Colesevelam

Colesevelam hydrochloride 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. reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia (HeFH), unable to reach LDL-C target levels despite an adequate trial of diet and lifestyle modification. improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Do not use for treatment of type 1 diabetes or for diabetic ketoacidosis. Not studied in Fredrickson Type I, III, IV, and V dyslipidemias

Primary Hyperlipidemia: Colesevelam hydrochloride, the active pharmaceutical ingredient, 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.

Obtain lipid parameters, including serum triglyceride (TG) levels, before starting colesevelam hydrochloride. The recommended dosage for adults and for boys and postmenarchal girls aged 10 to 17 years with primary hyperlipidemia is 3.75 grams daily. The recommended dosage for adults with type 2 diabetes mellitus is 3.75 grams daily. Colesevelam hydrochloride should be taken as follows: Tablets Take 6 tablets once daily or 3 tablets twice daily with a meal and liquid. For Oral Suspension Take one packet once daily with a meal. To prepare, empty the entire contents of one packet into a glass or cup. Add 1 cup of water, fruit juice, or diet soft drinks. Stir well and drink.

Colesevelam hydrochloride is contraindicated in patients with: Serum TG concentrations >500 mg/dL History of hypertriglyceridemia-induced pancreatitis A history of bowel obstruction Patients with serum triglyceride levels >500 mg/dL. Patients with a history of hypertriglyceridemia-induced pancreatitis. Patients with a history of bowel obstruction

Hypertriglyceridemia and Pancreatitis: Colesevelam hydrochloride can increase TG. Hypertriglyceridemia can cause acute pancreatitis. Monitor lipids, including TG. Instruct patients to discontinue colesevelam hydrochloride and seek prompt medical attention if the symptoms of acute pancreatitis occur. Gastrointestinal Obstruction: Cases of bowel obstruction have occurred. Colesevelam hydrochloride is not recommended in patients with gastroparesis, other gastrointestinal motility disorders, and in those who have had major gastrointestinal tract surgery and who may be at risk for bowel obstruction. Vitamin K or Fat-Soluble Vitamin Deficiencies: Colesevelam hydrochloride may decrease absorption of fat-soluble vitamins.

The following important adverse reactions are described below and elsewhere in the labeling: Hypertriglyceridemia and Pancreatitis Gastrointestinal Obstruction Vitamin K or Fat-Soluble Vitamin Deficiencies In clinical trials, the most common (incidence ≥2% and greater than placebo) adverse reactions with colesevelam hydrochloride included constipation, dyspepsia, and nausea.

Concomitant use with colesevelam hydrochloride may decrease the exposure of the following drugs: Drugs with a narrow therapeutic index (e.g., cyclosporine), phenytoin, thyroid hormone replacement therapy, warfarin, oral contraceptives containing ethinyl estradiol and norethindrone, olmesartan medoxomil, and sulfonylureas (glimepiride, glipizide, glyburide). Administer these drugs 4 hours prior to colesevelam hydrochloride. For patients on warfarin, monitor International Normalized Ratio (INR) frequently during initiation then periodically. Concomitant use with colesevelam hydrochloride may increase the exposure of the following drugs: Metformin extended release. Monitor patients' glycemic control.