These Highlights Do Not Include All The Information Needed To Use Colesevelam Hydrochloride Safely And Effectively. See Full Prescribing Information For Colesevelam Hydrochloride.

Tablets

Take 6 tablets once daily or 3 tablets twice daily. Due to tablet size, colesevelam hydrochloride for oral suspension is recommended for use in the pediatric population.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture. Brief exposure to 40°C (104°F) does not adversely affect colesevelam hydrochloride tablets.

Colesevelam hydrochloride is not absorbed and the risk of systemic toxicity is low. Excessive doses of colesevelam hydrochloride may cause more severe local gastrointestinal effects (e.g., constipation).

Colesevelam hydrochloride is a non-absorbed, polymeric, lipid-lowering and glucose-lowering agent for oral administration. Colesevelam hydrochloride is a high-capacity bile acid-binding molecule.

Colesevelam hydrochloride is poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and (6-bromohexyl)-trimethylammonium bromide. The chemical name (IUPAC) of colesevelam hydrochloride is allylamine polymer with 1-chloro-2,3-epoxypropane,[6-(allylamino)-hexyl] trimethylammonium chloride and N-allyldecylamine, hydrochloride. The chemical structure of colesevelam hydrochloride is represented by the following formula:

wherein (a) represents allyl amine monomer units that have not been alkylated by either of the 1-bromodecane or (6-bromohexyl)-trimethylammonium bromide alkylating agents or cross-linked by epichlorohydrin; (b) represents allyl amine units that have undergone cross-linking with epichlorohydrin; (c) represents allyl amine units that have been alkylated with a decyl group; (d) represents allyl amine units that have been alkylated with a (6-trimethylammonium) hexyl group, and m represents a number ≥100 to indicate an extended polymer network. A small amount of the amines are dialkylated and are not depicted in the formula above. No regular order of the groups is implied by the structure; cross-linking and alkylation are expected to occur randomly along the polymer chains. A large amount of the amines are protonated. The polymer is depicted in the hydrochloride form; a small amount of the halides are bromide. Colesevelam hydrochloride is hydrophilic and insoluble in water.

Colesevelam hydrochloride tablets are off-white, oval, film-coated, solid tablets each containing 625 mg colesevelam hydrochloride. In addition, each tablet contains the following inactive ingredients: magnesium stearate, microcrystalline cellulose, silicon dioxide, HPMC (hydroxypropyl methylcellulose), and acetylated monoglyceride. The tablets are imprinted using a water-soluble black ink (<5 calories per 6 tablets).

Colesevelam hydrochloride for oral suspension is a citrus-flavored, white to pale yellow powder containing yellow granules packaged in a packet containing 3.75 gram colesevelam hydrochloride. In addition, each packet contains the following inactive ingredients: lemon flavor, orange flavor, propylene glycol alginate, simethicone, aspartame, citric acid, medium chain triglycerides, and magnesium trisilicate (<5 calories per 3.75 gram single-dose packet). PHENYLKETONURICS: Colesevelam hydrochloride for oral suspension contains 27 mg phenylalanine per 3.75 gram dose.

Colesevelam hydrochloride is contraindicated in patients with:

• Serum TG concentrations >500 mg/dL [see Warnings and Precautions (5.1)]
• History of hypertriglyceridemia-induced pancreatitis [see Warnings and Precautions (5.1)]
• A history of bowel obstruction [see Warnings and Precautions (5.2)]

The following important adverse reactions are described below and elsewhere in the labeling:

• Hypertriglyceridemia and Pancreatitis [see Warnings and Precautions (5.1)]
• Gastrointestinal Obstruction [see Warnings and Precautions (5.2)]
• Vitamin K or Fat-Soluble Vitamin Deficiencies [see Warnings and Precautions (5.3)]

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 ( 7.1).

Concomitant use with colesevelam hydrochloride may increase the exposure of the following drugs:Metformin extended release. Monitor patients' glycemic control ( 7.2).

A maximum therapeutic response to the lipid-lowering effects of colesevelam hydrochloride was achieved within 2 weeks and was maintained during long-term therapy. In the diabetes clinical studies, a therapeutic response to colesevelam hydrochloride, as reflected by a reduction in HbA1c, was initially noted following 4-6 weeks of treatment and reached maximal or near-maximal effect after 12-18 weeks of treatment.

