Welchol - Drug Monograph

Introduction

Welchol (colesevelam hydrochloride) is a bile acid sequestrant medication primarily used for the management of hyperlipidemia and type 2 diabetes mellitus. As a non-systemic agent, it offers a unique mechanism of action distinct from other lipid-lowering and glucose-controlling therapies.

Mechanism of Action

Colesevelam binds bile acids in the intestinal lumen, forming an insoluble complex that is excreted in feces. This binding interrupts the enterohepatic circulation of bile acids, leading to increased hepatic conversion of cholesterol into bile acids. This process upregulates hepatic LDL receptor activity, resulting in increased clearance of LDL cholesterol from the bloodstream. For diabetes management, the mechanism is less clearly defined but may involve effects on hepatic glucose metabolism and incretin hormones.

Indications

• Primary hyperlipidemia: Adjunct to diet and exercise to reduce elevated LDL-C in adults with primary hyperlipidemia
• Type 2 diabetes mellitus: Adjunct to diet and exercise to improve glycemic control in adults
• FDA-approved pediatric use: For boys and postmenarchal girls 10-17 years old with heterozygous familial hypercholesterolemia

Dosage and Administration

• Tablets: 3 tablets twice daily or 6 tablets once daily with meals
• Oral suspension: 1 packet once daily or divided twice daily with meals

• Renal impairment: No dosage adjustment necessary
• Hepatic impairment: Use with caution; no specific dosage recommendations
• Geriatric patients: No dosage adjustment required
• Pediatric patients: 1 packet daily or divided twice daily with meals

Pharmacokinetics

Contraindications

• History of bowel obstruction
• Serum triglyceride levels >500 mg/dL
• History of hypertriglyceridemia-induced pancreatitis
• Hypersensitivity to colesevelam or any component of the formulation

Warnings and Precautions

• Hypertriglyceridemia: May increase serum triglycerides; contraindicated in patients with triglycerides >500 mg/dL
• Vitamin deficiencies: May decrease absorption of fat-soluble vitamins (A, D, E, K); consider supplementation in long-term therapy
• GI disorders: Use with caution in patients with swallowing disorders, gastrointestinal motility disorders, or major gastrointestinal surgery
• Phenylketonuria: Oral suspension contains phenylalanine (a potential concern for patients with PKU)

Drug Interactions

• Other medications: May bind and decrease absorption of numerous oral drugs including:

- Warfarin (monitor INR closely) - Cyclosporine - Thyroid hormones - Oral contraceptives - Phenytoin - Metformin - Glyburide - Levothyroxine - Verapamil

Adverse Effects

• Constipation (11%)
• Dyspepsia (8%)
• Nausea (4%)
• Hypoglycemia (in diabetic patients)
• Flatulence
• Headache

• Bowel obstruction (rare)
• Severe hypertriglyceridemia
• Pancreatitis
• Vitamin deficiencies (with long-term use)

Monitoring Parameters

• Lipid panel: LDL-C, total cholesterol, HDL-C, triglycerides at baseline and periodically
• Glycemic control: HbA1c, fasting glucose in diabetic patients
• Vitamin levels: Consider monitoring fat-soluble vitamins with long-term therapy
• GI symptoms: Monitor for constipation, abdominal discomfort
• Triglycerides: Monitor regularly, especially if baseline elevated

Patient Education

• Take with meals and plenty of fluid
• Tablets should be swallowed whole; do not cut, crush, or chew
• If taking other medications, take them at least 4 hours before Welchol
• Report severe constipation, abdominal pain, or persistent GI symptoms
• Maintain recommended diet and exercise regimen
• Diabetic patients should continue monitoring blood glucose as Welchol may cause hypoglycemia
• Notify all healthcare providers about Welchol use before starting new medications

References

1. FDA Prescribing Information: Welchol (colesevelam hydrochloride) 2. Davidson MH et al. Colesevelam hydrochloride (WelChol): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med. 1999;159(16):1893-1900. 3. Bays HE et al. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Endocr Pract. 2008;14(1):55-62. 4. Goldberg RB et al. Efficacy and safety of colesevelam in patients with type 2 diabetes mellitus and inadequate glycemic control on insulin-based therapy. Arch Intern Med. 2008;168(14):1531-1540. 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 6. Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation. 2019;139(25):e1082-e1143.