How does fenofibrate affect fatty liver in alcohol-treated rats. What are the effects of fenofibrate on hyperlipidemia in patients with alcoholic fatty liver. Can fenofibrate prevent or reduce alcoholic fatty liver disease.

Understanding Alcoholic Fatty Liver Disease and the Potential of Fenofibrate

Alcoholic fatty liver disease is a common condition among chronic alcoholics, characterized by the accumulation of fat in liver cells. Despite its prevalence, there has been a lack of practical approaches to prevent or treat this condition. However, recent research has shed light on a potential solution: fenofibrate, a medication belonging to the fibrate class of drugs.

Fenofibrate works by binding to peroxisome proliferator-activated receptor-alpha (PPAR-α), which in turn induces beta-oxidation enzymes of fatty acids in mitochondria. This mechanism suggests that fenofibrate could potentially help in reducing fat accumulation in the liver and address associated lipid abnormalities.

The Rat Study: Investigating Fenofibrate’s Effect on Alcohol-Induced Fatty Liver

To explore the potential benefits of fenofibrate in treating alcoholic fatty liver, researchers conducted a study using male Wistar rats. The experimental design was as follows:

• Duration: 4 weeks
• Diet: Liquid diet containing either ethanol (36% of total calories) or an isocaloric carbohydrate substitute
• Fenofibrate administration: Oral, at concentrations of 0, 5, or 30 mg/kg body weight/day

Key Findings from the Rat Study

The results of the rat study were promising and demonstrated several positive effects of fenofibrate:

1. Reduced fatty degeneration: Three out of five rats treated with 5 mg of fenofibrate and all rats treated with 30 mg showed no signs of fatty liver degeneration.
2. Decreased hepatic triglyceride content: Rats treated with 30 mg of fenofibrate exhibited significantly lower levels of triglycerides in their livers compared to untreated rats.
3. Improved serum lipid profile: Both serum triglyceride and total cholesterol levels decreased after fenofibrate treatment.

These findings suggest that fenofibrate may have a dose-dependent protective effect against alcohol-induced fatty liver in rats.

Human Pilot Study: Fenofibrate’s Effect on Alcoholic Fatty Liver Patients

To assess the potential benefits of fenofibrate in humans, a small pilot study was conducted involving eight patients diagnosed with alcoholic fatty liver. The study parameters were:

• Duration: 4 weeks
• Fenofibrate dosage: 200 mg/day

Results of the Human Pilot Study

The preliminary results from the human study were encouraging:

Serum triglyceride levels decreased significantly in the eight alcoholic patients treated with fenofibrate. This finding aligns with the results observed in the rat study and suggests that fenofibrate may have similar beneficial effects on lipid metabolism in humans with alcoholic fatty liver.

Mechanisms of Fenofibrate’s Action in Alcoholic Fatty Liver

To understand how fenofibrate exerts its effects on alcoholic fatty liver, it’s important to delve into its mechanisms of action:

1. PPAR-α activation: Fenofibrate binds to and activates PPAR-α, a nuclear receptor that plays a crucial role in regulating lipid metabolism.
2. Enhanced fatty acid oxidation: Activation of PPAR-α leads to increased expression of genes involved in fatty acid oxidation, particularly in mitochondria.
3. Reduced lipogenesis: Fenofibrate may also suppress the expression of genes involved in lipid synthesis, further contributing to the reduction of fat accumulation in the liver.
4. Improved insulin sensitivity: Some studies suggest that fenofibrate may enhance insulin sensitivity, which could indirectly benefit liver health in the context of alcoholic fatty liver disease.

These mechanisms collectively contribute to the reduction of fat accumulation in the liver and improvement of lipid profiles observed in both the rat and human studies.

Potential Clinical Implications of Fenofibrate Use in Alcoholic Fatty Liver

The findings from both the rat study and the human pilot study suggest several potential clinical implications for the use of fenofibrate in managing alcoholic fatty liver:

• Prevention of fatty liver progression: Fenofibrate may help prevent the development or progression of fatty liver in individuals with chronic alcohol consumption.
• Lipid profile improvement: The medication’s ability to reduce serum triglycerides and cholesterol levels could benefit overall cardiovascular health in patients with alcoholic fatty liver.
• Potential liver protection: By reducing fat accumulation in the liver, fenofibrate might help mitigate liver damage associated with chronic alcohol use.
• Adjunct therapy: Fenofibrate could potentially be used as an adjunct therapy alongside other interventions for managing alcoholic liver disease.

Do these findings mean fenofibrate is ready for widespread use in treating alcoholic fatty liver? While the results are promising, larger clinical trials are needed to confirm the efficacy and safety of fenofibrate in this context before it can be recommended as a standard treatment.

Limitations and Future Research Directions

Despite the encouraging results, it’s important to acknowledge the limitations of the current studies and identify areas for future research:

1. Sample size: The human pilot study involved only eight patients, which limits the generalizability of the results.
2. Study duration: Both the rat and human studies were conducted over a relatively short period (4 weeks). Longer-term studies are needed to assess the sustained effects and safety of fenofibrate treatment.
3. Dose optimization: Further research is required to determine the optimal dosage of fenofibrate for treating alcoholic fatty liver in humans.
4. Combination therapies: Investigating the potential synergistic effects of fenofibrate with other treatments for alcoholic liver disease could yield valuable insights.
5. Mechanisms of action: While the basic mechanisms of fenofibrate’s action are understood, more detailed studies on its effects on specific liver pathways in the context of alcohol-induced damage are warranted.

How can future research address these limitations? Larger, randomized controlled trials with longer follow-up periods will be crucial in validating the efficacy and safety of fenofibrate for alcoholic fatty liver. Additionally, studies comparing fenofibrate to other treatments or investigating combination therapies could help establish its place in the treatment landscape.