Colesevelam hydrochloride reduces gastrointestinal absorption of some drugs. Administer drugs with a known interaction at least 4 hours prior to colesevelam hydrochloride [see Drug Interactions (7)] .

Due to the potential for decreased absorption of other drugs that have not been tested for interaction, especially those with a narrow therapeutic index, consider administering at least 4 hours prior to colesevelam hydrochloride [see Clinical Pharmacology (12.3)].

• 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 Fredrickson Type I, III, IV, and V dyslipidemias.

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 ( 1.1).
• 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 ( 1.1).
• improve glycemic control in adults with type 2 diabetes mellitus ( 1.2).

Limitations of Use ( 1.3):

• Do not use for treatment of type 1 diabetes or for diabetic ketoacidosis.
• Not studied in Fredrickson Type I, III, IV, and V dyslipidemias

NDC 0713-0936-81

Colesevelam Hydrochloride

Tablets

625 mg

180 Tablets

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.

Colesevelam hydrochloride is indicated to reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia (HeFH) who are unable to reach LDL-C target levels despite an adequate trial of dietary therapy and lifestyle modification.

• 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 ( 5.1).
• 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 ( 5.2).
• Vitamin K or Fat-Soluble Vitamin Deficiencies: Colesevelam hydrochloride may decrease absorption of fat-soluble vitamins. Patients with a susceptibility to deficiencies of vitamin K (e.g., patients on warfarin, patients with malabsorption syndromes) or other fat-soluble vitamins may be at increased risk. Patients on oral vitamin supplementation should take their vitamins at least 4 hours prior to colesevelam hydrochloride ( 5.3).
• Drug Interactions:Due to the potential for decreased absorption of other drugs that have not been tested for interaction, consider administering at least 4 hours prior to colesevelam hydrochloride ( 5.4, 7, 12.3).
• Risks in Patients with Phenylketonuria (PKU):Phenylalanine can be harmful to patients with phenylketonuria. Colesevelam hydrochloride for oral suspension contains 27 mg phenylalanine per 3.75 gram packet ( 5.5, 11).

Colesevelam hydrochloride reduces total cholesterol (TC), LDL-C, apolipoprotein B (Apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) when administered alone or in combination with a statin in patients with primary hyperlipidemia.

Approximately 1600 patients were studied in 9 clinical trials with treatment durations ranging from 4 to 50 weeks. With the exception of one open-label, uncontrolled, long-term extension study, all studies were multicenter, randomized, double-blind, and placebo-controlled. A maximum therapeutic response to colesevelam hydrochloride was achieved within 2 weeks and was maintained during long-term therapy.

• Obtain lipid parameters, including serum triglyceride (TG) levels, before starting colesevelam hydrochloride ( 2.1).
• 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 ( 2.2, 2.4):

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 indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus .

• Tablets: 625 mg tablets are off-white, oval, film-coated and imprinted with "Sankyo" and "C01" on one side.
• For Oral Suspension: 3.75 gram packet containing a white to pale yellow powder with yellow granules.

Colesevelam hydrochloride has been studied as monotherapy and in combination with metformin, pioglitazone, sulfonylureas, and insulin. In these studies, colesevelam hydrochloride and placebo were administered either as 3 tablets twice daily with lunch and dinner or as 6 tablets with dinner alone.

The following additional adverse reactions have been identified during post-approval use of colesevelam hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse Reactions Resulting from Drug Interactions [see Drug Interactions (7)]: Increased seizure activity or decreased phenytoin levels in patients receiving phenytoin, reduced International Normalized Ratio (INR) in patients receiving warfarin therapy, and elevated thyroid-stimulating hormone (TSH) in patients receiving thyroid hormone replacement therapy

Gastrointestinal: Bowel obstruction (in patients with a history of bowel obstruction or resection), dysphagia or esophageal obstruction (occasionally requiring medical intervention), fecal impaction, pancreatitis, abdominal distension, exacerbation of hemorrhoids, and increased transaminases

Laboratory Abnormalities:Hypertriglyceridemia

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.

Postmarketing cases of bowel obstruction have occurred with colesevelam hydrochloride [see Adverse Reactions (6.2)] . 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. Colesevelam hydrochloride is contraindicated in patients with a history of bowel obstruction [see Contraindications (4)] . Instruct patients to promptly discontinue colesevelam hydrochloride and seek medical attention if severe abdominal pain or severe constipation occurs.

