21.3: Bile Acid Sequestrants, Fibrates, and Niacin
By the end of this section, you should be able to:
- 21.3.1 Identify the characteristics of bile acid sequestrant, fibrates, and niacin drugs used to lower lipid levels.
- 21.3.2 Explain the indications, action, adverse reactions, and interactions of bile acid sequestrant, fibrates, and niacin drugs used to lower lipid levels.
- 21.3.3 Describe nursing implications of bile acid sequestrant, fibrates, and niacin drugs used to lower lipid levels.
- 21.3.4 Explain the client education related to bile acid sequestrant, fibrates, and niacin drugs used to lower lipid levels.
Bile acid sequestrants, fibrates, and niacin vary in their mechanism, therapeutic effect, and side effect profile. Table 21.6 lists common bile acid sequestrants, fibrates, and niacin and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
|
Cholestyramine
( Questran ) |
Hyperlipidemia: Initiate at 4 g orally 1–2 times daily; increase gradually to 8–16 g orally in 2 divided doses; maximum dose 24 g/day. |
|
Cholesevelam
( Welchol ) |
Hyperlipidemia: 3.75 g/day orally in 1–2 divided doses. |
|
Colestipol
( Colestid ) |
Hyperlipidemia (tablets): Initial dose 2 g orally 1–2 times daily; increase by 2 g orally 1–2 times daily at 1–2-month intervals; maintenance dose is 2–16 g orally once daily or in divided doses. |
|
Fenofibrate
( Tricor ) |
Hypertriglyceridemia:
48–145 mg orally once daily; maximum dose is 145 mg.
Primary hypercholesterolemia or mixed dyslipidemia: Initial dose 145 mg once daily. |
|
Gemfibrozil
( Lopid ) |
Hypertriglyceridemia: 1200 mg administered orally in 2 divided doses 30 min before the morning and evening meals. |
| Niacin | Hyperlipidemia or hypertriglyceridemia (niacin extended-release prescription product): Initial dose 500 mg orally at bedtime after a low-fat snack; increase by no more than 500 mg in any 4-week period; maintenance dose is 1000–2000 mg once daily at bedtime. |
Bile Acid Sequestrants
Bile acid sequestrants are a class of drugs that lower cholesterol. Bile acids are made from cholesterol and are released from the small intestine to aid in fat digestion after the individual consumes food. The majority of bile acids are reabsorbed back into the body after use. Bile acid sequestrants work by binding to bile acids in the intestine, which reduces their absorption and decreases the amount of bile acids available in the body. The body compensates for this by producing more bile acids from cholesterol, effectively decreasing the amount of cholesterol that remains.
Bile acid sequestrants are often used as second-line therapy for hypercholesterolemia if clients do not achieve sufficient goals using first-line therapy or if they are intolerant to first-line therapy. Bile acid sequestrants can be expected to lower the LDL-cholesterol levels by 15%–30% (Grundy et al., 2019). Response to therapy is monitored by obtaining LDL-cholesterol levels. These drugs are orally administered and are not absorbed into the systemic circulation; therefore, they are best taken with meals so that they will encounter the bile acids upon secretion. However, their use is limited by frequency of dosing, an unfavorable gastrointestinal adverse effect profile, and their propensity for interaction with other drugs, which necessitates coordination of administration. Also, outcomes data in cardiovascular disease are lacking when used in combination with statins, the first-line therapy for hypercholesterolemia and cardiovascular risk reduction.
Three bile acid sequestrants are used for treating hyperlipidemia. The drugs have few distinguishing factors beyond the class effects listed here. Some of the differentiators are the available dosage forms (tablets, powder), administration instructions, and FDA-approved indications. These are summarized in Table 21.7; however, it is always best to check the specific product labeling for administration instructions.
| Drug | FDA-Approved Indications | Available Dosage Forms | Special Administration Instructions |
|---|---|---|---|
| Cholestyramine |
|
|
Oral powder:
|
| Colesevelam |
|
|
Oral powder:
|
| Colestipol |
|
|
Oral powder:
|
Fibrates
Fibrates are a group of oral drugs that are used primarily to treat hypertriglyceridemia. They include fenofibric acid, fenofibrate, and gemfibrozil. They work by activating peroxisome proliferator-activated receptors. The primary result of this activation is lower triglyceride levels via increased expression of lipoprotein lipase, an enzyme that breaks down triglycerides. Fibrates also lead to increased HDL-cholesterol and mildly lower LDL-cholesterol levels; however, they are not typically recommended for those uses (Grundy et al., 2019). Adverse effects of fibrates include increased serum transaminase, creatine phosphokinase (CPK), and creatinine levels; myopathy; cholelithiasis; and venous thrombosis.