Potential Side Effects and Considerations for Fenofibrate Use

While the studies discussed focused primarily on the beneficial effects of fenofibrate, it’s important to consider potential side effects and contraindications:

• Gastrointestinal disturbances: Some patients may experience nausea, stomach pain, or diarrhea.
• Muscle pain: In rare cases, fenofibrate can cause muscle pain or weakness, which may be a sign of a serious condition called rhabdomyolysis.
• Liver function changes: Fenofibrate can affect liver enzyme levels, necessitating regular monitoring of liver function during treatment.
• Interactions with other medications: Fenofibrate may interact with certain drugs, including blood thinners and statins, requiring careful management in patients taking multiple medications.
• Kidney function: Patients with impaired kidney function may need dose adjustments or may not be suitable candidates for fenofibrate treatment.

Can fenofibrate be safely used in all patients with alcoholic fatty liver? The answer is not straightforward. While the preliminary results are promising, individual patient factors, including overall health status, concurrent medications, and the severity of liver disease, must be carefully considered before initiating fenofibrate treatment.

The Broader Context: Alcoholic Fatty Liver Disease Management

While the potential of fenofibrate in treating alcoholic fatty liver is exciting, it’s crucial to place this treatment option within the broader context of alcoholic fatty liver disease management:

1. Alcohol cessation: The primary and most effective intervention for alcoholic fatty liver disease remains abstinence from alcohol.
2. Dietary modifications: A balanced, nutritious diet can support liver health and aid in recovery from fatty liver disease.
3. Weight management: For overweight or obese individuals, weight loss can significantly improve liver health and reduce fat accumulation.
4. Exercise: Regular physical activity has been shown to benefit liver health and may complement other interventions.
5. Vitamin supplementation: Some patients may benefit from specific vitamin supplements, particularly B-complex vitamins, which are often deficient in chronic alcoholics.

How does fenofibrate fit into this comprehensive approach to managing alcoholic fatty liver? If further research confirms its efficacy and safety, fenofibrate could potentially serve as a valuable adjunct therapy, particularly for patients with persistent fatty liver or lipid abnormalities despite lifestyle modifications.

In conclusion, the studies on fenofibrate’s effects on alcoholic fatty liver in both rats and humans offer promising initial results. The medication’s ability to reduce hepatic fat accumulation and improve lipid profiles suggests it could be a valuable tool in managing this common condition. However, larger clinical trials and long-term studies are necessary to fully establish its efficacy, safety, and optimal use in the treatment of alcoholic fatty liver disease. As research progresses, fenofibrate may emerge as an important component of a multifaceted approach to managing this challenging liver condition.

Effect of fenofibrate on fatty liver in rats treated with alcohol

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. 2001 Jun;25(6 Suppl):75S-9S.

doi: 10.1097/00000374-200106001-00017.

M Tsutsumi And 
¹
, S Takase

Affiliations

Affiliation

• ¹ Division of Gastroenterology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

• PMID:

  11410747

• DOI:

  10.1097/00000374-200106001-00017

M Tsutsumi And et al.

Alcohol Clin Exp Res.

2001 Jun.

. 2001 Jun;25(6 Suppl):75S-9S.

doi: 10.1097/00000374-200106001-00017.

Authors

M Tsutsumi And 
¹
, S Takase

Affiliation

• ¹ Division of Gastroenterology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

• PMID:

  11410747

• DOI:

  10.1097/00000374-200106001-00017

Abstract

Background:

Although fatty liver and hyperlipemia are common in chronic alcoholics, there is no practical approach to prevent alcoholic fatty liver. Recently, it has been reported that fibrates bind to peroxisome proliferator-activated receptor-alpha and induce beta-oxidation enzymes of fatty acid in mitochondria. In this study, we investigated the effect of fenofibrate, one of the fibrates, on fatty liver in rats induced by chronic alcohol feeding. Furthermore, we studied the effect of fenofibrate on hyperlipemia in patients with alcoholic fatty liver.

Methods:

Male Wistar rats were treated with liquid diet that contained ethanol (36% of total calories) or an isocaloric carbohydrate instead of ethanol for 4 weeks. Fenofibrate was administered orally with the liquid diets for 4 weeks at a concentration of either 0, 5, or 30 mg/kg body weight/day. As a pilot study, eight patients with alcoholic fatty liver were treated with 200 mg/day of fenofibrate for 4 weeks.

Results:

After fenofibrate administration, fatty degeneration of liver was not observed in three of the five rats treated with 5 mg and in all rats treated with 30 mg of fenofibrate. Hepatic triglyceride content was decreased significantly in rats treated with 30 mg of fenofibrate compared with the rats not treated with fenofibrate. Serum triglyceride and total cholesterol levels also were decreased after treatment with fenofibrate. In eight alcoholic patients treated with 200 mg of fenofibrate for 4 weeks, serum triglyceride level decreased significantly compared with the levels before treatment. All patients continued alcohol consumption during fenofibrate administration.

Conclusion:

The results of the present investigation suggest that fenofibrate may be useful to prevent alcoholic fatty liver. Further studies with larger numbers of patients are necessary to obtain definitive results.

Cited by

• The hepatic BMAL1/AKT/lipogenesis axis protects against alcoholic liver disease in mice via promoting PPARα pathway.

  Zhang D, Tong X, Nelson BB, Jin E, Sit J, Charney N, Yang M, Omary MB, Yin L.

  Zhang D, et al.
  Hepatology. 2018 Sep;68(3):883-896. doi: 10.1002/hep.29878. Epub 2018 May 20.
  Hepatology. 2018.

  PMID: 29534306
  Free PMC article.

• Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels.

  Rivera-Meza M, Muñoz D, Jerez E, Quintanilla ME, Salinas-Luypaert C, Fernandez K, Karahanian E.

  Rivera-Meza M, et al.
  Front Behav Neurosci. 2017 Jul 14;11:133. doi: 10.3389/fnbeh.2017.00133. eCollection 2017.
  Front Behav Neurosci. 2017.

  PMID: 28769774
  Free PMC article.

• Alcohol Modulation of the Postburn Hepatic Response.

  Chen MM, Carter SR, Curtis BJ, O’Halloran EB, Gamelli RL, Kovacs EJ.

  Chen MM, et al.
  J Burn Care Res. 2017 Jan/Feb;38(1):e144-e157. doi: 10.1097/BCR.0000000000000279.
  J Burn Care Res. 2017.

  PMID: 26284631
  Free PMC article.

  Review.

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There are 2 alcohol/food/lifestyle interactions with fenofibrate.

