Welchol Information
Welchol (Colesevelam) Indications And Usage
Welchol (Colesevelam) 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 an hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin).
Welchol (Colesevelam) is indicated as monotherapy or in combination with a statin to reduce LDL-C levels in boys and postmenarchal 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
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 .
In patients with coronary heart disease (CHD) or CHD risk equivalents such as diabetes mellitus, LDL-C treatment goals are 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.
Welchol (Colesevelam) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus .
Diabetes mellitus is considered a CHD risk equivalent. In addition to glycemic control, intensive lipid control is warranted .
Welchol (Colesevelam) Dosage And Administration
The recommended dose of Welchol (Colesevelam) Tablets in adults, whether used as monotherapy or in combination with a statin, is 6 tablets once daily or 3 tablets twice daily. Welchol (Colesevelam) Tablets should be taken with a meal and liquid.
The recommended dose of Welchol (Colesevelam) for Oral Suspension, in adults and children 10 to 17 years of age, is one 3.75 gram packet once daily or one 1.875 gram packet twice daily. To prepare, empty the entire contents of one packet into a glass or cup. Add ½ to 1 cup (4 to 8 ounces) of water. Stir well and drink. Welchol (Colesevelam) for Oral Suspension should be taken with meals. To avoid esophageal distress, Welchol (Colesevelam) for Oral Suspension should not be taken in its dry form. Due to tablet size, it is recommended that any patient who has difficulty swallowing tablets use Welchol (Colesevelam) for Oral Suspension.
Welchol (Colesevelam) can be dosed at the same time as a statin or the two drugs can be dosed apart .
After initiation of Welchol (Colesevelam) , lipid levels should be analyzed within 4 to 6 weeks.
The recommended dose of Welchol (Colesevelam) Tablets is 6 tablets once daily or 3 tablets twice daily. Welchol (Colesevelam) should be taken with a meal and liquid.
The recommended dose of Welchol (Colesevelam) for Oral Suspension is one 3.75 gram packet once daily or one 1.875 gram packet twice daily. To prepare, empty the entire contents of one packet into a glass or cup. Add ½ to 1 cup (4 to 8 ounces) of water. Stir well and drink. Welchol (Colesevelam) for Oral Suspension should be taken with meals. To avoid esophageal distress, Welchol (Colesevelam) for Oral Suspension should not be taken in its dry form.
Welchol (Colesevelam) Contraindications
Welchol (Colesevelam) is contraindicated in patients with
Welchol (Colesevelam) Warnings And Precautions
Welchol (Colesevelam) , like other bile acid sequestrants, can increase serum TG concentrations.
Welchol (Colesevelam) had small effects on serum TG (median increase 5% compared to placebo) in trials of patients with primary hyperlipidemia .
In clinical trials in patients with type 2 diabetes, greater increases in TG levels occurred when Welchol (Colesevelam) was used in combination with sulfonylureas (median increase 18% compared to placebo in combination with sulfonylureas) and when Welchol (Colesevelam) was used in combination with insulin (median increase 22% compared to placebo in combination with insulin) . 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 (Colesevelam) on LDL-C levels may be attenuated by Welchol (Colesevelam) ’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 (Colesevelam) clinical trials had baseline TG 500 mg/dL . Lipid parameters, including TG levels and non-HDL-C, should be obtained before starting Welchol (Colesevelam) and periodically thereafter. Welchol (Colesevelam) should be discontinued if TG levels exceed 500 mg/dL or if the patient develops hypertriglyceridemia-induced pancreatitis .
Welchol (Colesevelam) for Oral Suspension contains 24 mg phenylalanine per 1.875 gram packet and 48 mg phenylalanine per 3.75 gram packet .
Welchol (Colesevelam) Adverse Reactions
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.
In the lipid-lowering trials, 807 adult patients received at least one dose of Welchol (Colesevelam) (total exposure 199 patient-years). In the type 2 diabetes trials, 566 patients received at least one dose of Welchol (Colesevelam) (total exposure 209 patient-years).
In clinical trials for the reduction of LDL-C, 68% of patients receiving Welchol (Colesevelam) vs. 64% of patients receiving placebo reported an adverse reaction. In clinical trials of type 2 diabetes, 60% of patients receiving Welchol (Colesevelam) vs. 56% of patients receiving placebo reported an adverse reaction.
Welchol (Colesevelam) Drug Interactions
Table 4 lists the drugs that have been tested in binding or drug interaction studies with colesevelam and/or drugs with postmarketing reports consistent with potential drug-drug interactions. Orally administered 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 (Colesevelam) . Alternatively, the physician should monitor drug levels of the co-administered drug.
In an drug interaction study, Welchol (Colesevelam) and warfarin coadministration had no effect on warfarin drug levels. This study did not assess the effect of Welchol (Colesevelam) and warfarin coadministration on INR. In postmarketing reports, concomitant use of Welchol (Colesevelam) and warfarin has been associated with reduced INR. Therefore, in patients on warfarin therapy, the INR should be monitored before initiating Welchol (Colesevelam) and frequently enough during early Welchol (Colesevelam) therapy to ensure that no significant alteration in INR occurs. Once the INR is stable, continue to monitor the INR at intervals usually recommended for patients on warfarin.