Because of the tablet size, colesevelam hydrochloride tablets can cause dysphagia or esophageal obstruction. For patients with difficulty swallowing tablets, use colesevelam hydrochloride for oral suspension.

Colesevelam hydrochloride 625 mg tablets are supplied as off-white, solid tablets imprinted with the word "Sankyo" and "C01" on one side and are available as follows:

• Bottles of 180 – NDC 0713-0936-81

Colesevelam hydrochloride 3.75 gram packets for oral suspension contain a white to pale yellow powder containing yellow granules and are available as follows:

• Cartons of 30 packets – NDC 0713-0935-30

Colesevelam hydrochloride, like other bile acid sequestrants, can increase serum TG concentrations. Hypertriglyceridemia can cause acute pancreatitis.

Colesevelam hydrochloride had effects on serum TG (median increase 5% compared to placebo) in trials of patients with primary hyperlipidemia.

In trials in patients with type 2 diabetes, greater increases in TG levels occurred when colesevelam hydrochloride was used as monotherapy (median increase 9.7% compared to placebo) and when colesevelam hydrochloride 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)].

Obtain lipid parameters, including TG levels, before starting colesevelam hydrochloride and periodically thereafter. Colesevelam hydrochloride is contraindicated in patients with TG levels >500 mg/dL or patients with a history of hypertriglyceridemia-induced pancreatitis [see Contraindications (4)] . Patients with TG levels greater than 300 mg/dL could have greater increases in serum TG levels with colesevelam hydrochloride and may require additional TG monitoring. Instruct patients to discontinue colesevelam hydrochloride and seek prompt medical attention if the symptoms of acute pancreatitis occur (e.g., severe abdominal pain with or without nausea and vomiting). Discontinue colesevelam hydrochloride if TG levels exceed 500 mg/dL [see Adverse Reactions (6.1)] .

TEAR HERE

No cutting required

Sugar-Free

This packet is contained within the

CARTON NDC 0713-0935-30

Rx only

Colesevelam

Hydrochloride

for Oral Suspension

3.75 g

Citrus Flavor

Single-Dose Packet

Each packet contains 3.75 grams of

colesevelam hydrochloride.

Keep Out of Reach of Children.

Package Not Child Resistant.

NDC 0713-0935-30

Rx only

30 packets

Colesevelam

Hydrochloride

for Oral Suspension

3.75 g

Each packet contains 3.75 grams of

colesevelam hydrochloride.

Dosing and use: see package insert.

Keep Out of Reach of Children.

Package Not Child Resistant.

Phenylalanine can be harmful to patients with PKU. Colesevelam hydrochloride for oral suspension contains phenylalanine, a component of aspartame. Each 3.75 gram packet contains 27 mg of phenylalanine. Before prescribing colesevelam hydrochloride for oral suspension to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including colesevelam hydrochloride for oral suspension.

Colesevelam hydrochloride may decrease the absorption of fat-soluble vitamins A, D, E, and K. Patients with a susceptibility to deficiencies of vitamin K (e.g., patients on warfarin, patients with malabsorption syndromes) or other fat-soluble vitamins may be at increased risk when taking colesevelam hydrochloride.

Patients on oral vitamin supplementation should take their vitamins at least 4 hours prior to colesevelam hydrochloride [see Drug Interactions (7.1)].

Colesevelam hydrochloride can be dosed at the same time as a statin, or colesevelam hydrochloride and the statin can be dosed apart .Monitor lipid levels within 4 to 6 weeks after initiation of colesevelam hydrochloride.

Obtain lipid parameters, including triglyceride (TG) levels, before starting colesevelam hydrochloride. Colesevelam hydrochloride is contraindicated in patients with TG levels >500 mg/dL [see Contraindications (4)and Warnings and Precautions (5.1)] .

The recommended dosage of colesevelam hydrochloride for adults and for boys and postmenarchal girls aged 10 to 17 years with primary hyperlipidemia is 3.75 grams daily. The recommended dosage of colesevelam hydrochloride for adults with type 2 diabetes mellitus is 3.75 grams daily. Colesevelam hydrochloride should be taken as follows:

Table 4 includes a list of drugs that decrease exposure of the concomitant medication when administered concomitantly with colesevelam hydrochloride and instructions for preventing or managing them.