Fenofibrate may increase the blood levels and effects of nicotine. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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fibric acid derivatives – HDL cholesterol

There have been reports of severe decreases in HDL cholesterol (HDL-C) levels (as low as 2 mg/dL) occurring in diabetic and non-diabetic patients initiated on fibric acid derivatives therapy. The decrease has been reported to occur within 2 weeks to years after initiation of therapy. It is recommended that HDL-C levels be checked within the first few months after initiation therapy and if a severely depressed HDL-C level is detected, therapy with these agents should be withdrawn. Monitor HDL-C level until it has returned to baseline, and therapy with these agents should not be re-initiated in these patients.

References

1. “Product Information. Lopid (gemfibrozil).” Parke-Davis
   (2002):
2. Thompson CH, Irish A, Kemp GJ, Taylor DJ, Radda GK “Skeletal muscle metabolism before and after gemfibrozil treatment in dialysed patients with chronic renal failure. ” Clin Nephrol 45
   (1996): 386-9
3. Gorriz JL, Sancho A, Lopezmartin JM, Alcoy E, Catalan C, Pallardo LM “Rhabdomyolysis and acute renal failure associated with gemfibrozil therapy.” Nephron 74
   (1996): 437-8
4. “Product Information. Tricor (fenofibrate).” Abbott Pharmaceutical
   (2001):

View all 4 references

Fenofibrate drug interactions

There are 137 drug interactions with fenofibrate.

Fenofibrate disease interactions

There are 7 disease interactions with fenofibrate which include:

• biliary cirrhosis
• cholelithiasis
• HDL cholesterol
• liver disease
• renal dysfunction
• rhabdomyolysis
• hematological changes

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.

Major	Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
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Therapy » Effect of fenofibrate on dyslipidemia and diabetic polyneuropathy in patients with type 2 diabetes mellitus

• Journal archive
  /
• 2016
  /
• #4

Effect of fenofibrate on dyslipidemia and diabetic polyneuropathy in patients with type 2 diabetes mellitus

T.Yu. Demidova, N.I. Drozdova

Russian Medical Academy of Postgraduate Education, Department of Endocrinology, Moscow

The incidence of diabetes mellitus (DM) is increasing every year throughout the world. Type 2 diabetes is getting younger and is becoming an increasing problem due to early disability due to the development of microvascular complications. The most common complication of DM is diabetic polyneuropathy, which can lead to diabetic foot development and amputation. In addition, the course of DM is accompanied by the presence of hypertriglyceridemia, which in turn is a risk factor for the development of cardiovascular complications (heart attack, stroke) in patients with DM. Currently, an urgent task in the treatment of DM is the development of treatment methods aimed at preventing the development of late microvascular complications. According to the results of many studies, the use of fenofibrate in patients with type 2 diabetes normalizes lipid metabolism, significantly reduces the progression of diabetic neuropathy and reduces the number of amputations associated with diabetes.

Keywords: amputation, diabetic neuropathy, hypertriglyceridemia, fenofibrate, diabetes mellitus

The prevalence of diabetes mellitus (DM) is steadily increasing worldwide, significantly exceeding the forecasts of the World Health Organization (WHO). Thus, according to WHO experts, by 2025 there will be about 300 million people diagnosed with diabetes in the world. However, already in 2015, according to the International Diabetes Federation, the number of cases of diabetes in the world amounted to 415 million. It is expected that by 2035 this figure will increase to 592 million people [1]. The vast majority of patients suffer from type 2 diabetes. Data on the prevalence of type 2 diabetes obtained in the NATION study (the first national epidemiological cross-sectional study conducted on the territory of the Russian Federation from September 2013 to February 2015) suggest that among the adult population of Russia aged 20– At the age of 79, about 5.9 million people have type 2 diabetes. The results of the NATION study also indicate that a significant number of cases of type 2 diabetes (~54%) in Russia are not diagnosed [2]. Thus, the Russian Federation ranks fifth among the ten countries with the largest population suffering from diabetes. Today, there is a tendency not only to increase the incidence of type 2 diabetes, but also the development of this pathology at a younger age, which is associated with the urbanization of the territory, an increase in the prevalence of obesity and a sedentary lifestyle. An increasing problem is the early disability of patients with type 2 diabetes due to the development of late microvascular complications. One of the current trends in modern medicine is the development of methods for the prevention and treatment of complications of type 2 diabetes.

According to the WHO, there are several types of dyslipidemia (DLP) (Table 1). Types IIa, IIb, and III are atherogenic, while types I, IV, and V are more common in individuals with type 2 diabetes and metabolic syndrome (MS) and are therefore considered relatively atherogenic. Isolated hypertriglyceridemia (HTG) accounts for approximately 45% of the entire DLP population.

For type 2 diabetes and MS, HTG (type IV) is more characteristic, which is also combined with a low level of high-density lipoprotein (HDL) and a predominance of low-density lipoprotein (LDL) particles. In combination with such risk factors as insulin resistance, hyperglycemia, arterial hypertension, and abdominal obesity, DLP contributes to pathological changes in the microcirculatory bed, causing complications typical of DM, such as diabetic retinopathy, neuropathy, and damage to the arteries of the lower extremities [3]. Risks associated with HTH include heart attacks, strokes, and overall mortality in patients with type 2 diabetes. HTG is a proven predictor of overall mortality in patients with type 2 diabetes: high triglyceride levels increase the risk of death by 65% ​​compared with normal levels [4]. HTH is associated with cardiovascular mortality: at a plasma triglyceride level >133 mg/dl (>1.5 mmol/l), the relative risk of cardiovascular mortality increases by about 3 times (p<0.001) [5]. At high levels of triglycerides, the risk of stroke increases by 2 times [6]. The target triglyceride level for patients with type 2 diabetes is 1.7 mmol/l, which is lower than recommended for the general population of the same age and gender.

Recommendations for the treatment of DLP currently highlight fibric acid derivatives (fibrates) as first choice drugs for patients with HTG. Fibrates have been used in clinical practice for over 60 years. They predominantly lower triglyceride levels, moderately increase HDL levels, and have a number of pleiotropic effects. Fibrates affect the activation of nuclear receptors PPAR α (alpha receptors, the activation of which leads to the proliferation of peroxisomes – organelles that produce enzymes that enhance the activity of lipoprotein lipase). Two drugs from the fibrate class are registered in the Russian Federation: fenofibrate (Trycor) and ciprofibrate (Table 2) [3].

