Colesevelam Hydrochloride

COLESEVELAM HYDROCHLORIDE- colesevelam hydrochloride tablet, coated
AvKARE

1 INDICATIONS AND USAGE

1.1 Primary Hyperlipidemia

Colesevelam hydrochloride is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia (Fredrickson Type IIa) as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin).

Colesevelam hydrochloride is indicated as monotherapy or in combination with a statin to reduce LDL-C levels in boys and post-menarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present:

a. LDL-C remains ≥190 mg/dL or

b. LDL-C remains ≥160 mg/dL and

• there is a positive family history of premature cardiovascular disease or
• two or more other CVD risk factors are present in the pediatric patient.

Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate [see Clinical Studies (14.1)] .

In patients with coronary heart disease (CHD) or CHD risk equivalents such as diabetes mellitus, LDL-C treatment goals are <100 mg/dL. An LDL-C goal of <70 mg/dL is a therapeutic option on the basis of recent trial evidence. If LDL-C is at goal but the serum triglyceride (TG) value is >200 mg/dL, then non-HDL cholesterol (non-HDL-C) (total cholesterol [TC] minus high density lipoprotein cholesterol [HDL-C]) becomes a secondary target of therapy. The goal for non-HDL-C in persons with high serum TG is set at 30 mg/dL higher than that for LDL-C.

1.3 Important Limitations of Use

• Colesevelam hydrochloride should not be used for the treatment of type 1 diabetes or for the treatment of diabetic ketoacidosis.
• Colesevelam hydrochloride has not been studied in type 2 diabetes in combination with a dipeptidyl peptidase 4 inhibitor.
• Colesevelam hydrochloride has not been studied in pediatric patients with type 2 diabetes.
• Colesevelam hydrochloride has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias.
• Colesevelam hydrochloride has not been studied in children younger than 10 years of age or in pre-menarchal girls.

2 DOSAGE AND ADMINISTRATION

2.1 Primary Hyperlipidemia

The recommended dose of colesevelam hydrochloride tablets in adults, whether used as monotherapy or in combination with a statin, is 6 tablets once daily or 3 tablets twice daily. Colesevelam hydrochloride tablets should be taken with a meal and liquid.

Colesevelam hydrochloride can be dosed at the same time as a statin or the two drugs can be dosed apart [see Clinical Studies (14.1)] .

After initiation of colesevelam hydrochloride, lipid levels should be analyzed within 4 to 6 weeks.

3 DOSAGE FORMS AND STRENGTHS

• 625 mg tablets are off-white to pale yellow film-coated oval tablets, debossed with “L61” on one side and plain on the other side.

4 CONTRAINDICATIONS

Colesevelam hydrochloride is contraindicated in patients with

• A history of bowel obstruction [see Warnings and Precautions (5.4)]
• Serum TG concentrations >500 mg/dL [see Warnings and Precautions (5.2)]
• A history of hypertriglyceridemia-induced pancreatitis [see Warnings and Precautions (5.2)]

5 WARNINGS AND PRECAUTIONS

5.1 General

The effect of colesevelam hydrochloride on cardiovascular morbidity and mortality has not been determined.

5.2 Serum Triglycerides

Colesevelam hydrochloride, like other bile acid sequestrants, can increase serum TG concentrations.

Colesevelam hydrochloride 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)] .

Hypertriglyceridemia of sufficient severity can cause acute pancreatitis. The long-term effect of hypertriglyceridemia on the risk of coronary artery disease is uncertain. Caution should be exercised when treating patients with TG levels greater than 300 mg/dL. Because most patients in the colesevelam hydrochloride 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 colesevelam hydrochloride. In addition, the use of colesevelam hydrochloride 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 colesevelam hydrochloride and periodically thereafter. Colesevelam hydrochloride 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 colesevelam hydrochloride on the absorption of co-administered dietary or supplemental vitamin therapy. In nonclinical 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 colesevelam hydrochloride. 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, 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. Because of the tablet size, colesevelam hydrochloride tablets can cause dysphagia or esophageal obstruction and should be used with caution in patients with dysphagia or swallowing disorders.

5.5 Drug Interactions

Colesevelam hydrochloride reduces gastrointestinal absorption of some drugs. Drugs with a known interaction with colesevelam should be administered at least 4 hours prior to colesevelam hydrochloride. 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 colesevelam hydrochloride. Alternatively, the physician should monitor drug levels of the co-administered drug [see Drug Interactions (7) and Clinical Pharmacology (12.3)] .

5.7 Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular disease risk reduction with colesevelam hydrochloride or any other antidiabetic drugs.

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in clinical studies of another drug and may not reflect the rates observed in practice.