Welchol (Colesevelam) Use In Specific Populations
The safety and effectiveness of Welchol (Colesevelam) as monotherapy or in combination with a statin were evaluated in children, 10 to 17 years of age with heFH . The adverse reaction profile was similar to that of patients treated with placebo. In this limited controlled study, there were no significant effects on growth, sexual maturation, fat-soluble vitamin levels or clotting factors in the adolescent boys or girls relative to placebo [].
Due to tablet size, Welchol (Colesevelam) for Oral Suspension is recommended for use in the pediatric population. Dose adjustments are not required when Welchol (Colesevelam) is administered to children 10 to 17 years of age.
Welchol (Colesevelam) has not been studied in children younger than 10 years of age or in pre-menarchal girls.
Welchol (Colesevelam) Overdosage
Doses of Welchol (Colesevelam) in excess of 4.5 g/day have not been tested. Because Welchol (Colesevelam) is not absorbed, the risk of systemic toxicity is low. However, excessive doses of Welchol (Colesevelam) may cause more severe local gastrointestinal effects (e.g., constipation) than recommended doses.
Welchol (Colesevelam) Description
Welchol (Colesevelam) (colesevelam hydrochloride) is a non-absorbed, polymeric, lipid-lowering and glucose-lowering agent intended 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 crosslinking 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.
Welchol (Colesevelam) Tablets are an off-white, oval, film-coated, solid tablet 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.
Welchol (Colesevelam) for Oral Suspension is a citrus-flavored, white to pale yellow powder containing yellow granules packaged in single-dose packets containing either 1.875 gram or 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.
Welchol (Colesevelam) Clinical Studies
Welchol (Colesevelam) reduces TC, LDL-C, apolipoprotein B (Apo B), and 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 Welchol (Colesevelam) was achieved within 2 weeks and was maintained during long-term therapy.
Welchol (Colesevelam) has been studied in combination with metformin, sulfonylureas, and insulin. Welchol (Colesevelam) has not been studied as monotherapy.
The efficacy of Welchol (Colesevelam) 3.8 g/day in patients with type 2 diabetes mellitus was evaluated in 3 double-blind, placebo-controlled add-on therapy trials involving a total of 1018 patients with baseline A1C 7.5-9.5%. Patients were enrolled and maintained on their pre-existing, stable, background anti-diabetic regimen. Welchol (Colesevelam) and placebo were administered either as 3 tablets twice daily with lunch and dinner or as 6 tablets with dinner alone.
In these studies, the overall mean age was 57 years (range 24-81 years), 47% were women, and 59% of the patients were Caucasian, 23% were Hispanic, 14% were Black, 3% were Asian, and 1% were of other racial groups. Statin use at baseline was reported in 42% of the Welchol (Colesevelam) -treated patients and 50% of the placebo-treated patients.
In all 3 pivotal add-on therapy trials, treatment with Welchol (Colesevelam) resulted in a statistically significant reduction in A1C of 0.5% compared to placebo. Similar placebo-corrected reductions in A1C occurred in patients who received Welchol (Colesevelam) in combination with metformin, sulfonylurea, or insulin monotherapy or combinations of these therapies with other anti-diabetic agents. In the metformin and sulfonylurea trials, treatment with Welchol (Colesevelam) also resulted in statistically significant reductions in fasting plasma glucose (FPG) of 14 mg/dL compared to placebo.
Welchol (Colesevelam) had consistent effects on A1C across subgroups of age, gender, race, body mass index, and baseline A1C. Welchol (Colesevelam) ’s effects on A1C were also similar for the two dosing regimens (3 tablets with lunch and with dinner or 6 tablets with dinner alone).
The mean baseline LDL-C was 104 mg/dL in the metformin study (range 32-214 mg/dL), 106 mg/dL in the sulfonylurea study (range 41-264 mg/dL), and 102 mg/dL in the insulin study (range 35-204 mg/dL). In these trials, Welchol (Colesevelam) treatment was associated with a 12% to 16% reduction in LDL-C levels. The percentage decreases in LDL-C were of similar magnitude to those observed in patients with primary hyperlipidemia. Welchol (Colesevelam) treatment was associated with statistically significant increases in TG levels in the studies of patients on insulin and patients on a sulfonylurea, but not in the study of patients on metformin. The clinical significance of these increases is unknown. Welchol (Colesevelam) is contraindicated in patients with TG levels > 500 mg/dL and periodic monitoring of lipid parameters including TG and non-HDL-C levels is recommended .
Body weight did not significantly increase from baseline with Welchol (Colesevelam) therapy, compared with placebo, in any of the 3 pivotal clinical studies.
Welchol (Colesevelam) How Supplied/storage And Handling
Welchol (Colesevelam) (colesevelam hydrochloride) Tablets, 625 mg, are supplied as an off-white, solid tablet imprinted with the word “Sankyo” and “C01” on one side. Welchol (Colesevelam) tablets are available as follows: • Bottles of 180 - NDC 21695-781-78
Welchol (Colesevelam) Principal Display Panel
Welchol (Colesevelam) Principal Display Panel
