List of fibrates. Fibrates: Essential Medications for Managing Atherogenic Dyslipidemia

21.08.202316.06.2023 by alexxlab

What are fibrates and how do they work. How are fibrates administered and what are their indications. What are the potential side effects and contraindications of fibrate medications. How do fibrates compare to statins in managing cholesterol levels. What is the role of fibrates in treating hypertriglyceridemia. How do fibrates affect HDL cholesterol levels. What are the key considerations for healthcare providers when prescribing fibrates.

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Understanding Fibrates: A Powerful Class of Lipid-Lowering Medications

Fibrates, also known as fibric acid derivatives, are a class of medications used to manage dyslipidemia. These amphipathic carboxylic acids play a crucial role in combating the global epidemic of atherogenic dyslipidemia. While statins are effective in reducing low-density lipoprotein (LDL) cholesterol, fibrates excel in addressing elevated triglycerides and low high-density lipoprotein (HDL) cholesterol levels.

The unique properties of fibrates allow healthcare providers to tailor treatment strategies for individual patients, considering factors such as glucose metabolism, insulin resistance, and microvascular complications of diabetes mellitus.

Key Fibrate Medications

Fenofibrate
Gemfibrozil
Bezafibrate
Ciprofibrate

Mechanism of Action: How Fibrates Work to Improve Lipid Profiles

Fibrates exert their lipid-lowering effects through multiple mechanisms:

Reducing substrate availability for hepatic triglyceride synthesis
Promoting reverse cholesterol transport
Stimulating cellular fatty acid uptake
Modulating LDL receptor interactions
Enhancing LDL catabolism
Activating lipoprotein lipase (LPL)
Upregulating production of apolipoprotein AI and AII

How do fibrates activate lipoprotein lipase? Fibrates stimulate the transcription factors known as peroxisome proliferator-activated receptors (PPARs), particularly PPAR-alpha. This activation leads to increased LPL-mediated lipolysis, resulting in a reduction of small dense LDL particles, which are particularly prone to oxidation and contribute to atherosclerosis.

FDA-Approved Indications for Fibrate Therapy

The U.S. Food and Drug Administration (FDA) has approved fibrates for the following indications:

As an adjunct to dietary modifications in adults with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson types IIa and IIb)
As an adjunct to diet in adults with severe hypertriglyceridemia (Fredrickson types IV and V)

In addition to these approved uses, fibrates have shown promise in treating primary biliary cholangitis, although this remains an off-label application.

Administration and Dosing Guidelines for Fibrate Medications

Proper administration of fibrates is crucial for achieving optimal therapeutic outcomes. How should healthcare providers initiate fibrate therapy? It’s essential to start patients on an adequate lipid-lowering diet before introducing fibrate medication. Fibrates should be used as an adjunct to dietary modifications and other lipid-lowering treatments, rather than as first-line therapy.

Dosing Recommendations

Primary hypercholesterolemia or mixed dyslipidemia: Start with 120 mg daily
Severe hypertriglyceridemia: 40 mg to 120 mg daily, adjusted based on lipid levels
Renally impaired patients: Begin with 40 mg per day, with regular monitoring and dose adjustments
Geriatric patients: Dosing based on renal function

Fenofibrate, a commonly prescribed fibrate, is available in 40 mg and 120 mg tablets. Patient response should be assessed every 4 to 8 weeks, with dosage adjustments made accordingly.

Potential Adverse Effects and Monitoring Considerations

While fibrates are generally well-tolerated, healthcare providers should be aware of potential adverse effects:

Elevated liver enzymes (AST, ALT)
Increased serum creatinine phosphokinase (CPK) levels
Reversible increases in serum creatinine and homocysteine levels

What steps should healthcare providers take to monitor patients on fibrate therapy? Regular liver function tests, renal function assessments, and lipid profile measurements are essential. Additionally, monitoring for muscle-related symptoms is crucial, as fibrates may rarely cause myopathy or rhabdomyolysis, especially when combined with statins.

Fibrates vs. Statins: Complementary Approaches to Lipid Management

While both fibrates and statins are lipid-lowering medications, they have distinct roles in managing dyslipidemia. How do fibrates compare to statins in terms of their effects on lipid profiles?

