, and further refinement of testing strategy is needed. Management is usually long-term symptom control, rather than reversal of the causative factors, which are still being defined. Bile acid sequestrants remain the main drugs used. They are relatively inexpensive, and better-quality data is now available for colesevelam. However, optimal use, including timing and formulation, needs clarification. The GLP-1 receptor agonist, liraglutide, is also effective, although mechanisms of action and whether this effect is common to other class members is unclear. They are more expensive, and availability varies. FXR agonists can also be effective but require further validation. The role of dietary factors in symptom development is a major patient concern, needing more formal studies. To build on recent findings, bile acid diarrhea needs further investment into causes, diagnosis and therapy to guide present and future patient care. The condition known as bile acid diarrhea (BAD) causes frequent loose stools, which need to be passed urgently, sometimes causing incontinence. It can be a complication of surgery or other intestinal disorders, and gives similar symptoms to IBS. It is not widely known and clinicians often fail to diagnose it. In this article, we review recent publications about how to make the diagnosis of BAD. Some of these are contentious and there may be limited availability of the tests or poor accuracy. We then review current treatments and how to best manage BAD. There are some new treatments, which are not yet fully proven or accep
Low anterior resection syndrome (LARS) is a series of bowel dysfunction symptoms, including altered bowel frequency, irregular bowel rhythms, fecal incontinence, and constipation. LARS occurs in 80% of patients undergoing sphincter-preserving surgery, affecting patients' quality of life along with social avoidance. Different measurements and treatments have been raised to deal with LARS, but no systematic standard has been developed. To promote the standardization of clinical trials and clinical management of LARS, this review summarizes the latest findings up until 2023 regarding the diagnostic criteria, assessment protocols, and treatment modalities for postoperative LARS in rectal cancer. The diagnostic criteria for LARS need to be updated to the definition proposed by the LARS International Collaborative Group, replacing the current application of the LARS score. In both clinical trials and clinical treatment, the severity of LARS should be assessed using at least one symptom assessment questionnaire, the LARS score or MSKCC BFI, and at least one scale related to quality of life. Anorectal manometry, fecoflowmetry, endoscopic ultrasonography, and pelvic floor muscle strength testing are recommended to be adopted only in clinical trials. After analysis of the latest literature on LARS treatment, a stepwise classification model is established for the standardized clinical management of LARS. Patients with minor LARS can start with first-line treatment, including management of self-behavior with an emphasis on diet modification and medication. Lamosetron, colesevelam hydrochloride, and loperamide are common antidiarrheal agents. Second-line management indicates multi-mode pelvic floor rehabilitation and transanal irrigation. Patients with major LARS should select single or several treatments in second-line management. Refractory LARS can choose antegrade enema, neuromodulation, or colostomy. In clinical trials of LARS treatment between 2020 and 2022, the eligibilit
The aim of this paper is to raise awareness of MC as a clinically significant condition and to highlight its under-recognition, risk factors, diagnosis, management, and complications. This paper underlines the diagnostic and therapeutic challenges associated with the often nonspecific symptoms of MC. In order to create this article, we reviewed available articles found in the PubMed database and searched for articles using the Google Scholar platform. Microscopic colitis (MC) is a chronic inflammatory bowel disease, classified into three types: lymphocytic, collagenous, and unspecified. The average age of onset of MC is around 62-65 years and the disease is more common in women than men (nine times more common). The main symptom of MC is watery diarrhoea without blood, other symptoms include defecatory urgency, faecal incontinence, abdominal pain, nocturnal bowel movements, and weight loss. Once considered a rare disease, MC is now being diagnosed with increasing frequency, but diagnosis remains difficult. To date, a number of causative factors for MC have been identified, including smoking, alcohol consumption, medications (including NSAIDs, PPIs, SSRIs, and ICPIs), genetic factors, autoimmune diseases, bile acid malabsorption, obesity, appendicitis, and intestinal dysbiosis. It may be difficult to recognize and should be differentiated from inflammatory bowel diseases (Crohn's disease and ulcerative colitis), irritable bowel syndrome (IBS), coeliac disease, infectious bowel disease, and others. Diagnosis involves biopsy at colonoscopy and histopathological evaluation of the samples. Treatment consists of budesonide oral (the gold standard) or enema. Alternatives include bile acid sequestrants (cholestyramine, colesevelam, and colestipol), biologics (infliximab, adalimumab, and vedolizumab), thiopurines, methotrexate, and rarely, surgery.