Generic Name

Welchol

Mechanism

• Bile acid sequestration: Colesevelam is a non‑absorbable polymer that binds to bile acids in the small intestine, forming insoluble complexes excreted in feces.
• Cholesterol metabolism effect: By reducing enterohepatic recirculation, hepatic bile acid synthesis increases, leading to up‑regulation of LDL‑receptor expression and enhanced LDL clearance from plasma.
• Glucose‑lowering effect: Binding bile acids activates fibroblast growth factor‑19 (FGF‑19) via the ileal FXR receptor, reducing intestinal gluconeogenesis and improving insulin sensitivity.

Pharmacokinetics

Indications

• Type 2 Diabetes Mellitus: Adjunctive therapy to improve glycemic control when diet, exercise, and other antidiabetics are insufficient.
• Hypercholesterolemia: LDL‑cholesterol reduction, especially in patients who cannot tolerate statins or require additional LDL lowering.

*Note*: Not approved for type 1 diabetes or as a primary antihyperlipidemic agent.

Contraindications

• Contraindications: Hypersensitivity to colesevelam or any component; severe, chronic diarrhea (sequestrants can worsen malabsorption of electrolytes).
• Warnings:
• Potential for decreased absorption of concomitant oral medications (e.g., levothyroxine, warfarin, oral contraceptives, statins, vitamin K‑dependent drugs).
• Hypothyroidism: monitor thyroid function tests.
• Renal impairment: no dose adjustment needed, but ensure adequate hydration.

Dosing

*Adjustment*: No dose adjustment for age, sex, liver, or renal function, but caution in patients on high‑dose lipid‑lowering regimens.

Adverse Effects

• Common (≥1 %): GI disturbances—constipation, bloating, flatulence, upper abdominal discomfort, nausea.
• Less common: Flatulence, abdominal pain, headache.
• Serious: Severe constipation or bowel obstruction (rare), hypocalcemia/hepatotoxicity (extremely rare), potential drug‑interaction‑related complications (e.g., warfarin excess, reduced levothyroxine absorption).

Monitoring

• Glycemic control: Fasting plasma glucose, HbA1c at baseline, 12 weeks, and 24 weeks.
• Lipid profile: Total cholesterol, LDL, HDL, triglyceride levels at baseline, 12 weeks, and 24 weeks.
• Thyroid function: TSH (at baseline, 3 months, 6 months if on levothyroxine).
• Co‑administered drug levels: Check warfarin INR or other drug concentrations if clinically indicated.
• Adverse effects: Monitor for GI intolerance; counsel patients on dietary fiber and adequate fluid intake.

Clinical Pearls

• Timing is key: Administer Welchol at least 1 hour before or 2 hours after other oral medications to reduce sequestration interactions.
• Synergistic lipid benefit: Adding colesevelam to a statin can lower LDL by an additional 20–25 % without increasing statin dose, ideal for statin‑intolerant patients.
• Glycemic synergy: When combined with metformin or sulfonylureas, the risk of hypoglycemia is minimal because the glucose‑lowering effect is modest and gradual.
• Patient education: Explain the possibility of bowel habit changes; recommend increasing dietary fiber and water consumption, and consider a mild laxative if constipation occurs.
• Long‑term safety: Routine monitoring of liver enzymes and creatinine is not required, but vigilance for rare hepatotoxicity is prudent in patients with pre‑existing liver disease.

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• *For further reading, consult the latest product labeling and peer‑reviewed pharmacology references. This card is for educational use only and should not replace individualized clinical advice.*