Tablets

Take 6 tablets once daily or 3 tablets twice daily. Due to tablet size, colesevelam hydrochloride for oral suspension is recommended for use in the pediatric population.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture. Brief exposure to 40°C (104°F) does not adversely affect colesevelam hydrochloride tablets.

Colesevelam hydrochloride is not absorbed and the risk of systemic toxicity is low. Excessive doses of colesevelam hydrochloride may cause more severe local gastrointestinal effects (e.g., constipation).

Colesevelam hydrochloride is a non-absorbed, polymeric, lipid-lowering and glucose-lowering agent for oral administration. Colesevelam hydrochloride is a high-capacity bile acid-binding molecule.

Colesevelam hydrochloride is poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and (6-bromohexyl)-trimethylammonium bromide. The chemical name (IUPAC) of colesevelam hydrochloride is allylamine polymer with 1-chloro-2,3-epoxypropane,[6-(allylamino)-hexyl] trimethylammonium chloride and N-allyldecylamine, hydrochloride. The chemical structure of colesevelam hydrochloride is represented by the following formula:

wherein (a) represents allyl amine monomer units that have not been alkylated by either of the 1-bromodecane or (6-bromohexyl)-trimethylammonium bromide alkylating agents or cross-linked by epichlorohydrin; (b) represents allyl amine units that have undergone cross-linking with epichlorohydrin; (c) represents allyl amine units that have been alkylated with a decyl group; (d) represents allyl amine units that have been alkylated with a (6-trimethylammonium) hexyl group, and m represents a number ≥100 to indicate an extended polymer network. A small amount of the amines are dialkylated and are not depicted in the formula above. No regular order of the groups is implied by the structure; cross-linking and alkylation are expected to occur randomly along the polymer chains. A large amount of the amines are protonated. The polymer is depicted in the hydrochloride form; a small amount of the halides are bromide. Colesevelam hydrochloride is hydrophilic and insoluble in water.

Colesevelam hydrochloride tablets are off-white, oval, film-coated, solid tablets each containing 625 mg colesevelam hydrochloride. In addition, each tablet contains the following inactive ingredients: magnesium stearate, microcrystalline cellulose, silicon dioxide, HPMC (hydroxypropyl methylcellulose), and acetylated monoglyceride. The tablets are imprinted using a water-soluble black ink (<5 calories per 6 tablets).

Colesevelam hydrochloride for oral suspension is a citrus-flavored, white to pale yellow powder containing yellow granules packaged in a packet containing 3.75 gram colesevelam hydrochloride. In addition, each packet contains the following inactive ingredients: lemon flavor, orange flavor, propylene glycol alginate, simethicone, aspartame, citric acid, medium chain triglycerides, and magnesium trisilicate (<5 calories per 3.75 gram single-dose packet). PHENYLKETONURICS: Colesevelam hydrochloride for oral suspension contains 27 mg phenylalanine per 3.75 gram dose.

Colesevelam hydrochloride is contraindicated in patients with:

• Serum TG concentrations >500 mg/dL [see Warnings and Precautions (5.1)]
• History of hypertriglyceridemia-induced pancreatitis [see Warnings and Precautions (5.1)]
• A history of bowel obstruction [see Warnings and Precautions (5.2)]

The following important adverse reactions are described below and elsewhere in the labeling:

• Hypertriglyceridemia and Pancreatitis [see Warnings and Precautions (5.1)]
• Gastrointestinal Obstruction [see Warnings and Precautions (5.2)]
• Vitamin K or Fat-Soluble Vitamin Deficiencies [see Warnings and Precautions (5.3)]

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 ( 7.1).

Concomitant use with colesevelam hydrochloride may increase the exposure of the following drugs:Metformin extended release. Monitor patients' glycemic control ( 7.2).

A maximum therapeutic response to the lipid-lowering effects of colesevelam hydrochloride was achieved within 2 weeks and was maintained during long-term therapy. In the diabetes clinical studies, a therapeutic response to colesevelam hydrochloride, as reflected by a reduction in HbA1c, was initially noted following 4-6 weeks of treatment and reached maximal or near-maximal effect after 12-18 weeks of treatment.

