warnings and cautions
5 WARNINGS AND PRECAUTIONS The effect of WELCHOL on cardiovascular morbidity and mortality has not been determined ( 5.1 ). 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) ( 5.2 ). Bile acid sequestrants may decrease absorption of fat-soluble vitamins. Use caution in patients susceptible to fat-soluble vitamin deficiencies ( 5.3 ). 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) ( 5.4 ). WELCHOL reduces gastrointestinal absorption of some drugs. Administer drugs with a known interaction with colesevelam at least 4 hours prior to WELCHOL. Drugs that have not been tested for interaction with colesevelam, especially those with a narrow therapeutic index, should also be administered at least 4 hours prior to WELCHOL. Alternatively, monitor drug levels of the co-administered drug ( 5.5 , 7 , 12.3 ). WELCHOL for Oral Suspension contains 13.5 mg phenylalanine per 1.875 gram packet and 27 mg phenylalanine per 3.75 gram packet ( 5.6 , 11 ). 5.1 General The effect of WELCHOL on cardiovascular morbidity and mortality has not been determined. 5.2 Serum Triglycerides WELCHOL, like other bile acid sequestrants, can increase serum TG concentrations. WELCHOL had small effects on serum TG (median increase 5% compared to placebo) in trials of patients with primary hyperlipidemia [See Adverse Reactions ( 6.1 ) and Clinical Studies ( 14.1 )]. In clinical trials in patients with type 2 diabetes, greater increases in TG levels occurred when WELCHOL was used as monotherapy (median increase 9.7% compared to placebo) and when WELCHOL was used in combination with pioglitazone (median increase 11% compared to placebo in combination with pioglitazone), sulfonylureas (median increase 18% compared to placebo in combination with sulfonylureas), and insulin (median increase 22% compared to placebo in combination with insulin) [See Adverse Reactions ( 6.1 ) and Clinical Studies ( 14.2 )]. Hypertriglyceridemia of sufficient severity can cause acute pancreatitis. The long-term effect of hypertriglyceridemia on the risk of coronary artery disease is uncertain. In patients with type 2 diabetes, the effect of WELCHOL on LDL-C levels may be attenuated by WELCHOL’s effects on TG levels and a smaller reduction in non HDL-C compared to the reduction in LDL-C. Caution should be exercised when treating patients with TG levels greater than 300 mg/dL. Because most patients in the WELCHOL clinical trials had baseline TG <300 mg/dL, it is unknown whether patients with more uncontrolled baseline hypertriglyceridemia would have greater increases in serum TG levels with WELCHOL. In addition, the use of WELCHOL is contraindicated in patients with TG levels >500 mg/dL [See Contraindications ( 4 )] . Lipid parameters, including TG levels and non-HDL-C, should be obtained before starting WELCHOL and periodically thereafter. WELCHOL should be discontinued if TG levels exceed 500 mg/dL or if the patient develops hypertriglyceridemia-induced pancreatitis [See Adverse Reactions ( 6.1 )]. 5.3 Vitamin K or Fat-Soluble Vitamin Deficiencies Precautions Bile acid sequestrants may decrease the absorption of fat-soluble vitamins A, D, E, and K. No specific clinical studies have been conducted to evaluate the effects of WELCHOL on the absorption of co-administered dietary or supplemental vitamin therapy. In non-clinical safety studies, rats administered colesevelam hydrochloride at doses greater than 30-fold the projected human clinical dose experienced hemorrhage from vitamin K deficiency. Patients on oral vitamin supplementation should take their vitamins at least 4 hours prior to WELCHOL. Caution should be exercised when treating patients with a susceptibility to deficiencies of vitamin K (e.g., patients on warfarin, patients with malabsorption syndromes) or other fat-soluble vitamins. 5.4 Gastrointestinal Disorders Because of its constipating effects, WELCHOL 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. Because of the tablet size, WELCHOL Tablets can cause dysphagia or esophageal obstruction and should be used with caution in patients with dysphagia or swallowing disorders. To avoid esophageal distress, WELCHOL for Oral Suspension should not be taken in its dry form. Always mix WELCHOL for Oral Suspension with water, fruit juice, or diet soft drinks before ingesting. 5.5 Drug Interactions WELCHOL reduces gastrointestinal absorption of some drugs. Drugs with a known interaction with colesevelam should be administered at least 4 hours prior to WELCHOL. Drugs that have not been tested for interaction with colesevelam, especially those with a narrow therapeutic index, should also be administered at least 4 hours prior to WELCHOL. Alternatively, the physician should monitor drug levels of the co-administered drug [See Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )]. 5.6 Phenylketonurics WELCHOL for Oral Suspension contains 13.5 mg phenylalanine per 1.875 gram packet and 27 mg phenylalanine per 3.75 gram packet [See Description ( 11 )]. 5.7 Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular disease risk reduction with WELCHOL or any other antidiabetic drugs.