Overview of Fibric Acid Derivatives
February 15, 2021
Fibrates for High Triglycerides… not so fast
ASCVD: Elevated fasting plasma triglycerides levels are associated with atherosclerotic cardiovascular disease (ASCVD) burden and events such as myocardial infarction and stroke. Triglycerides over 150mg/dl seems to increase the risk of ASCVD. Elevated triglycerides are also associated with insulin resistance, metabolic syndrome, platelet aggregation and low HDL. Lowering TG’s has not been proven to reduce ASCVD events.
Acute pancreatitis: The risk for acute pancreatitis rises when serum TG levels exceed 500 mg/dL. The risk of developing acute pancreatitis is approximately 5 percent when TG’s exceed 1000mg/dl and up to 20 percent with TGs exceed 2000 mg/dL.
Medications that can exacerbate hypertriglyceridemia:
- Oral estrogens
- Bile-acid sequestrants (Cholestyramine, Colestipol, Colesevelam)
- Antiretroviral regimens, especially for HIV (especially Protease inhibitors)
- Second-generation antipsychotic medications such as clozapine (Clozaril) and olanzapine (Zyprexa)
- Nonselective beta blockers (propranolol)
- Thiazide Diuretics
- Increased consumption of alcohol, sugar-containing beverages and simple carbohydrates
FIBRIC ACID DERIVITIVES
Mechanism of Action: Bind to and stimulate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor which increases lipoprotein lipase activity, which hydrolyzes triglycerides from VLDL. Other effects include decreased hepatic cholesterol synthesis, and increased cholesterol secretion in the bile
Indication: 20 to 50% reduction in triglycerides
Warnings/ Precautions/Adverse effects
- Caution if combined with statins (watch CK, rhabdomyolysis)
- Take with food to minimize GI upset
- May increase gallstones – don’t give if patient has gallbladder disease.
Drug Interactions: Fibrates will increase warfarin effect- reduce warfarin dose by 30%
Patient Education: Take with food to minimize GI effects
Products of this Class (Fibrates)
- Gemfibrozil (Lopid®)
- 600mg tablets
- Dosage: 1 tablet BID
- Prescriber note: Avoid combining Gemfibrozil with statins CONTRAINDICATED.
- Fenofibrate (Tricor®)
- Tablets 48mg and 145mg (new formulations)
- Dosage: 1 tablet daily
- Other fenofibrate formulations: 54mg, 67mg, 134mg, 150mg, 160mg, 200mg
Fibric acid derivatives have fallen out of favor.
NOTE: Statins typically lower TG levels by 5 to 15 percent; however, high-intensity statin therapy can lower TGs by 25 to 30 percent. Most clinicians will increase the statin dose rather than add a fibrate. Fibrates, when combined with statins did not lower risk of non-fatal MI, non-fatal stroke, or CV death.
Gemfibrozil is the only fibrate with demonstrated beneficial effects on cardiovascular outcomes, but its use with statins can increase the risk of myopathy and is not recommended. Fenofibrate is not proven, gemfibrozil with statins causes high risk of myopathy and is not recommended.
For most of our patients elevated triglycerides seem to be directly connected to their poor diet of refined carbohydrates. Pizza, pasta, bread, sugar drinks, cookies, donuts, virtually anything that tastes good can drive up triglycerides. Fibrates are of not much value.
Treatment of elevated triglycerides is better left to the dietician, rather than reaching for the fibrates! Diet and exercise are the cornerstone for hyperlipidemia, cardiovascular disease, and diabetes.
Tricor was first introduced in 1993 (67mg, 134mg, 200mg), and reformulated in 2001 (54mg and 160mg), and again in 2004 (48mg and 145mg), just to protect the patent. To follow up, they introduced Trilipix (fenofibric acid) in 2008, which was their last attempt to breathe life into this product. It bombed.
Have a Great Day on the Bench!