Fibrates lower triglycerides, increase HDL and moderately lower LDL. Fibrates are prescribed mainly for DLP types IIb, IV, V in combination with low HDL in patients with MS, type 2 diabetes, familial combined hyperlipidemia and familial endogenous HTG. Fibrates affect the composition of LDL particles, converting them from small and dense to larger and less atherogenic LDL particles. In addition, fibrates reduce the activity of the cholesterol ester transfer protein (CS), which is accompanied by an increase in HDL levels. Fibrates stimulate the reverse transport of cholesterol and increase the synthesis of bile acids in the liver. Fibrates of the third generation (pheno- and ciprofibrate) do not increase the lithogenicity of bile. Fenofibrate (Trycor) reduces triglycerides by 55%, increases HDL by 30%, and to a lesser extent affects LDL and total cholesterol.

In a large open-label 6-month study conducted in Belgium on a large cohort (1148 patients with DDP), it was shown that treatment with fenofibrate leads to an average decrease in LDL levels by 24.4%, triglycerides by 36.6% and an increase in the average level of HDL by 15.2% [29]. Similar results were obtained in Germany in a 12-week monitoring program of fenofibrate use by general practitioners in 9884 patients [30]. This study, conducted on such a large number of patients with various DLP, led to the conclusion that the greater the deviation from the norm of each indicator, the more pronounced the effect of the normalizing effect of fenofibrate. The decrease in LDL was 22-23%, the level of triglycerides decreased by an average of 30% while increasing HDL by 24-25%. Fenofibrate was well tolerated, adverse side effects were detected in 3.8% of patients, and only in 0.4% they were serious. Since the decrease in HDL has an independent atherogenic significance, a special study was conducted in which 709In 8 patients with DLP, fenofibrate has been shown to increase HDL levels, depending on the initial HDL value [31]. The degree of increase in HDL was the highest – by 90.2% with a very low initial level of HDL <0.65 mmol/l (n=254). In the cohort of individuals with HDL level <0.90 mmol/l (n=2078), the degree of HDL increase was 44.39%, with HDL level <1.03 mmol/l (n=3535) its increase was 36.1%.

Statins belong to another class of lipid-lowering drugs, they have a pronounced effect on LDL, but the level of triglycerides is reduced by an average of 15–20%, and the level of HDL is increased by 6–10% [3]. Fenofibrate (Trycor) can be combined with simva-, atorva-, fluva-, and rosuvastatin [3], which are the standard for multifactorial management of type 2 diabetes, but retain a fairly large residual risk of vascular accidents. Therefore, in a situation of isolated HTG, the use of fenofibrate is more justified. At the same time, patients with mixed DLP should receive statins, which can ideally be combined with fenofibrate in case of unmet triglyceride and HDL targets.

In randomized prospective placebo-controlled programs for primary and secondary prevention of cardiovascular diseases using fibrates of new generations, in particular the drug Traykor, it was shown that with positive effects on the level of lipid and apolipoprotein indicators of the lipoprotein spectrum in the blood plasma, on clinical episodes of coronary artery disease and angiographic manifestations of coronary atherosclerosis, the use of fenofibrate does not cause adverse events previously shown for the first generation fibrate – clofibrate [32-36].

The ACCORD (The Action to Control Cardiovascular Risk in Diabetes) study, which lasted over 5 years, showed that the addition of fenofibrate to statins additionally reduced the risk of cardiovascular events in patients with type 2 diabetes by 31%, but did not increase the risks side events. In the largest fibrate study, FIELD (Fenofibrate Intervention and Event Lowering in Diabetes), which examined the effectiveness of both primary and secondary prevention of cardiovascular events in a population of 9In 795 patients with type 2 diabetes who did not have indications for lipid-lowering therapy, the following results were obtained: the risk of achieving the primary endpoint, which included death from coronary artery disease or non-fatal heart attack, decreased by 19%. In a subsequent subanalysis in the group of patients with elevated triglycerides and reduced HDL, fenofibrate (Trycor) significantly reduced the incidence of cardiovascular events by 27%.

The prevalence of diabetic polyneuropathy (DPN) is up to 80% of all patients with diabetes. There are many different theories explaining the causes and mechanisms of development of DPN. At the same time, hyperglycemia is the main established pathogenetic factor in the occurrence of DPN [7, 8]. Hyperglycemia causes neuronal damage due to an intracellular increase in glucose levels with excessive metabolism (with activation of the polyol glucose utilization pathway under the action of aldoreductase) and the accumulation of toxic products (sorbitol, fructose), an increase in intracellular osmotic pressure, and neuronal edema. It is noted that hyperglycemia with the accumulation of toxic metabolites and end products of glycation enhances the formation of free radicals with the development of “oxidative stress” and a decrease in the level of myo-inositol, which also has a damaging effect on neurons. In recent years, data have emerged indicating the involvement of systemic chronic low-grade inflammation in the development of DPN. It has been proven that inflammatory cytokines can cause damage to the myelin sheath and sensitize peripheral receptors that cause neuropathic pain [9]. It is known that an increase in the expression of tumor necrosis factor α (TNF-α) leads to toxic damage and demyelination of oligodendrocytes. In addition, TNF-α stimulates the secretion of interleukins (IL)-1β and IL-6, as well as other inflammatory factors, which indirectly enhances its detrimental effect on the peripheral parts of the nervous system [10]. In addition, TNF-α inhibits the activity of nitric oxide synthase in endothelial cells, leading to a decrease in NO-induced vasodilation. This, in turn, promotes the expression of growth factors and cell adhesion molecules, resulting in the development of endothelial dysfunction and a number of pathological changes in the endoneural microvascular bed, leading to impaired trophism of the nervous tissue [11]. So, L. Yu et al. (2009) found that in patients with DPN (n=60) the level of TNF-α was significantly higher than in patients with diabetes without complications (n=28) (p<0.001) [12]. In a study by J. Doupis et al. (2009) patients with DPN (n=77) had higher levels of C-reactive protein (CRP) (P<0.0001), TNF-α (P<0.05) and fibrinogen (P<0.05) . And in patients with a painful form of neuropathy (n=46), the level of CRP (p<0.01) was higher compared to the group of patients suffering from a painless form of neuropathy [13]. Papanas et al. in their work (2011) showed that patients with DM and DPN (n=64) have significantly higher concentrations of uric acid (P<0.001) and CRP compared with patients with type 2 diabetes without neuropathy (n=66) [14] . In a study by T. Purwata et al. (2011) the level of TNF-α was significantly higher in the group with pain neuropathy (n=59). Statistically significant differences were recorded even within the pain group (mean level of TNF-α 15.24±5.42 pg/ml in patients with moderate pain versus 20.44±10.34 in patients with severe pain) [15]. C. Herder et al. (2013) determined serum concentrations of inflammatory mediators, neurological complaints, and the Michigan neurological symptom score in 1047 Augsburg patients aged 61 to 82 years. Levels of IL-1, IL-6, and IL-18 were positively correlated with Michigan neurological symptom scores. This correlation persisted even after adjusting for waist circumference, hypertension, lipid spectrum, smoking, alcohol consumption, physical activity level, history of heart attacks and strokes, and use of non-steroidal anti-inflammatory drugs [16].

