WELCHOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WELCHOL (WELCHOL).
Welchol (colesevelam) is a bile acid sequestrant. It binds to bile acids in the intestine, forming an insoluble complex that is excreted in the feces. This disrupts the enterohepatic circulation of bile acids, leading to increased hepatic conversion of cholesterol to bile acids, resulting in decreased serum low-density lipoprotein cholesterol (LDL-C). Additionally, colesevelam may improve glycemic control in type 2 diabetes by binding to bile acids, which alters farnesoid X receptor (FXR) and TGR5 signaling, leading to increased glucagon-like peptide-1 (GLP-1) secretion and improved insulin sensitivity.
| Metabolism | Colesevelam is not absorbed systemically and therefore not metabolized by hepatic cytochrome P450 enzymes. It acts locally in the gastrointestinal tract and is excreted unchanged in the feces. |
| Excretion | Primarily fecal as unchanged drug (approximately 85%), with less than 0.5% renal excretion of absorbed drug; no biliary excretion due to non-absorbed nature. |
| Half-life | Not applicable; colesevelam acts locally in the gastrointestinal tract and is not absorbed systemically. Terminal half-life is not measurable in conventional pharmacokinetic sense due to negligible systemic absorption. |
| Protein binding | <0.1% (negligible systemic absorption results in minimal protein binding; colesevelam is a non-absorbed polymer). |
| Volume of Distribution | Not applicable (colesevelam is not systemically absorbed; Vd cannot be determined and is clinically irrelevant). |
| Bioavailability | Oral bioavailability <0.5% (negligible systemic absorption); drug acts locally in gastrointestinal tract. |
| Onset of Action | Pharmacodynamic effect on LDL-C reduction observed within 2 weeks with maximal effect by 4-6 weeks after oral administration. |
| Duration of Action | Duration of LDL-C lowering effect persists as long as therapy continues; after discontinuation, LDL-C levels return to baseline within several weeks. |
Adults: 625 mg to 1.875 g orally twice daily, with meals. Maximum 4.375 g/day.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment needed for renal impairment. |
| Liver impairment | Not recommended in patients with bowel obstruction or severe hepatic impairment; no specific Child-Pugh guidelines. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment; use with caution due to potential constipation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WELCHOL (WELCHOL).
| Breastfeeding | Colesevelam is not absorbed systemically and is not expected to be excreted into breast milk. No human studies are available. The M/P ratio is unknown but likely extremely low due to lack of absorption. Caution is advised, but risk to nursing infant is minimal. Monitor infant for signs of vitamin deficiency if mother is on long-term therapy. |
| Teratogenic Risk | Welchol (colesevelam) is a bile acid sequestrant. In animal studies, no evidence of teratogenicity was observed at doses up to 3 times the human dose. Human data are limited. The drug is not absorbed systemically, so fetal exposure is negligible. However, it may reduce absorption of fat-soluble vitamins (A, D, E, K), which are essential for fetal development. Insufficient vitamin K can cause neonatal coagulopathy. Therefore, potential risk of fetal harm is low but theoretical if maternal vitamin deficiency occurs. FDA Pregnancy Category B. |
■ FDA Black Box Warning
None
| Serious Effects |
["History of hypersensitivity to colesevelam or any component of the formulation","Bowel obstruction","Serum triglyceride level >500 mg/dL"]
| Precautions | ["May increase serum triglycerides; use with caution in patients with hypertriglyceridemia, particularly when triglyceride levels exceed 300 mg/dL, as it may cause severe hypertriglyceridemia and pancreatitis.","May decrease absorption of fat-soluble vitamins (A, D, E, K) and folic acid; monitor and consider supplementation if necessary.","May cause gastrointestinal adverse effects such as constipation, dyspepsia, and abdominal pain; patients should be advised to increase fluid and fiber intake.","May reduce absorption of orally administered drugs; administer other medications at least 4 hours before Welchol or consider separating by longer intervals.","Use with caution in patients with swallowing disorders or gastrointestinal motility disorders.","Not recommended for patients with pre-existing hypertriglyceridemia (triglycerides >500 mg/dL) due to risk of severe elevation."] |
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| Fetal Monitoring | Maternal monitoring: Assess serum total cholesterol, LDL-C, and triglycerides at baseline and periodically. Monitor for gastrointestinal side effects (constipation, dyspepsia). Check for drug interactions, particularly with thyroid hormone and oral contraceptives. Fetal/neonatal monitoring: No specific monitoring required, but ensure maternal intake of fat-soluble vitamins (A, D, E, K) is adequate. Consider coagulation studies in neonate if prolonged maternal use. |
| Fertility Effects | No known effects on fertility in animal studies. In humans, no fertility studies are reported. The drug is not systemically absorbed, so direct reproductive toxicity is unlikely. However, potential for vitamin malabsorption could theoretically affect reproductive function, but no evidence of such. |