Statins: Primarily reduce LDL cholesterol
Fibrates: More effective in lowering triglycerides and raising HDL cholesterol

In many cases, combination therapy with both statins and fibrates may be beneficial for patients with mixed dyslipidemia. However, healthcare providers must carefully monitor for potential drug interactions and increased risk of myopathy when using these medications together.

The Role of Fibrates in Managing Hypertriglyceridemia

Fibrates play a crucial role in the management of severe hypertriglyceridemia, a condition associated with increased risk of pancreatitis and cardiovascular disease. How effective are fibrates in reducing triglyceride levels?

Studies have shown that fibrates can reduce triglyceride levels by 30% to 50% in patients with severe hypertriglyceridemia. This significant reduction can help lower the risk of acute pancreatitis and may contribute to a decreased risk of cardiovascular events.

Fibrates in Combination with Omega-3 Fatty Acids

For patients with persistently elevated triglycerides despite fibrate therapy, combining fibrates with high-dose omega-3 fatty acids may provide additional benefits. This combination approach can lead to further reductions in triglyceride levels and improvements in overall lipid profiles.

Impact of Fibrates on HDL Cholesterol Levels

One of the unique benefits of fibrate therapy is its ability to raise HDL cholesterol levels. How do fibrates increase HDL cholesterol? Fibrates stimulate the production of apolipoprotein AI and AII in the liver, which are key components of HDL particles.

Typical increases in HDL cholesterol with fibrate therapy range from 10% to 20%. This elevation in HDL levels may contribute to improved cardiovascular outcomes, as HDL plays a crucial role in reverse cholesterol transport and has anti-inflammatory properties.

HDL Functionality

It’s important to note that while fibrates increase HDL cholesterol levels, the focus has shifted towards improving HDL functionality rather than simply raising HDL concentrations. Ongoing research is exploring how fibrates may enhance the cardioprotective properties of HDL particles.

Special Considerations for Healthcare Providers Prescribing Fibrates

When prescribing fibrates, healthcare providers should keep several important factors in mind:

Renal function: Dose adjustments are necessary for patients with impaired renal function
Hepatic function: Regular monitoring of liver enzymes is essential
Drug interactions: Be cautious when combining fibrates with statins or anticoagulants
Pregnancy and lactation: Fibrates are generally contraindicated during pregnancy and breastfeeding
Elderly patients: Consider age-related changes in renal function when dosing

How can healthcare providers optimize fibrate therapy for their patients? Individualized treatment plans, regular monitoring, and patient education are key components of successful fibrate therapy. Encouraging adherence to lifestyle modifications, including diet and exercise, can enhance the effectiveness of fibrate treatment.

Emerging Research and Future Directions

As our understanding of lipid metabolism and cardiovascular disease continues to evolve, ongoing research is exploring new applications and formulations of fibrates. Some areas of interest include:

Novel fibrate compounds with improved efficacy and safety profiles
Combination therapies with other lipid-lowering agents
Potential roles in managing non-alcoholic fatty liver disease (NAFLD)
Effects on cardiovascular outcomes in specific patient populations

Healthcare providers should stay informed about the latest developments in fibrate research to provide optimal care for their patients with dyslipidemia.

Interprofessional Strategies for Optimizing Fibrate Therapy

Effective management of dyslipidemia with fibrates requires a collaborative approach involving multiple healthcare professionals. How can interprofessional teams improve care coordination and communication to enhance outcomes with fibrate therapy?

Regular team meetings to discuss patient progress and treatment plans
Clear communication channels between physicians, pharmacists, and nurses
Shared decision-making processes that involve patients in their care
Coordinated patient education efforts across all team members
Standardized protocols for monitoring and managing adverse effects

By implementing these strategies, healthcare teams can ensure that patients receive comprehensive care and support throughout their fibrate treatment journey.

Role of Clinical Pharmacists

Clinical pharmacists play a crucial role in optimizing fibrate therapy. Their responsibilities may include:

Reviewing medication regimens for potential drug interactions
Providing patient education on proper medication use and potential side effects
Monitoring laboratory values and recommending dose adjustments
Collaborating with physicians to develop individualized treatment plans

Integrating clinical pharmacists into the care team can lead to improved medication management and better patient outcomes.

