COLESEVELAM HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Colesevelam hydrochloride is a bile acid sequestrant that binds bile acids in the intestine, forming an insoluble complex excreted in feces. This reduces enterohepatic circulation of bile acids, leading to increased conversion of cholesterol to bile acids in the liver and upregulation of LDL receptors, resulting in decreased serum LDL cholesterol. In diabetes, it improves glycemic control possibly by altering bile acid signaling via FXR and TGR5 receptors, affecting hepatic glucose production and incretin release.
| Metabolism | Colesevelam is not systemically absorbed (<0.05%) and undergoes negligible metabolism. |
| Excretion | Colesevelam is not absorbed systemically; it is excreted unchanged in the feces via biliary elimination. No renal excretion occurs. |
| Half-life | Not applicable as colesevelam is not absorbed; it acts locally in the gastrointestinal tract. |
| Protein binding | 0% (not absorbed; no systemic protein binding). |
| Volume of Distribution | Not applicable; drug is not systemically absorbed and remains confined to the gastrointestinal lumen. |
| Bioavailability | <0.1% after oral administration; essentially not absorbed. |
| Onset of Action | Reduction in LDL-C is observed within 2 weeks of oral administration, with maximal effect typically seen after 4-6 weeks. |
| Duration of Action | Duration of lipid-lowering effect persists as long as therapy is continued; effect reverses upon discontinuation due to local action in the gut. |
3.75 g orally once daily or divided as 1.875 g twice daily with meals and liquid; maximum 4.375 g/day.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No dose adjustment required for renal impairment; not systemically absorbed. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; use with caution due to potential for constipation and gastrointestinal obstruction. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Can decrease the absorption of many other drugs (eg warfarin phenytoin) administer other drugs 4 hours before colesevelam Can cause constipation and may increase triglycerides.
| Breastfeeding | Colesevelam is not absorbed systemically; therefore, excretion into breast milk is negligible. M/P ratio: not applicable. Considered compatible with breastfeeding by most sources. |
| Teratogenic Risk | Colesevelam hydrochloride is not systemically absorbed (<0.05% oral bioavailability). No fetal risk is expected. No adequate and well-controlled studies in pregnant women. Based on animal studies, no evidence of harm at doses up to 1.5 times human dose. Insufficient data for first trimester; however, given negligible absorption, teratogenic risk is considered negligible across all trimesters. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | type 2 diabetes |
| Serious Effects |
["Bowel obstruction or history of bowel obstruction","Hypertriglyceridemia-induced pancreatitis","Elevated serum triglycerides >500 mg/dL","Hypersensitivity to colesevelam or any component"]
| Precautions | ["May cause hypertriglyceridemia (monitor triglycerides)","Risk of fat-soluble vitamin deficiency (Vitamins A, D, E, K) with prolonged use","May reduce absorption of: oral contraceptives, cyclosporine, warfarin, thyroid hormone, and other drugs (administer 4 hours before or after Colesevelam)","Patients with hemorrhoids or history of severe GI obstruction risk","May cause constipation, dyspepsia, and abdominal pain"] |
| Food/Dietary | Take with meals to enhance bile acid binding. Avoid high-fat meals that may reduce efficacy. Colesevelam may interfere with absorption of fat-soluble vitamins (A, D, E, K); consider supplementation if long-term use. Grapefruit juice has no documented interaction. |
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| Fetal Monitoring | No specific monitoring required beyond routine obstetric care. Monitor maternal lipid profiles as clinically indicated. Monitor for potential interactions with fat-soluble vitamins (A, D, E, K) and folic acid; consider monitoring levels if long-term therapy. |
| Fertility Effects | No known effects on fertility in humans. Animal studies at doses up to 1.5 times human dose showed no impairment of fertility. |
| Clinical Pearls | Colesevelam is a bile acid sequestrant that reduces LDL-C and improves glycemic control in type 2 diabetes. Administer with meals to maximize bile acid binding. Monitor triglycerides as levels may increase. Separate dosing from other medications (e.g., levothyroxine, warfarin) by at least 4 hours to avoid reduced absorption. Can be mixed with water, fruit juice, or soft foods. |
| Patient Advice | Take this medication with a meal and at least 4 hours after any other medications. · Mix powder with 4-8 ounces of water, fruit juice, or soft food (e.g., applesauce) and consume within 24 hours. · Do not take without food; it may cause stomach upset. · Common side effects include constipation, gas, and indigestion; drink plenty of fluids and increase fiber intake. · This medication can increase triglyceride levels; your doctor will monitor your blood. · Inform your doctor if you have a history of pancreatitis or gallbladder disease. · Keep out of reach of children and store at room temperature. |