Fenofibric Acid Derivatives
Fenofibric acid is an active drug that directly stimulates peroxisome proliferator-activated receptors as described above. It is available in the active form under the brand name Fibricor and as generic drugs. An inactive form called fenofibrate is also available; this form converts to fenofibric acid in the body after ingestion. Some of the available dosage forms of fenofibrate are Antara, Lipofen, Fenoglide, Tricor, Trilipix (choline fenofibrate), and their respective generic formulations. The various fenofibrate dosage forms are not bioequivalent and cannot be substituted for each other or for fenofibric acid on a milligram-per-milligram basis; they use different types of medication delivery technology to ensure absorption, including micronized particles, nanocrystals, and different salt forms.
Table 21.8 is a drug prototype table for fenofibric acid derivatives featuring fenofibrate. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Fibric acid Mechanism of Action Activates peroxisome proliferator-activated receptors to increase breakdown of triglycerides |
Drug Dosage
Primary hypercholesterolemia or mixed dyslipidemia: Initial dose 145 mg orally once daily; maximum dose 145 mg once daily. Severe hypertriglyceridemia: Initial dose 48–145 mg once daily; maximum dose 145 mg once daily. |
|
Indications
Primary hyperlipidemia or mixed dyslipidemia Severe hypertriglyceridemia Therapeutic Effects Reduces LDL-cholesterol, total cholesterol, triglycerides, and apolipoprotein B; increases HDL-cholesterol |
Drug Interactions
Warfarin Immunosuppressants Bile acid sequestrants Colchicine Statins Food Interactions No significant interactions |
|
Adverse Effects
Abnormal liver function tests, including increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase (CPK) levels Rhinitis |
Contraindications
Severe renal dysfunction, including dialysis Active liver disease Gallbladder disease Hypersensitivity Lactation Caution: Hepatotoxicity Myopathy and rhabdomyolysis Increases in serum creatinine Cholelithiasis |
Gemfibrozil
Gemfibrozil is another fibrate approved for the treatment of hypertriglyceridemia and for primary prevention of CAD in clients who have failed to respond to lifestyle changes and other pharmacologic therapies. Gemfibrozil is generally administered orally, twice daily, 30 minutes before breakfast and dinner. The most common adverse events are dyspepsia, abdominal pain, and diarrhea. Less commonly, abnormal liver function tests and worsening renal function in those with baseline dysfunction have been reported. It is contraindicated in clients with severe hepatic or renal disease, preexisting gallbladder disease, or hypersensitivity to gemfibrozil.
Gemfibrozil is associated with several notable drug interactions. The concomitant use of gemfibrozil and rosuvastatin or simvastatin is contraindicated because of the risk of myopathy and rhabdomyolysis. If the client needs to take both a fibrate and a statin, it is safer to use a fenofibric acid derivative. Similarly, a client taking gemfibrozil with colchicine should be monitored for the same concerns of myopathy and rhabdomyolysis. Concomitant use with warfarin places the client at risk for bleeding, so frequent monitoring of the international normalized ratio is recommended until stabilization.
Safety Alert
Gemfibrozil
The nurse should clarify any medication orders that use abbreviations. For example, gemfibrozil could be abbreviated as “gem.” This could be confused with gemcitabine , a chemotherapy agent, with severe consequences. Learn more about error-prone abbreviations like this one by visiting the website for the Institute for Safe Medication Practices .
Niacin
Niacin (vitamin B 3 ) is a water-soluble vitamin. The chemical name for niacin is nicotinic acid. It is approved for treatment of hyperlipidemia, dyslipidemia, and hypertriglyceridemia; for secondary prevention of myocardial infarction; and, in combination with a bile acid sequestrant, for slowing the progression or promoting the regression of atherosclerotic disease. The specific mechanism of action of niacin in dyslipidemia is not well understood. It may increase the activity of lipoprotein lipase, the main enzyme that is affected by fibrates, or it may increase the rate of removal from plasma and decrease the rate of synthesis of LDL-cholesterol. The therapeutic effect in dyslipidemia is a reduction in triglyceride, LDL-cholesterol, and total cholesterol levels as well as an increase in HDL-cholesterol levels.
Niacin is available in various dosage forms. Many are considered dietary supplements and thus are not regulated by the FDA. Some of these dietary supplements are marketed as “flush-free” niacin; however, these flush-free versions have been shown to contain no free nicotinic acid and should not be used to treat dyslipidemia (National Institutes of Health, 2022). Prescription niacin products include extended-release and immediate-release formulations. Nurses should be aware that the various niacin preparations are not interchangeable on a milligram-per-milligram basis.