Patient Education and Adherence to Fibrate Therapy

Successful fibrate therapy relies heavily on patient understanding and adherence to treatment. How can healthcare providers improve patient education and promote adherence to fibrate medications?

Provide clear, easy-to-understand information about the medication’s purpose and benefits
Discuss potential side effects and what to do if they occur
Emphasize the importance of regular follow-up appointments and laboratory tests
Offer strategies for incorporating medication into daily routines
Address any concerns or misconceptions about fibrate therapy

Encouraging patients to actively participate in their care and providing ongoing support can significantly improve adherence to fibrate therapy and overall treatment outcomes.

Lifestyle Modifications

While fibrates are effective in managing dyslipidemia, they should be used in conjunction with lifestyle modifications. Healthcare providers should educate patients on the importance of:

Following a heart-healthy diet low in saturated fats and cholesterol
Engaging in regular physical activity
Maintaining a healthy weight
Quitting smoking
Limiting alcohol consumption

By combining fibrate therapy with these lifestyle changes, patients can maximize the benefits of treatment and improve their overall cardiovascular health.

Monitoring and Long-term Management of Patients on Fibrate Therapy

Long-term management of patients on fibrate therapy requires ongoing monitoring and adjustments to ensure optimal outcomes. What key aspects should healthcare providers focus on during follow-up visits?

Regular lipid profile assessments to evaluate treatment efficacy
Monitoring of liver function tests and creatinine levels
Assessment of muscle-related symptoms and CPK levels
Evaluation of cardiovascular risk factors and overall health status
Review of medication adherence and any barriers to treatment

By implementing a comprehensive monitoring plan, healthcare providers can identify and address any issues early, ensuring the continued effectiveness and safety of fibrate therapy.

Adjusting Treatment Plans

As patients’ health status and lipid profiles change over time, treatment plans may need to be adjusted. Considerations for modifying fibrate therapy include:

Dose adjustments based on lipid level responses
Addition or removal of complementary lipid-lowering medications
Modifications to account for changes in renal or hepatic function
Addressing any emerging side effects or tolerability issues

Flexibility in treatment approaches and ongoing communication with patients are essential for maintaining the long-term success of fibrate therapy.

Future Perspectives: Emerging Research and Potential Applications of Fibrates

As our understanding of lipid metabolism and cardiovascular disease continues to evolve, researchers are exploring new applications and formulations of fibrates. What are some promising areas of investigation in fibrate research?

Development of novel fibrate compounds with enhanced efficacy and safety profiles
Exploration of fibrates’ potential roles in managing non-alcoholic fatty liver disease (NAFLD)
Investigation of fibrates’ effects on cardiovascular outcomes in specific patient populations
Evaluation of combination therapies with other lipid-lowering agents or novel cardiovascular medications
Assessment of fibrates’ impact on inflammation and other cardiovascular risk factors

As research progresses, healthcare providers should stay informed about the latest developments to provide the most up-to-date and effective care for their patients with dyslipidemia.

Personalized Medicine Approaches

The future of fibrate therapy may involve more personalized approaches to treatment. Ongoing research is exploring:

Genetic markers that may predict response to fibrate therapy
Biomarkers for identifying patients most likely to benefit from fibrates
Tailored combination therapies based on individual patient profiles
Novel drug delivery systems for improved efficacy and reduced side effects

These advancements in personalized medicine may lead to more targeted and effective use of fibrates in managing dyslipidemia and reducing cardiovascular risk.

Fibrate Medications – StatPearls – NCBI Bookshelf

Gauri Singh; Ricardo Correa.

Author Information and Affiliations

Last Update: May 1, 2023.

Continuing Education Activity

Fibrates are a class of drugs utilized in the management and treatment of dyslipidemia. This activity reviews the indications, action, and contraindications for fibrates as a valuable agent in managing serum cholesterol levels. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., monitoring, relevant interactions, etc.) pertinent for members of the healthcare team involved in the care of patients with atherogenic dyslipidemia and related conditions.

Objectives:

Identify the mechanism of action and administration of fibrates.
Describe the adverse effects and contraindications of fibrates.
Review the potential toxicity of fibrates.
Outline interprofessional team strategies for improving care coordination and communication to advance fibrates and improve outcomes.

