Bile-Acid Sequestrant and Fibrate Therapy

Bile-acid sequestrants and fibrates are medications used to treat hyperlipidemia, or abnormally high levels of fats or lipids in the blood. Bile-acid sequestrants, like colesevelam, are used to reduce low-density lipoproteins, or LDLs, in patients with primary hypercholesterolemia. On the other hand, fibrates, also known as fibric acid derivatives, like gemfibrozil, are primarily used to lower triglyceride levels, but they can also lower total cholesterol and LDL levels while increasing high-density lipoproteins, or HDLs.

First, let’s focus on the bile-acid sequestrant, colesevelam, which is taken orally and isn’t absorbed by the GI tract. It works by binding with bile acid, preventing its reabsorption, and forming an insoluble complex that’s excreted in the stool. In response, the liver compensates by increasing bile salt production, which uses up a lot of cholesterol in its synthesis. Additionally, the liver increases uptake of LDLs, resulting in lowered LDL levels in both the liver and circulation. On the other hand, fibrates, like gemfibrozil, lower the triglyceride level by activating the peroxisome proliferator-activated receptor-alpha, or PPAR-α, receptor in the liver. This causes an increase in the production of lipoprotein lipase, an enzyme that increases lipolysis, reduces hepatic triglyceride production, and increases HDL formation.

Okay, so common side effects of both bile acid sequestrants and fibrates include GI disturbances, such as constipation, nausea, vomiting, dyspepsia, bloating, and abdominal pain. However, as opposed to other bile acid sequestrants, colesevelam is associated with fewer of these side effects. Colesevelam can also decrease the absorption of fat-soluble vitamins, such as A, D, E, and K; which can increase the risk of bleeding due to decreased synthesis of vitamin K-dependent clotting factors. Side effects specific to gemfibrozil include increased risk of gallstone formation, liver injury, and myopathy.

As far as contraindications go, colesevelam shouldn’t be used in patients with biliary or bowel obstruction. And since lipids and fat-soluble vitamins are needed for normal fetal development, colesevelam should be used with caution during pregnancy. On the other hand, gemfibrozil is contraindicated in patients with preexisting gallbladder disease, severe renal or hepatic dysfunction, and primary biliary cirrhosis. In terms of interactions, colesevelam can bind with other medications, like warfarin, digoxin, and thiazide diuretics, decreasing their effectiveness. Like colesevelam, gemfibrozil also interacts with warfarin, but by increasing its anticoagulant effects instead. Gemfibrozil also shouldn’t be given along with HMG-CoA reductase inhibitors, or statins, as they can further increase the risk of myopathy.