Colesevelam Hydrochloride (Page 5 of 5)

Pediatric Therapy: The safety and efficacy of colesevelam hydrochloride in pediatric patients were evaluated in an 8-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study followed by an open-label phase, in 194 boys and post-menarchal girls 10 to 17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (heFH), taking a stable dose of an FDA-approved statin (with LDL-C >130 mg/dL) or naïve to lipid-lowering therapy (with LDL-C >160 mg/dL). This study had 3 periods: a single-blind, placebo stabilization period; an 8-week, randomized, double-blind, parallel-group, placebo-controlled treatment period; and an 18-week, open-label treatment period. Forty-seven (24%) patients were taking statins and 147 (76%) patients were statin-naïve at screening. The mean baseline LDL-C at Day 1 was approximately 199 mg/dL.

During the double-blind treatment period, patients were assigned randomly to treatment: colesevelam hydrochloride 3.8 g/day (n=64), colesevelam hydrochloride 1.9 g/day (n=65), or placebo (n=65). In total, 186 patients completed the double-blind treatment period. After 8 weeks of treatment, colesevelam hydrochloride 3.8 g/day significantly decreased plasma levels of LDL-C, non-HDL-C, TC, and Apo B and significantly increased HDL-C. A moderate, non-statistically significant increase in TG was observed versus placebo (Table 9).

Table 9 Response to Colesevelam Hydrochloride 3.8 g Compared to Placebo in Pediatric Patients 10 to 17 Years of Age – Mean Percent Change in Lipid Parameters from Baseline to Week 8

Treatment Difference	TC (N=128)	LDL-C (N=128)	Apo B (N=124)	HDL-C (N=128)	Non-HDL-C (N=128)	TG *(N=128)
* For triglycerides, median % change from baseline. Results were based on the ITT population with LOCF. † p ≤ 0.05 for lipid parameters compared to placebo. Values represent LS mean. Only patients with values at both study baseline and endpoint are included in this table. Study baseline was defined as the last value measured before or on Day 1 prior to the first dose of randomized study medication.
Colesevelam Hydrochloride 3.8 g vs. Placebo	-7 †	-13 †	-8 †	+6 †	-11 †	+5

During the open-label treatment period patients were treated with colesevelam hydrochloride 3.8 g/day. In total, 173 (89%) patients completed 26 weeks of treatment. Results at Week 26 were consistent with those at Week 8.

16 HOW SUPPLIED/STORAGE AND HANDLING

Colesevelam hydrochloride tablets, 625 mg, are supplied as off-white to pale yellow film-coated oval tablets, debossed with “L61” on one side and plain on the other side. Colesevelam hydrochloride tablets are available as follows:

• Bottles of 180 – NDC 42291-147-18

Storage: Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from moisture.

17 PATIENT COUNSELING INFORMATION

Dosing: Patients should be advised to take colesevelam hydrochloride tablets with a meal and liquid. Colesevelam hydrochloride can be taken as 6 tablets once daily or 3 tablets twice daily [see Dosage and Administration (2)].

Drug interactions: Drugs with a known interaction with colesevelam (e.g., cyclosporine, glimepiride, glipizide, glyburide, levothyroxine, olmesartan medoxomil, oral contraceptives) should be administered at least 4 hours prior to colesevelam hydrochloride. In an in vivo drug interaction study, there was no significant effect on the bioavailability of phenytoin; however, due to its narrow therapeutic index and post-marketing reports consistent with potential drug-drug interactions, phenytoin 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 blood levels of the coadministered drug. Patients receiving concomitant metformin ER and colesevelam should be monitored for clinical response as is usual for the use of anti-diabetes drugs [see Drug Interactions (7)].

Gastrointestinal: Colesevelam hydrochloride can cause constipation. Colesevelam hydrochloride is contraindicated in patients with a history of bowel obstruction. Colesevelam hydrochloride is not recommended in patients who may be at risk of bowel obstruction, including patients with gastroparesis, other gastrointestinal motility disorders, or a history of major gastrointestinal surgery. Patients should be instructed to consume a diet that promotes bowel regularity. Patients should be instructed 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 and should be used with caution in patients with dysphagia or swallowing disorders [see Warnings and Precautions (5.4)] .

Hypertriglyceridemia and pancreatitis: Patients should be instructed to discontinue colesevelam hydrochloride and seek prompt medical attention if the hallmark symptoms of acute pancreatitis occur (e.g., severe abdominal pain with or without nausea and vomiting) [see Warnings and Precautions (5.2)] .

17.1 Primary Hyperlipidemia

Patients should be advised to adhere to their National Cholesterol Education Program (NCEP)-recommended diet.

Hypertriglyceridemia and cardiovascular disease: Patients should be informed that colesevelam hydrochloride may increase serum triglyceride concentrations and that the long-term effect of hypertriglyceridemia on the risk of coronary artery disease is uncertain [see Warnings and Precautions (5.2)] .

Manufactured for:
AvKARE, Inc.
Pulaski, TN 38478

Mfg. Rev. 12/15
AV 06/18 (P)

PRINCIPAL DISPLAY PANEL — 180 Tablet Bottle Label

AvKARE _®

NDC 42291-147-18

Colesevelam
Hydrochloride
Tablets

625 mg

180 Tablets Rx Only
Each tablet contains: Active Ingredient:
Colesevelam hydrochloride 625 mg.

USUAL DOSAGE: See package insert for dosage
information.

Dispense in tightly-closed, light-resistant container as
defined in the USP, with child-resistant closure, as
required.

Store at 20°-25°C (68°-77°F) [See USP Controlled
Room Temperature].

Keep out of the reach of children.

Manufactured for:
AvKARE, Inc.
Pulaski, TN 38478

Mfg. Rev. 08/15 AV 06/18 (P)

COLESEVELAM HYDROCHLORIDE colesevelam hydrochloride tablet, coated

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:42291-147(NDC:0115-1320) Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength COLESEVELAM HYDROCHLORIDE (COLESEVELAM) COLESEVELAM HYDROCHLORIDE 625 mg

Inactive Ingredients Ingredient Name Strength SILICON DIOXIDE COPOVIDONE HYPROMELLOSE 2910 (6 MPA.S) HYPROMELLOSE 2910 (15 MPA.S) MAGNESIUM STEARATE CELLULOSE, MICROCRYSTALLINE POLYETHYLENE GLYCOL 6000 TALC

Product Characteristics Color white (off-white to pale yellow) Score no score Shape OVAL Size 8mm Flavor Imprint Code L61 Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:42291-147-18 180 TABLET, COATED in 1 BOTTLE None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA091600 06/18/2018

Labeler — AvKARE (796560394)

Revised: 01/2022 AvKARE