Access free multiple choice questions on this topic.

Indications

The fibrates are a type of amphipathic carboxylic acids belonging to the class of drugs used to lower serum cholesterol levels. They are currently the most important class of drugs combating the worldwide epidemic of atherogenic dyslipidemia. Statins help reduce the levels of low-density lipoprotein cholesterol (LDL) but do not exert much of an effect on serum triglyceride or HDL levels, where the use of fibrates is required. Research shows that the effects of different fibrate medications, while essentially being the same, differ slightly regarding their impact on glucose metabolism, insulin resistance, intermittent claudication, and microvascular effects of diabetes mellitus; this provides the option of tailoring therapy as per the needs of every patient.[1] The FDA approved indications of fibrates include :

For use as an adjunct to dietary modifications (restricted in saturated fats and cholesterol) in adults with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson type IIa and IIb). Fibrates help to reduce serum LDL, total cholesterol, triglycerides, apolipoprotein B (Apo-B) and increase high-density lipoprotein cholesterol (HDL).
To be used, an adjunct to dietary modifications in adults with severe hypertriglyceridemia (Fredrickson type IV and V).

A non-FDA-approved use of fibrates is primary biliary cholangitis.

Mechanism of Action

Fibrates work by a combination of the following mechanisms to cause their hypotriglyceridemic effects[2]:

Reduce the availability of substrates to allow triglyceride synthesis in the liver.
Reverse cholesterol movement and stimulate cellular fatty acid uptake and modulate low-density lipoprotein (LDL) receptor and ligand interaction. Fibrates promote receptor-mediated clearance of LDL after stimulating its secretion, causing this catabolism to occur at a 20% greater rate compared to an untreated patient. This action results in an overall decrease in very-low-density lipoproteins (VLDL).
Small dense LDL, a fraction of LDL that produces the maximum peroxidation products, is reduced via the action of fibrates by activating lipoprotein lipase (LPL). Fibrates increase this LPL mediated lipolysis via activation of transcription factors for peroxisome proliferator-activated receptors (PPAR).[3]

Fibrates also work to increase high-density lipoprotein (HDL) levels by upregulating the production of Apo-AI and apo-AII in the liver.

Administration

Before starting fibrate therapy, patients should start on an adequate lipid-lowering diet. It should be used only as an adjunct to lipid-lowering diet and medication and not as a first-line mode of therapy.

Fibrates are administered orally, ideally as once a day tablets. According to the FDA, the dosing of fibrates in adults is as follows, adjusted for the patient profile :

Primary hypercholesterolemia or mixed dyslipidemia – Start with 120 mg daily.
Severe hypertriglyceridemia – The dose ranges from 40 mg to 120 mg daily and is adjusted according to lipid levels.
Renally impaired patients – Initiate with 40 mg per day. Conduct regular renal function tests and serum cholesterol levels and up-titrate the drug as required.
Geriatric patients – The dosing is per the renal function of the patient.

The above regime is for fenofibrate, which is available as 40 mg and 120 mg tablets. The patient’s response to it must be measured every 4 to 8 weeks, followed by adjusting the drug dosage.

Adverse Effects

The following is a list of adverse effects of fibrates:

The most common adverse effects of this drug class include reporting of deranged AST, ALT levels, along with infrequent elevations in serum CPK (creatinine phosphokinase) levels during therapy.
Most likely, due to the effect mediated by PPAR-alpha, fibrates can reversibly increase serum creatinine and homocysteine levels. But clinical trials have failed to prove renal failure associated with this.
Patients can present with leg cramps, abdominal pain, etc. , as fibrates can cause a slightly increased risk (less than 1.0%) of myopathy, cholelithiasis, and venous thrombosis.
Fibrates generally should be avoided in combination with statins since they can inhibit statin metabolism, causing an increased risk of myopathy. Recommendations are to always to measure serum creatinine levels and renal function before using the two drugs simultaneously. Gemfibrozil has proved to be unsafe for this interaction, whereas clinicians can still use bezafibrate and fenofibrate.
Discontinue fibrate therapy or reduce the fibrate dose if a clinically significant elevation of serum creatinine occurs in the patient, after excluding all possible causes for the same.[4]

Contraindications

The contra-indications to the use of fibrate therapy are:

Known hypersensitivity to the drug class.
Active liver disease, as fibrates are shown to be hepatotoxic if pre-existing liver inflammatory states exist. [5]
Active gall bladder disease as fibrates cause a PPAR-Alpha mediated downregulation in bile acid production, which, in turn, is responsible for an increased tendency to form gall stones.[6]
Severe renal dysfunction, including patients receiving dialysis therapy.

