Olestyr: No FDA-Approved Medication with This Name
There is no FDA-approved medication called "Olestyr" in the current lipid-lowering medication armamentarium. The name appears to be a misspelling, possibly referring to a bile acid sequestrant such as cholestyramine (Questran), colestipol (Colestid), or colesevelam (Welchol) 1.
Bile Acid Sequestrants: Indications and Usage
If referring to bile acid sequestrants, the FDA-approved indications include:
Colesevelam:
- As an adjunct to diet and exercise to reduce LDL-C in adults with primary hyperlipidemia (monotherapy or with statins) 1
- To improve glycemic control in adults with type 2 diabetes mellitus 1
- To reduce LDL-C in boys and post-menarchal girls (10-17 years) with heterozygous familial hypercholesterolemia (HeFH) who have failed adequate diet therapy 1
Cholestyramine and Colestipol:
- As adjuncts to diet to decrease LDL-C in patients with primary hyperlipidemia 1
Mechanism of Action
Bile acid sequestrants work by:
- Binding bile acids in the intestine and preventing their reabsorption
- Decreasing the bile acid pool, which upregulates hepatic enzyme cholesterol 7-α-hydroxylase
- Increasing conversion of cholesterol to bile acids
- Creating increased demand for cholesterol in liver cells
- Increasing transcription of HMG-CoA reductase and increasing hepatic LDL receptors
- Resulting in increased clearance of LDL particles from blood 1
Efficacy in LDL-C Reduction
- Colesevelam: 15% reduction as monotherapy; additional 10-16% when combined with low-to-moderate intensity statins 1
- Cholestyramine: 10.4% reduction vs. placebo 1
- Colestipol: 16.3%, 22.8%, and 27.2% reductions at doses of 5g, 10g, and 15g respectively 1
Cardiovascular Outcomes
The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) demonstrated that cholestyramine reduced the risk of the primary endpoint (definite CHD death and/or definite nonfatal MI) by 19% compared to placebo in asymptomatic middle-aged men with primary hypercholesterolemia 1.
Important Contraindications
Bile acid sequestrants should not be used in patients with:
- Triglycerides >500 mg/dL (colesevelam)
- History of hypertriglyceridemia-induced pancreatitis (colesevelam)
- Bowel obstruction (colesevelam)
- Complete biliary obstruction (colestipol)
- History of serious hypersensitivity to these medications 1
Common Adverse Effects
- Constipation
- Dyspepsia
- Nausea 1
Important Drug Interactions
Bile acid sequestrants may decrease absorption of other medications. All other medications should be taken at least 4 hours before the bile acid sequestrant 1. Specific interactions include:
- Cyclosporin
- Oral contraceptives containing ethinyl estradiol and norethindrone
- Olmesartan
- Phenytoin
- Sulfonylureas
- Thyroid replacement therapy
- Warfarin 1
Clinical Considerations
- Bile acid sequestrants may increase triglycerides; monitor levels and discontinue if signs of acute pancreatitis occur
- May cause GI obstruction; avoid in patients with gastroparesis or other GI motility disorders
- May cause vitamin K or fat-soluble vitamin deficiencies; oral vitamins should be given at least 4 hours before administration
- Some products contain phenylalanine, which may be harmful to patients with phenylketonuria 1
- Considered safe to use during pregnancy and lactation 1
Placement in Therapy
In current lipid management guidelines, bile acid sequestrants are not first-line agents. The American College of Cardiology recommends ezetimibe as the first-line non-statin medication for dyslipidemia management due to its well-established safety profile, efficacy, and cardiovascular outcome benefits 2. Bile acid sequestrants may be considered if ezetimibe is not tolerated and triglycerides are low 2.
For patients requiring additional LDL-C lowering beyond statins, the stepwise approach typically involves:
- Maximally tolerated statin therapy
- Addition of ezetimibe
- Consideration of PCSK9 inhibitors if goals are still not met 2
Bile acid sequestrants are generally considered when other options have failed or are contraindicated, particularly given their pill burden, inconvenience in preparation, drug interactions, and GI side effects 1.