Adverse Effects and Contraindications
Bile acid sequestrants. Because these drugs are not absorbed into the systemic circulation, systemic adverse effects are limited; side effects from bile acid sequestrants are generally related to their effect on the gastrointestinal system. Constipation is the most common one; it can be severe and can aggravate hemorrhoids. Clients can minimize constipation by starting doses cautiously, taking one per day. It can also be managed with increased fluids and dietary fiber and, if needed, a stool softener. Other gastrointestinal adverse effects include abdominal pain, heartburn, loss of appetite, indigestion, diarrhea, and upset stomach.
Bile acid sequestrants also can cause an increase in triglyceride levels, which is typically mild. However, in clients with a triglyceride level of 300 mg/dL or higher at baseline, hypertriglyceridemia can be severe. With long-term therapy of high doses, absorption of some fat-soluble nutrients may be decreased, and supplementation of vitamins A, D, E, and K may be needed. In extreme cases, bleeding can occur due to an induced deficiency of vitamin K, which is needed for the synthesis of clotting factors. Additionally, bile acid sequestrants can interfere with the absorption of some drugs. Because of this, it is recommended that clients take other drugs at least 1 hour before or 3–4 hours after taking a bile acid sequestrant (Grundy et al., 2019).
Because of the high incidence of constipation, bile acid sequestrants are contraindicated in clients with a history of bowel obstruction. Because these drugs can increase triglycerides, they also are contraindicated in clients who have baseline hypertriglyceridemia or a history of pancreatitis due to hypertriglyceridemia.
Fibrates. The most common adverse effects of fibrates are elevated liver enzymes, increases in serum creatinine, and myopathy, especially when fibrates are combined with statin medications. They should not be used in clients who have active liver disease, gallbladder disease, severe renal dysfunction, or hypersensitivity (Singh & Correa, 2023).
Niacin. The most limiting adverse effect of niacin is flushing, which is most prominent in the immediate-release preparations. This occurs because niacin increases prostaglandins in capillaries, leading to cutaneous vasodilation. It can be managed by slowing down the niacin absorption rate by using a slower-release (extended-release) version or by administering a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin 30 minutes before niacin administration (National Institutes of Health, 2022). Clients taking niacin can minimize flushing by avoiding hot drinks and alcoholic beverages. Significant adverse effects include hepatotoxicity, insulin resistance, hyperglycemia, and hyperuricemia (National Institutes of Health, 2022).
Niacin is contraindicated in clients with active liver disease, unexplained or persistent elevations in hepatic transaminase levels, active peptic ulcer disease, arterial bleeding, or hypersensitivity to niacin or components of the formulation.
Nursing Implications
The nurse should do the following for clients taking bile acid sequestrants:
- Monitor for constipation and instruct client about appropriate management (increase fluids and dietary fiber and, if needed, take a stool softener).
- Administer other drugs at least 1 hour before or 3–4 hours after bile acid sequestrant administration.
- Mix powder dosage forms with fluid as appropriate.
- Monitor for deficiency of fat-soluble nutrients and recommend supplementation when needed.
- Administer with meals as directed by the health care provider.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
The nurse should do the following for clients taking fibrates:
- Obtain an accurate home medication list to assess for drug interactions.
- Avoid direct substitution of different forms of fenofibric acid because they are not interchangeable.
- Monitor for signs and symptoms of muscle-related adverse effects, especially when coadministered with a statin.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
The nurse should do the following for clients taking niacin:
- Assist the client in choosing appropriate over-the-counter versions when needed. Avoid flush-free niacin and choose extended-release products to maximize efficacy and minimize flushing.
- Administer an NSAID prior to administration if directed by the health care provider; if the client is already taking low-dose aspirin, the aspirin dose can be administered before niacin to limit additional NSAIDs.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking a bile acid sequestrant should:
- Take other drugs at least 1 hour before or 3–4 hours after bile acid sequestrant administration.
- Alert their health care provider, increase fluids and dietary fiber, and, if needed, take a stool softener if they experience constipation.
- Administer with meals as directed by their health care provider.
- Take vitamin supplementation if instructed to do so by their health care provider.
The client taking a fibrate should:
- Keep an accurate medication list so that health care professionals can assess for drug interactions.
- Monitor for adverse events and alert their health care provider with any concerns.
The client taking niacin should:
- Avoid choosing flush-free niacin for managing lipid levels.
- Ask their health care provider about possibly taking an NSAID before their niacin drug.
- Avoid hot drinks and alcoholic beverages around the time of administration to minimize flushing.