Monitoring

Fibrates are usually safe drugs that do not need routine monitoring except in the following cases:

Co-administration with statins increases the risk for myopathy. Monitor these patients for serum CPK levels, especially if they have diabetes, hypothyroidism, or renal failure.
Monitor renal function tests in patients with pre-existing deranged renal function.
Monitor serum transaminases since fibrates can sometimes elevate these levels.
Conduct gallbladder studies in patients with pre-existing gallbladder disease or if cholelithiasis is suspected.
Monitor PT/INR levels at least thrice a week when co-administering with coumarin anti-coagulants to prevent bleeding complications as fibrates are known to potentiate the effects of the former. [7]

Toxicity

There is no known antidote to fibrate toxicity. If possible, eliminate any unabsorbed drug via emesis or gastric lavage, maintaining the necessary common precautions for airway protection.
If a patient happens to overdose on fibrates, do not consider hemodialysis as fibrates are highly plasma protein-bound drugs.

Enhancing Healthcare Team Outcomes

Managing appropriate drug use requires free-flowing and efficient communication between the entire interprofessional healthcare team, including clinicians, mid-level practitioners, nurses, and pharmacists. The same applies to the use of fibrates. Health professionals should bear in mind the adverse outcome of fibrates regarding liver function tests (LFTs) and ensure that there is regular testing, especially if the patient has pre-existing liver disease. Fibrates are also notorious for causing drug interactions, and health professionals should be thorough with the patient’s medication history before prescribing them. If a patient is already on statins, monitor carefully for the development of myopathies, evaluate clotting studies for those on anticoagulants, etc. Most importantly, it is the responsibility of healthcare providers to counsel the patients about the adverse effects of this drug and ensure they report any new or untoward symptoms(such as muscle cramps, abdominal pain, indigestion, etc.) after initiating the drug.

An interprofessional team effort is necessary to accomplish the above. The clinician will make the decision to initiate fibrate therapy based on the case facts before them. Still, they would do well to include a pharmacist who can review the patient’s current medications to check for possible drug interactions and verify appropriate dosing. The pharmacist can also assist in choosing a specific fibrate depending on the patient’s particular parameters. Nursing should be aware of the signs of the most common interactions and adverse effects; they can check on patient compliance and monitor for adverse events, alerting the prescriber when appropriate. In this way, fibrate therapy can achieve the best possible result with minimal chance of encountering adverse effects. [Level 5]

Review Questions

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References

1.: Tenenbaum A, Fisman EZ. Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction. Cardiovasc Diabetol. 2012 Oct 11;11:125. [PMC free article: PMC3489608] [PubMed: 23057687]
2.: Shepherd J. Mechanism of action of fibrates. Postgrad Med J. 1993;69 Suppl 1:S34-41. [PubMed: 8497455]
3.: Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998 Nov 10;98(19):2088-93. [PubMed: 9808609]
4.: Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol. 2007 Mar 19;99(6A):3C-18C. [PubMed: 17368275]
5.: Škop V, Trnovská J, Oliyarnyk O, Marková I, Malínská H, Kazdová L, Zídek V, Landa V, Mlejnek P, Šimáková M, Kůdela M, Pravenec M, Šilhavý J. Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein. Physiol Res. 2016 Dec 13;65(6):891-899. [PubMed: 27539098]
6.: Post SM, Duez H, Gervois PP, Staels B, Kuipers F, Princen HM. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression. Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1840-5. [PubMed: 11701475]
7.: Ascah KJ, Rock GA, Wells PS. Interaction between fenofibrate and warfarin. Ann Pharmacother. 1998 Jul-Aug;32(7-8):765-8. [PubMed: 9681093]

: Disclosure: Gauri Singh declares no relevant financial relationships with ineligible companies.
: Disclosure: Ricardo Correa declares no relevant financial relationships with ineligible companies.