Colesevelam hydrochloride reduces gastrointestinal absorption of some drugs. Administer drugs with a known interaction at least 4 hours prior to colesevelam hydrochloride [see Drug Interactions (7)] .

Due to the potential for decreased absorption of other drugs that have not been tested for interaction, especially those with a narrow therapeutic index, consider administering at least 4 hours prior to colesevelam hydrochloride [see Clinical Pharmacology (12.3)].

• 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 Fredrickson Type I, III, IV, and V dyslipidemias.

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 ( 1.1).
• 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 ( 1.1).
• improve glycemic control in adults with type 2 diabetes mellitus ( 1.2).

Limitations of Use ( 1.3):

• Do not use for treatment of type 1 diabetes or for diabetic ketoacidosis.
• Not studied in Fredrickson Type I, III, IV, and V dyslipidemias

NDC 0713-0936-81

Colesevelam Hydrochloride

Tablets

625 mg

180 Tablets

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.

Colesevelam hydrochloride is indicated to reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia (HeFH) who are unable to reach LDL-C target levels despite an adequate trial of dietary therapy and lifestyle modification.

• 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 ( 5.1).
• 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 ( 5.2).
• Vitamin K or Fat-Soluble Vitamin Deficiencies: Colesevelam hydrochloride may decrease absorption of fat-soluble vitamins. Patients with a susceptibility to deficiencies of vitamin K (e.g., patients on warfarin, patients with malabsorption syndromes) or other fat-soluble vitamins may be at increased risk. Patients on oral vitamin supplementation should take their vitamins at least 4 hours prior to colesevelam hydrochloride ( 5.3).
• Drug Interactions:Due to the potential for decreased absorption of other drugs that have not been tested for interaction, consider administering at least 4 hours prior to colesevelam hydrochloride ( 5.4, 7, 12.3).
• Risks in Patients with Phenylketonuria (PKU):Phenylalanine can be harmful to patients with phenylketonuria. Colesevelam hydrochloride for oral suspension contains 27 mg phenylalanine per 3.75 gram packet ( 5.5, 11).

Colesevelam hydrochloride reduces total cholesterol (TC), LDL-C, apolipoprotein B (Apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) when administered alone or in combination with a statin in patients with primary hyperlipidemia.

Approximately 1600 patients were studied in 9 clinical trials with treatment durations ranging from 4 to 50 weeks. With the exception of one open-label, uncontrolled, long-term extension study, all studies were multicenter, randomized, double-blind, and placebo-controlled. A maximum therapeutic response to colesevelam hydrochloride was achieved within 2 weeks and was maintained during long-term therapy.

• Obtain lipid parameters, including serum triglyceride (TG) levels, before starting colesevelam hydrochloride ( 2.1).
• 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 ( 2.2, 2.4):

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 indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus .

• Tablets: 625 mg tablets are off-white, oval, film-coated and imprinted with "Sankyo" and "C01" on one side.
• For Oral Suspension: 3.75 gram packet containing a white to pale yellow powder with yellow granules.

Colesevelam hydrochloride has been studied as monotherapy and in combination with metformin, pioglitazone, sulfonylureas, and insulin. In these studies, colesevelam hydrochloride and placebo were administered either as 3 tablets twice daily with lunch and dinner or as 6 tablets with dinner alone.

The following additional adverse reactions have been identified during post-approval use of colesevelam hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse Reactions Resulting from Drug Interactions [see Drug Interactions (7)]: Increased seizure activity or decreased phenytoin levels in patients receiving phenytoin, reduced International Normalized Ratio (INR) in patients receiving warfarin therapy, and elevated thyroid-stimulating hormone (TSH) in patients receiving thyroid hormone replacement therapy

Gastrointestinal: Bowel obstruction (in patients with a history of bowel obstruction or resection), dysphagia or esophageal obstruction (occasionally requiring medical intervention), fecal impaction, pancreatitis, abdominal distension, exacerbation of hemorrhoids, and increased transaminases

Laboratory Abnormalities:Hypertriglyceridemia

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.

Postmarketing cases of bowel obstruction have occurred with colesevelam hydrochloride [see Adverse Reactions (6.2)] . 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. Colesevelam hydrochloride is contraindicated in patients with a history of bowel obstruction [see Contraindications (4)] . Instruct patients to promptly discontinue colesevelam hydrochloride and seek medical attention if severe abdominal pain or severe constipation occurs.