According to the FIELD study, symptoms of DPN were noted in 564 of 9795 patients with type 2 diabetes included in the study. Fenofibrate (Trycor) reduced the incidence of new cases of DPN by 18% compared with the control group. A 40% regression of already diagnosed DPN was shown in the Tricor group [17]. Thus, long-term fenofibrate therapy reduced neuropathy in general and increased the incidence of regression of pre-existing neuropathy.

To quantify the complaints of patients with DPN, the TSS (Total Symptom Score) scale is used, which includes four positive neuropathic symptoms: shooting pain, burning, paresthesia, and numbness in the feet and/or legs (Table 3).

The NIS-LL (Neuropathy Impairment Score of Low Limbs) scale is used to quantify neurological deficit, which gives a fairly objective idea of ​​the severity of nerve fiber damage. Muscle strength is determined by flexion and extension of the hip, knee, ankle, and toes. Normally, the coefficient of muscle strength is 0, a decrease in strength by 25% is 1, by 50% – 2, by 75% – 3, and a coefficient of 4 is already paralysis. Tendon reflexes and the degree of decrease in tactile, pain and vibration sensitivity are also assessed on the NIS-LL scale (0 – normal, 1  – reduced, 2 – absent). It is very important to evaluate the combination of TSS and NIS-LL scores, bearing in mind that the TSS is more placebo dependent.

Studies on the effects of fenofibrate in DPN have shown improvement in the condition of patients on the NIS-LL and TSS scales (Table 4).

DPN can develop into diabetic foot syndrome and lead to lower limb amputations. About 230 amputations are performed every 24 hours due to diabetes. Despite strict measures against reversible factors, about one in ten patients with diabetes will eventually need at least one amputation. In the UKPDS study, a decrease in glycated hemoglobin by 0.9% using intensive glucose control for 10 years did not reduce the frequency of amputations [18]. Glucose control in the UKPDS study over 20 years also did not affect amputation rates [19]. Neither blood pressure control nor cholesterol reduction has been able to prevent the risk of amputations, highlighting the importance of assessing the control of other potential risk factors.

The FIELD trial evaluated the effect of Tricor on amputation rates in patients with diabetes. According to the results of the study, a 46% reduction in the frequency of small non-traumatic amputations was shown compared with placebo (figure).

The effect of fenofibrate therapy on the risk of amputation may be far from that on lipid control, as in multivariate analyses, none of the lipid measures was associated with the risk of amputation. In addition, the Heart Protection Study [20], which randomized 5963 people with DM into simvastatin and placebo groups, showed no significant difference in amputation rates between groups, despite a significant reduction in total cholesterol, LDL concentrations, and small changes in triglycerides and HDL concentrations in the intervention group compared to the control group. This result suggests that the effect of fenofibrate in reducing the risk of amputations is rather not due to the drug’s effect on lipid concentrations and is therefore independent of the difference in statin use between groups in the FIELD study.

Several theoretical models have been proposed regarding the beneficial effects of fenofibrate on the microvascular system. In a randomized placebo-controlled trial, 12-week fenofibrate therapy [21] was accompanied by an improvement in endothelium-dependent vascular reactivity, a decrease in the level of markers of endothelial dysfunction, as well as pro-inflammatory markers, including TNF-α, IL-6 and IL-1β in plasma; another study also demonstrated that fenofibrate therapy was accompanied by a decrease in blood viscosity [22]. In patients with HTH and various signs of MS, fenofibrate improved congestion-mediated vasodilation, increased adiponectin concentrations, and improved insulin sensitivity [23]. The drug may exert its anti-angiogenic effects directly [24] or by reducing ischemia through these actions [21-23]. Fenofibrate also activates AMP kinase in endothelial cells via the peroxisome proliferator-activated receptor α, preventing retinal cell apoptosis [25] and possibly increasing NO synthesis [26]. Fenofibrate may also play a protective role due to the suppression of oxidative stress [27]. Fenofibrate has also been reported to have a neuroprotective effect in rodents [28], which may be particularly important given the key role of neuropathy in relation to the risk of amputation.

Antioxidants, aspirin, statins, and antihypertensives have not been shown to reduce amputations in patients with DM in large trials. Thus, the inclusion of Traycor in the treatment regimen for such patients is rational.

