Bile Acid Sequestrants and Fibrates: Available Options
Bile Acid Sequestrants
Over-the-Counter Options
No bile acid sequestrants are available over-the-counter. All bile acid sequestrants require a prescription in the United States 1.
Prescription Options
Three bile acid sequestrants are FDA-approved and available by prescription:
Colesevelam (Welchol): The most modern and best-tolerated option, available as tablets (625 mg) or oral suspension (3.75 g packets). Dosing is 6 tablets once daily or 3 tablets twice daily with meals, or one 3.75 g packet daily 2, 1. Colesevelam provides 15% LDL-C reduction as monotherapy and an additional 10-16% reduction when combined with statins 2.
Cholestyramine (Questran): The original bile acid sequestrant, dosed at 8-16 g/day orally divided into 2 doses, providing approximately 10.4% LDL-C reduction versus placebo 2.
Colestipol (Colestid): Available in granule and tablet forms, dosed at 2-16 g/day orally given once or in divided doses. In dose-ranging studies, 15 g daily resulted in 27.2% LDL-C reduction 2.
Key Prescribing Considerations for Bile Acid Sequestrants
Colesevelam has significant advantages over older agents: better tolerability, fewer gastrointestinal side effects, and no gritty texture 3. The older sequestrants (cholestyramine and colestipol) are bulky, unpalatable resins that cause significant constipation and bloating 4.
Critical contraindications: Bile acid sequestrants are contraindicated when triglycerides exceed 500 mg/dL (colesevelam) or 200 mg/dL (general caution for all sequestrants), as they can worsen hypertriglyceridemia and precipitate pancreatitis 2, 1. They are also contraindicated in bowel obstruction and should be avoided in gastroparesis or major GI motility disorders 2, 1.
Drug interactions are significant: Bile acid sequestrants can interfere with absorption of many medications including warfarin, thyroid hormones, and phenytoin. Administer other medications at least 4 hours before the sequestrant 2, 1.
Fibrates
Over-the-Counter Options
No fibrates are available over-the-counter. All fibrate medications require a prescription 5.
Prescription Options
Two fibrates are commonly used in the United States:
Fenofibrate (Tricor, Trilipix, generics): The preferred fibrate due to superior safety profile when combined with statins. Multiple formulations exist with varying bioavailability. Standard dosing is 54-160 mg daily with meals, adjusted for renal function 2, 6, 5. Fenofibrate reduces triglycerides by 30-50% and is FDA-approved for mixed dyslipidemia and severe hypertriglyceridemia 6, 5.
Gemfibrozil (Lopid): Older fibrate that should generally be avoided, especially when combining with statins, due to significantly higher myopathy risk. Gemfibrozil inhibits statin glucuronidation, unlike fenofibrate 2.
Key Prescribing Considerations for Fibrates
Fenofibrate is strongly preferred over gemfibrozil when combination therapy with statins is needed, as it has a much better safety profile and does not inhibit statin metabolism 2, 6.
Primary indication: Fibrates are first-line therapy for severe hypertriglyceridemia (≥500 mg/dL) to prevent acute pancreatitis, initiated before statin therapy at this threshold 2, 6. For moderate hypertriglyceridemia (200-499 mg/dL), fibrates are considered only after optimizing statin therapy and lifestyle modifications for 3 months 6, 7.
Renal dosing is critical: Fenofibrate must be dose-adjusted for renal impairment. Start at 54 mg daily and do not exceed this dose if eGFR is 30-59 mL/min/1.73 m². Fenofibrate is contraindicated if eGFR <30 mL/min/1.73 m² 7, 5.
Combination therapy risks: When combining fenofibrate with statins, use lower statin doses (e.g., atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease 2, 6. Monitor creatine kinase levels at baseline and during therapy 2, 6.
Cardiovascular outcomes: The ACCORD trial showed no cardiovascular benefit from adding fenofibrate to statins in diabetic patients, though fibrates remain indicated for pancreatitis prevention at triglyceride levels ≥500 mg/dL 6, 7.
Clinical Algorithm for Selection
For elevated LDL-C with normal triglycerides (<200 mg/dL): Consider bile acid sequestrants as add-on therapy to statins, with colesevelam as the preferred agent due to superior tolerability 2, 3.
For triglycerides 200-499 mg/dL: Optimize statin therapy first. If triglycerides remain elevated after 3 months of lifestyle modifications, consider prescription omega-3 fatty acids (icosapent ethyl) before fibrates 6, 7.
For triglycerides ≥500 mg/dL: Initiate fenofibrate immediately (54-160 mg daily) to prevent acute pancreatitis, before addressing LDL-C with statins 6, 7, 5.
Never use bile acid sequestrants when triglycerides exceed 200 mg/dL, as they worsen hypertriglyceridemia 2, 6.