Because of the tablet size, colesevelam hydrochloride tablets can cause dysphagia or esophageal obstruction. For patients with difficulty swallowing tablets, use colesevelam hydrochloride for oral suspension.

Colesevelam hydrochloride 625 mg tablets are supplied as off-white, solid tablets imprinted with the word "Sankyo" and "C01" on one side and are available as follows:

• Bottles of 180 – NDC 0713-0936-81

Colesevelam hydrochloride 3.75 gram packets for oral suspension contain a white to pale yellow powder containing yellow granules and are available as follows:

• Cartons of 30 packets – NDC 0713-0935-30

Colesevelam hydrochloride, like other bile acid sequestrants, can increase serum TG concentrations. Hypertriglyceridemia can cause acute pancreatitis.

Colesevelam hydrochloride had effects on serum TG (median increase 5% compared to placebo) in trials of patients with primary hyperlipidemia.

In trials in patients with type 2 diabetes, greater increases in TG levels occurred when colesevelam hydrochloride was used as monotherapy (median increase 9.7% compared to placebo) and when colesevelam hydrochloride 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)].

Obtain lipid parameters, including TG levels, before starting colesevelam hydrochloride and periodically thereafter. Colesevelam hydrochloride is contraindicated in patients with TG levels >500 mg/dL or patients with a history of hypertriglyceridemia-induced pancreatitis [see Contraindications (4)] . Patients with TG levels greater than 300 mg/dL could have greater increases in serum TG levels with colesevelam hydrochloride and may require additional TG monitoring. Instruct patients to discontinue colesevelam hydrochloride and seek prompt medical attention if the symptoms of acute pancreatitis occur (e.g., severe abdominal pain with or without nausea and vomiting). Discontinue colesevelam hydrochloride if TG levels exceed 500 mg/dL [see Adverse Reactions (6.1)] .

TEAR HERE

No cutting required

Sugar-Free

This packet is contained within the

CARTON NDC 0713-0935-30

Rx only

Colesevelam

Hydrochloride

for Oral Suspension

3.75 g

Citrus Flavor

Single-Dose Packet

Each packet contains 3.75 grams of

colesevelam hydrochloride.

Keep Out of Reach of Children.

Package Not Child Resistant.

NDC 0713-0935-30

Rx only

30 packets

Colesevelam

Hydrochloride

for Oral Suspension

3.75 g

Each packet contains 3.75 grams of

colesevelam hydrochloride.

Dosing and use: see package insert.

Keep Out of Reach of Children.

Package Not Child Resistant.

Phenylalanine can be harmful to patients with PKU. Colesevelam hydrochloride for oral suspension contains phenylalanine, a component of aspartame. Each 3.75 gram packet contains 27 mg of phenylalanine. Before prescribing colesevelam hydrochloride for oral suspension to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including colesevelam hydrochloride for oral suspension.

Colesevelam hydrochloride may decrease the absorption of fat-soluble vitamins A, D, E, and K. Patients with a susceptibility to deficiencies of vitamin K (e.g., patients on warfarin, patients with malabsorption syndromes) or other fat-soluble vitamins may be at increased risk when taking colesevelam hydrochloride.

Patients on oral vitamin supplementation should take their vitamins at least 4 hours prior to colesevelam hydrochloride [see Drug Interactions (7.1)].

Colesevelam hydrochloride can be dosed at the same time as a statin, or colesevelam hydrochloride and the statin can be dosed apart .Monitor lipid levels within 4 to 6 weeks after initiation of colesevelam hydrochloride.

Obtain lipid parameters, including triglyceride (TG) levels, before starting colesevelam hydrochloride. Colesevelam hydrochloride is contraindicated in patients with TG levels >500 mg/dL [see Contraindications (4)and Warnings and Precautions (5.1)] .

The recommended dosage of colesevelam hydrochloride for adults and for boys and postmenarchal girls aged 10 to 17 years with primary hyperlipidemia is 3.75 grams daily. The recommended dosage of colesevelam hydrochloride for adults with type 2 diabetes mellitus is 3.75 grams daily. Colesevelam hydrochloride should be taken as follows:

Table 4 includes a list of drugs that decrease exposure of the concomitant medication when administered concomitantly with colesevelam hydrochloride and instructions for preventing or managing them.