Literature

1. IDF Diabetes Atlas. 6th edition. Available from: http://www.idf.org/diabetesatlas.
2. Dedov I.I., Shestakova M.V., Galstyan G.R. Diabetes. 2016;19(2):104–12.
3. Diagnosis and correction of lipid metabolism disorders in order to prevent and treat atherosclerosis. Russian recommendations. V revision. Moscow, 2012
4. Miselli M.-A., Nora E.D., Passaro A., Tomasi F., Zuliani G. Plasma triglycerides predict ten-years all-cause mortality in outpatients with type 2 diabetes mellitus: a longitudinal observational study . Cardiovasc. Diabetology. 2014;13:135.
5. Hermans M.P., Fruchart J.-C. Reducing residual vascular risk in patients with atherogenic dyslipidemia: where do we go from here? Clin. Lipidol. 2010;5(6):811–26.
6. Berger J.S., McGinn A.P., Howard B.V., Kuller L., Manson J.E., Otvos J., Curb J.D., Eaton C.B., Kaplan R.C., Lynch J.K., Rosenbaum D.M., Wassertheil-Smoller S. Lipid and lipoprotein biomarkers and the risk of ischemic stroke in postmenopausal women. Stroke. 2012;43(4):958–66.
7. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.
8. Brownlee M. The pathobiology of diabetic complications. A unifying mechanism. diabetes. 2005;54:1615–25.
9. Wang X.-M., Lehky T.J., Brell J.M., Dorsey S.G. Discovering cytokines as targets for chemotherapy-induced painful peripheral neuropathy. Cytokine. 2012;59:3–9.
10. Fromont A., De Seze J., Fleury M.C., Maillefert J.F., Moreau T. Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine. 2009;45:55–7.
11. Malik R.A., Newrick P.G., Sharma A.K., Jennings A., Ah-See A.K., Mayhew T.M., Jakubowski J., Boulton A.J., Ward J.D. Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy. Diabetology. 1989;32:92–102.
12. Yu L., Yang X., Hua Z., Xie W. Serum levels of proinflammatory cytokines in diabetic patients with peripheral neuropathic pain and the correlation among them. Zhonghua Yi Xue Za Zhi. 2009;89(7):469–471.
13. Doupis J., Lyons T.E., Wu S., Gnardellis C., Dinh T., Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J.Clin. Endocrinol. Metab. 2009;94(6):2157–63.
14. Papanas N., Katsiki N., Papatheodorou K., Demetriou M., Papazoglou D., Gioka T., et al. Peripheral neuropathy is associated with increased serum levels of uric acid in type 2 diabetes mellitus. Angiology. 2011;62(4):291–5.
15. Purwata T. High TNFalpha plasma levels and macrophages iNOS and TNFalpha expression as risk factors for painful diabetic neuropathy. JPR. 2011;4:169–75.
16. Herder C., Bongaerts B.W.C., Rathmann W., Heier M., Kowall B., Koenig W., Thorand B., Roden M., Meisinger C., Ziegler D. Association of subclinical inflammation with polyneuropathy in the older population : KORA F4 study. Diabetes Care. 2013;36(11):3663–70.
17. Rajamani K., Donoghoe M., et al 78th EAS Congress/Atherosclerosis Supplements 11.2010;2:219-20.
18. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–53.
19. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 2008;359:1577–89.
20. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomized placebo controlled trial. Lancet. 2003;361:2005–16.
21. Ryan K.E., McCance D.R., Powell L., McMahon R., Trimble E.R. Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men. atherosclerosis. 2007;194:e123–30.
22. Rosenson R.S., Helenowski I.B. Fenofibrate abrogates postprandial blood viscosity among hypertriglyceridemia subjects with the metabolic syndrome. Diab. Met. Syndr. Clin. Res. Rev. 2009;3:17–23.
23. Koh K., Han S., Quon M. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care. 2005;28:1419–24.
24. Panigrahy D., Kaipainen A., Huang S., Butterfield C.E., Barnés C.M., Fannon M., Laforme A.M., Chaponis D.M., Folkman J., Kieran M.W. PPAR alpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition. Proc. Natl. Acad. sci. USA. 2008;105:985–90.
25. Kim J., Ahn J.H., Kim J. H., Yu Y.S., Kim H.S., Ha J., Shinn S.H., Oh Y.S. Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway. Exp. Eye Res. 2007;84:886–93.
26. Murakami H., Murakami R., Kambe F., Cao X., Takahashi R., Asai T., Hirai T., Numaguchi Y., Okumura K., Seo H., Murohara T. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC. Biochem. Biophys. Res. commun. 2006;341:973–8.
27. Losada M., Alio J.L. Malondialdehyde serum concentration in type 1 diabetic with and without retinopathy. Doc. Ophthalmol. 1997;93:223–9.
28. Deplanque D., Gelé P., Pétrault O., Six I., Furman C., Bouly M., Nion S., Dupuis B., Leys D., Fruchart J.C., Cecchelli R., Staels B., Duriez P., Bordet R. Peroxisome proliferator-activated receptor-alpha activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment. J. Neurosci. 2003;23:6264–71.
29. Kornitzer M., Dramax M., Vanderbrock M.D. et al. Efficacy and tolerance of 200 mg micronised fenofibrate alministered over a 6-month period in hyperlipidemic patients: an open Belgian multicenter study. atherosclerosis. 1994;110 (Suppl):S49–S54.
30. Kirchgassler K.U., Schmitz H., Bach G. Effectivenes and tolerability of 12-week treatment with micronized fenofibrate 200 mg in a drug – monitoring program involving 9884 patients with dyslipidemia. Clin. Drug Invest. 1998;15:197–204.
31. Poulter N. The impact of micronized fenofibrate on lipid subfractions and on reaching HDL-target levels in 7098 patients with dyslipidemia. Brit. J. Cardiol. 1999;6:682–5.
32. Frick M.H., Elo M.O., Haapa K. et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle aged men with dyslipidemia. Safety of treatment, Changes in risk factors and incidence of coronary heart disease. N. Engl. J. Med. 1987;317:1237–45.
33. Rubins H.B., Robins S.J., Collins D., Fye C.L., Anderson J.W., Elam M.B., Faas F.H., Linares E., Schaefer E.J., Schectman G., Wilt T.J., Wittes J. Gemfibrosil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N. Engl. J. Med. 1999;341:410–8.
34. The BIP Study group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. The bezafibrate infarction prevention (BIP) study. circulation. 2000;102:21–7.
35. Erricsson C.G., Hamsted A., Nilsson J. et al. Angiographic assessment of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet. 1996;347:849–53.
36. Bunte T., Hahmann H.W., Hellwig N. et al. Effects of fenofibrate on angiographically examined coronary atherosclerosis and left ventricular function in hypercholesterolemic patients. atherosclerosis. 1993;98:127–38.

