Primary Hyperlipidemia: Colesevelam hydrochloride, the active pharmaceutical ingredient in WELCHOL, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 7-α-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids. This causes an increased demand for cholesterol in the liver cells, resulting in the dual effect of increasing transcription and activity of the cholesterol biosynthetic enzyme, HMG-CoA reductase, and increasing the number of hepatic LDL receptors. These compensatory effects result in increased clearance of LDL-C from the blood, resulting in decreased serum LDL-C levels. Serum TG levels may increase or remain unchanged. Type 2 Diabetes Mellitus: The mechanism by which WELCHOL improves glycemic control is unknown.

WELCHOL is a bile acid sequestrant indicated as an adjunct to diet and exercise to
• reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin)
• reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia as monotherapy or in combination with a statin after failing an adequate trial of diet therapy
• improve glycemic control in adults with type 2 diabetes mellitus See package insert for complete information.

• WELCHOL Tablets: The recommended dose is 6 tablets once daily or 3 tablets twice daily. WELCHOL Tablets should be taken with a meal and liquid.
• WELCHOL for Oral Suspension: The recommended dose is one 3.75 gram packet once daily or one 1.875-gram packet twice daily. To prepare, empty the entire contents of one packet into a glass or cup. Add ½ to 1 cup (4 to 8 ounces) of water, fruit juice, or diet soft drinks. Stir well and drink. WELCHOL for Oral Suspension should be taken with meals. To avoid esophageal distress, WELCHOL for Oral Suspension should not be taken in its dry form.

In clinical trials, the most common (incidence ≥2% and greater than placebo) adverse reactions with WELCHOL included constipation, dyspepsia, and nausea. In the diabetes trials, the overall incidence of hypoglycemia was 3.0% in WELCHOL-treated patients and 2.3% in placebo-treated patients. See package insert for complete information.

Do not use in patients with a history of bowel obstruction • Do not use in patients with serum triglyceride (TG) concentrations >500 mg/dL.
• Do not use in patients with a history of hypertriglyceridemia-induced pancreatitis.

• The effect of WELCHOL on cardiovascular morbidity and mortality has not been determined.
• WELCHOL can increase TG, particularly when used with insulin or sulfonylureas. Marked hypertriglyceridemia can cause acute pancreatitis. The effect of hypertriglyceridemia on the risk of coronary artery disease is uncertain. Monitor lipids, including TG and non-high-density lipoprotein cholesterol (non-HDL-C)
• Bile acid sequestrants may decrease the absorption of fat-soluble vitamins. Use caution in patients susceptible to fat-soluble vitamin deficiencies.
• Because of its constipating effects, WELCHOL is not recommended in patients at risk of bowel obstruction (e.g., patients with gastroparesis, other gastrointestinal motility disorders, or a history of major gastrointestinal surgery). See package insert for complete information.