Effect of the Bile Acid Sequestrant Colesevelam on the Pharmacokinetics of Pioglitazone, Repaglinide, Estrogen Estradiol, Norethindrone, Levothyroxine, and Glyburide

Brown, Karen; Armstrong, Ingrid; Wang, Antonia; Walker, Joseph R.; Noveck, Robert J.; Swearingen, Dennis; Allison, Mark; Kissling, J.; Kisicki, James C.; Salazar, Daniel E.

doi:10.1177/0091270009349378

Cited by 22 publications

(17 citation statements)

References 27 publications

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“…Colesevelam has a low propensity for drug–drug interactions, and those that occur can typically be minimized by staggering drug administration by 4 h [60–63]. Notably, although drug–drug interactions with a number of lipid-lowering therapies (including simvastatin, fluvastatin, gemfibrozil, and ezetimibe) have been reported with the first-generation bile acid sequestrants [64–67], colesevelam has been shown to have no pharmacokinetic drug–drug interactions with lovastatin or fenofibrate [68, 69].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Role of Colesevelam in Combination Lipid-Lowering Therapy

Jones¹,

Nwose

2013

Am J Cardiovasc Drugs

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Hyperlipidemia is associated with an increased risk of cardiovascular events; reducing low-density lipoprotein cholesterol (LDL-C), the primary target for cholesterol-lowering therapy, lowers the risk for such events. Although bile acid sequestrants were the first class of drugs to show a mortality benefit related to LDL-C lowering, statins are now considered first-line pharmacological therapy for reducing LDL-C levels because of their potency and their remarkable record of successful outcomes studies. Nevertheless, a substantial proportion of patients do not achieve LDL-C goals with statin monotherapy. In addition, because of adverse effects (primarily myopathy), some patients may be unwilling to use or unable to tolerate statin therapy at all or may not tolerate a full therapeutic statin dose. Also, statins may increase risk of new-onset diabetes in patients at high risk for diabetes. Thus, there remains a need for other lipid-lowering drugs to be used in combination with or in place of statins. The purpose of this article is to review available data from the literature on the use of colesevelam, a second-generation bile acid sequestrant, in combination with other lipid-lowering agents. Colesevelam has been studied in combination with statins, niacin, fibrates, and ezetimibe (including some three-drug combinations). An additive reduction in LDL-C was seen with all combinations. Other observed effects of colesevelam in combination with other lipid-lowering drugs include reductions in apolipoprotein (apo) B (with statins, fibrates, ezetimibe, statin plus niacin, or statin plus ezetimibe) and high-sensitivity C-reactive protein (with statins), and increases in apo A-I (with statins, ezetimibe, or statins plus niacin). Triglyceride levels remained relatively unchanged when colesevelam was combined with statins, fibrates, ezetimibe, or statin plus ezetimibe, and decreased with the triple combination of colesevelam, statin, and niacin. Colesevelam offset the negative glycemic effects of statins and niacin in subjects with insulin resistance or impaired glucose tolerance. Colesevelam was generally well tolerated when added to other lipid-lowering therapies in clinical trials, with gastrointestinal effects such as constipation being the predominant adverse events. Since colesevelam is not absorbed and works primarily in the intestine, it has a low potential for systemic metabolic drug–drug interactions with other drugs. Colesevelam has been shown to not interact with the lipid-lowering drugs lovastatin and fenofibrate; where interaction may be anticipated, separating dosing times by 4 h reduces the impact of any interaction. Available data confirms that colesevelam has additive cholesterol-lowering effects when used in combination with other lipid-lowering therapies. Furthermore, in some patient populations, the additional glucose-lowering effect of colesevelam may be beneficial in offsetting hyperglycemic effects of other lipid-lowering drugs.

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Section: Safety and Tolerabilitymentioning

confidence: 99%

Role of Colesevelam in Combination Lipid-Lowering Therapy

Jones¹,

Nwose

2013

Am J Cardiovasc Drugs

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“…Because bile acid sequestrants are not absorbed, they do not cause many of the systemic toxicities that may occur with other classes of lipid-lowering drugs [51]. In addition, colesevelam has been shown to have a low propensity for drug–drug interactions [29, 52–55]. Where an interaction is apparent with a concomitant medication, the effect can typically be avoided by administration of colesevelam 4 h after the other drug [29].…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Colesevelam HCl in the Treatment of Elderly Patients

Gavin¹,

Jones

Ford

et al. 2014

Drugs Aging

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Background and objectivesColesevelam significantly lowers cholesterol in patients with hypercholesterolemia, and both cholesterol and hemoglobin A1C (A1C) in patients with type 2 diabetes mellitus (T2DM). The purpose of this post hoc analysis was to evaluate the efficacy and safety/tolerability of colesevelam in older (≥65 years) and younger (<65 years) adults.MethodsWe conducted post hoc analyses of pooled clinical trial data from seven phase II and III randomized, double-blind, placebo-controlled, primary hyperlipidemia and T2DM clinical trials. The hyperlipidemia safety/tolerability analysis included seven studies (≥65 years, n = 154; <65 years, n = 381); the efficacy analysis utilized one study with sufficient patients in both age groups for meaningful comparison. The T2DM analyses included four studies (safety/tolerability: ≥65 years, n = 249; <65 years, n = 880) or three studies (efficacy). In the hyperlipidemia studies, patients received colesevelam 1.5–4.5 g/day or placebo, alone or with a statin, for 4 weeks to 6 months. In the T2DM studies, colesevelam 3.75 g/day or placebo was added to existing antidiabetes therapies for 16 or 26 weeks. Low-density lipoprotein cholesterol (LDL-C), A1C, and adverse events were assessed.ResultsIn the hyperlipidemia analysis, colesevelam versus placebo produced similar mean reductions from baseline in LDL-C in older (−16.6 vs. +0.5 %) and younger (−13.7 vs. +0.4 %) patients. In the T2DM analysis, older and younger patients had similar reductions from baseline in A1C (treatment difference −0.59 and −0.54 %, respectively; both p < 0.001) and LDL-C (−14.7 and −15.5 %, respectively; both p < 0.001) with colesevelam. In both analyses, adverse event incidence was generally similar between subgroups. In the T2DM analysis, hypoglycemia was slightly more frequent with colesevelam versus placebo in older patients (5.8 vs. 2.3 %); no reports of hypoglycemia were considered serious adverse events.ConclusionsIn primary hyperlipidemia and in T2DM, colesevelam appeared to be generally as safe, well tolerated, and efficacious in patients aged ≥65 years as in those aged <65 years.

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“…33 Waiting 4 hours after ingestion of T 4 before giving bile acid sequestrants such as colesevelam may suffice to prevent the latter from interfering with the absorption of the former. 34 Ezetimibe does not interfere with T 4 absorption. 30 This list is not comprehensive.…”

Section: Medications and Absorption Of Tmentioning

confidence: 97%