Authors / Correspondence

Tatyana Yulyevna Demidova, MD, professor; Professor of the Department of Endocrinology, SBEE DPO “Russian Medical Academy of Postgraduate Education”. Address: 125315, Moscow, st. Clock, 20.
Phone: (495) 490-42-41. E-mail: t. [email protected]

Drozdova Irina Nikolaevna, post-graduate student of the Department of Endocrinology, SBEI DPO “Russian Medical Academy of Postgraduate Education”. Address: 125315, Moscow, st. Clock, 20. Phone: (495) 490-42-41.
E-mail: [email protected]

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Fenofibrate, oral tablet – Drink-Drink

Key features of fenofibrate

90 003 Fenofibrate oral tablets are available as branded products and as generics. Brand names: Fenoglide, Tricor and Triglide.
1. Fenofibrate is available in two forms: oral tablet and oral capsule.
2. Fenofibrate oral tablets are used to treat high cholesterol. It is mainly used to treat severe high triglycerides (a type of bad cholesterol).

Important warnings

Serious liver damage warning: Fenofibrate may cause serious liver damage. This may occur during the first few weeks of treatment or after several months of treatment. This may require a liver transplant and can be life-threatening. Symptoms of liver damage include dark urine, upset stomach or abdominal pain, muscle pain, feeling tired, or yellowing of the skin or eyes. Contact your doctor immediately if you experience any of these symptoms.

Severe Allergy Warning: Fenofibrate may cause severe allergic reactions. These can include anaphylaxis and angioedema (edema) and can be life-threatening. Some reactions may occur days or weeks after starting this drug. Possible reactions include Stevens-Johnson syndrome, toxic epidermal necrolysis, and a drug reaction with eosinophilia and systemic symptoms, a problem called DRESS. Call number 911 or go to the emergency room immediately if you have a rash, swelling of your face, tongue or throat, or trouble breathing.

Serious muscle problem warning: This medicine can cause serious muscle problems, including myopathy, which can cause muscle pain, tenderness, or weakness. Myopathy can also lead to rhabdomyolysis. This condition causes muscle breakdown and can lead to kidney damage and even death. If you notice unusual muscle pain or weakness, call your doctor right away, especially if you feel more tired than usual or have a fever. Your doctor may decide to stop taking this medicine. Call your doctor right away if muscle problems persist after you stop taking this drug.

What is fenofibrate?

Fenofibrate is a prescription drug. It comes in two forms: an oral tablet and an oral capsule.

Oral tablets are available as the brand name Fenoglide, Tricor, and Triglide. It is also available as a generic drug. Generic drugs usually cost less than their brand-name versions. In some cases, they may not be available in all dosages and forms as brand-name drugs.

Fenofibrate may be used as part of combination therapy. This means that you may need to take it with other cholesterol medications such as statins.

Why it is used

Fenofibrate is used to improve cholesterol levels for three types of cholesterol problems:

• Mixed dyslipidemia: high LDL cholesterol (bad) and triglycerides and low HDL cholesterol (good)

90 003 Severe hypertriglyceridemia : very high triglycerides

• Primary hypercholesterolemia: very high LDL cholesterol

Fenofibrate helps reduce high levels of bad cholesterol, mainly triglycerides. It also helps increase HDL (good) cholesterol levels.

How does it work?

Fenofibrate belongs to a class of drugs called fibric acid derivatives. A drug class is a group of drugs that work in a similar way. These drugs are often used to treat these conditions.

Fenofibrate works by increasing the breakdown and removal of bad cholesterol from your body. This helps reduce the risk of cholesterol building up in the blood vessels and causing serious health problems such as a heart attack or stroke.

Fenofibrate side effects

Fenofibrate oral tablets may cause mild or serious side effects. The following list lists some of the key side effects you may experience while taking fenofibrate. This list does not include all possible side effects.

For more information about the possible side effects of fenofibrate or advice on how to manage an unpleasant side effect, talk to your doctor or pharmacist.

More common side effects

More common side effects that may occur with fenofibrate use include:

If these effects are mild, they may disappear within a few days or a few weeks. If they get worse or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have any serious side effects. Call 911 if your symptoms are life threatening or if you think you need emergency medical attention. Serious side effects and their symptoms may include the following:

• Liver problems. Symptoms may include:
  • yellowing of the skin or whites of the eyes
  • dark urine
  • abdominal pain (in the abdomen)
  • decreased appetite
  • unexplained or unusual weakness
• Severe allergic reactions. Symptoms may include:
  • swelling of the face, eyes, lips, tongue, hands, arms, legs, ankles, or lower legs
  • trouble breathing or swallowing
  • rash
  • peeling or blistering of the skin

900 09

Fenofibrate may interact with other medicines.

Fenofibrate oral tablet may interact with several other medicines. Different interactions can cause different effects. For example, some of them may affect the effectiveness of the drug, while others may increase the side effects.

The following is a list of medicines that may interact with fenofibrate. This list does not contain all drugs that can interact with fenofibrate.

Be sure to tell your doctor and pharmacist about all prescription, over-the-counter and other medicines you are taking before taking fenofibrate. Also tell them about any vitamins, herbs and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Blood thinner

Warfarin is a drug used to thin the blood. Taking it with fenofibrate increases the risk of bleeding. If you are taking these drugs together, your doctor may do more blood tests or change your warfarin dosage.

Cholesterol drugs

Taking fenofibrate with certain cholesterol medicines called bile acid sequestrants can make it difficult for your body to absorb fenofibrate. To prevent this, fenofibrate should be taken 1 hour before taking a bile acid sequestrant or 4 to 6 hours after taking it. Examples of bile acid sequestrants include:

• cholestyramine
• colesevelam
• colestipol

In addition, taking fenofibrate with cholesterol medicines called statins increases the risk of rhabdomyolysis. This is a serious condition that destroys muscles. Examples of statins include:

• atorvastatin
• fluvastatin
• lovastatin
• pitavastatin
• pravastatin
• rosuvastatin

9000 3 simvastatin

Diabetes drugs

Taking fenofibrate with certain diabetes medicines called sulfonylurea increases the risk of low blood sugar. Examples of such drugs include:

• glimepiride
• glipizide
• glibenclamide

Gout medication

Colchicine is a drug used to treat gout . Taking it with fenofibrate increases the risk of muscle pain.

Immunosuppressants

Taking fenofibrate with certain drugs that suppress the body’s immune response can increase the level of fenofibrate in the body. This increases the risk of side effects from fenofibrate. Examples of such drugs include:

• cyclosporine
• tacrolimus

How to take fenofibrate

The amount of fenofibrate your doctor prescribes will depend on several factors. This includes:

• Type and the severity of the condition for which you use phenofibrat
• Your age
• Form of the phenofibrat, which you take
• Other medical conditions that you may have

, your doctor starts with low dosage and adjusts it over time to reach your desired dosage. Ultimately, they will prescribe the lowest dosage that provides the desired effect.

The following information describes commonly used or recommended dosages. However, be sure to take the dose your doctor has prescribed for you. Your doctor will determine the best dosage for your needs.

Drug Forms and Strengths

Generic: Fenofibrate

• Form: oral tablet
• Strengths: 40mg, 48mg , 54 mg, 107 mg, 120 mg, 145 mg, 160 mg

Brand: Fenoglide

• Form: oral tablet
• Strengths: 40mg, 120mg

9017 8 Brand: Tricor

• Shape: oral tablet
• Strengths: 48mg, 145mg

Brand: Triglide

• Form: oral tablet
• Strength: 160mg 9 0004

Dosage for primary hypercholesterolemia and mixed dyslipidemia

Adult dosage (age 18 and over)

• 120 mg per day.
• 145 mg per day.
• 160 mg per day.
• 120–160 mg per day, depending on the generic prescribed.

Dosage for children (age 0-17 years)

The use of this drug in children has not been studied. It should not be used by people under 18 years of age.

Senior dose (age 65+)

Older people’s kidneys may not work as well as they used to. This can cause your body to process medications, including fenofibrate, more slowly. As a result, more of the drug remains in the body for a longer time. This increases the risk of side effects.

Your doctor may give you a lower dose or a different dosing schedule. This may help prevent excessive buildup of this drug in the body.

Dosage for severe hypertriglyceridemia

Adult dosage (age 18 and over)

• 40-120 mg per day.
• 48–145 mg per day.
• 160 mg per day.
• 40–120 mg per day or 48–160 mg per day, depending on the generic prescribed.

Dosage for children (age 0-17 years)

The use of this drug in children has not been studied. It should not be used by people under 18 years of age.

Senior dose (age 65+)

Older people’s kidneys may not work as well as they used to. This can cause your body to process medications, including fenofibrate, more slowly. As a result, more of the drug remains in the body for a longer time. This increases the risk of side effects.

Your doctor may give you a lower dose or a different dosing schedule. This may help prevent excessive buildup of this drug in the body.

Special dosage recommendations

For people with kidney disease: If you have mild kidney disease, you may need a lower dose of fenofibrate.

Fenofibrate warnings

This drug has several warnings.

Muscle Pain Warning

This drug increases the risk of muscle pain and a serious muscle problem called rhabdomyolysis. The risk is higher if you take the drug along with statins.

Liver damage warning

Fenofibrate may cause abnormal liver function test results. These abnormal results may indicate liver damage. This drug can also cause other liver damage and inflammation after years of use.

Gallstone warning

Fenofibrate increases the risk of gallstones.

Pancreatitis Warning

Fenofibrate increases the risk of pancreatitis (inflammation of the pancreas).

Severe Allergy Warning

Fenofibrate may cause severe allergic reactions. These can include anaphylaxis and angioedema (edema) and can be life-threatening. Some reactions may occur days or weeks after starting this drug. These include Stevens-Johnson syndrome, toxic epidermal necrolysis, and a drug reaction with eosinophilia and systemic symptoms. This last type of reaction is often referred to as DRESS.

Symptoms of a severe reaction may include:

• rash, especially if it comes on suddenly
• peeling or blistering of the skin
• nausea and vomiting
• difficulty breathing
• itching

9 0003 urticaria

If you get these symptoms , call 911 or go to the nearest emergency room.

Do not take this drug again if you have ever had an allergic reaction to it. Repeated use may be fatal (cause death).

Warnings for people with certain medical conditions

For people with liver disease: Fenofibrate may cause liver problems that can lead to liver failure. Tell your doctor if you have a history of liver disease. Your doctor can tell you if fenofibrate is safe for you. If you have active liver disease, you should not take fenofibrate.

For people with kidney disease: Fenofibrate may cause abnormal results on kidney function tests. These changes are usually temporary and do no harm. To be safe, your doctor may monitor your kidney function more frequently. If you have severe kidney disease, you should not take fenofibrate.

Warnings for other groups

For pregnant women: There have not been sufficient human studies to show whether fenofibrate poses a risk to the human fetus. Animal studies have shown a risk to the fetus when the mother takes the drug. However, animal studies do not always predict how people will react.

Talk to your doctor if you are pregnant or planning to become pregnant. This drug should only be used if the potential benefit justifies the potential risk.

If you become pregnant while taking this drug, call your doctor right away.

For breastfeeding women: Fenofibrate may pass into breast milk and cause side effects in a breastfed infant. Talk to your doctor if you are breastfeeding. You may need to decide whether to stop breastfeeding or stop taking this medication.

Take as directed

Fenofibrate oral tablets are used for long-term treatment. It comes with risks if you don’t take it as prescribed.

If you suddenly stop taking a drug or don’t take it at all: Your cholesterol levels may not be controlled. This raises the risk of serious health problems such as heart disease, heart attack or stroke.

If you miss doses or don’t take your medicine as scheduled: Your medication may not work or may not work at all. For this drug to work well, there must be a certain amount in your body at all times.

If you take too much: You may have dangerous levels of the drug. Overdose symptoms with this drug may include:

• Headache
• back pain
• nausea
• muscle pain
• diarrhea
• cold
• Upper respiratory tract infection

Call your doctor or local poison control center if you think you have taken too much. If you have severe symptoms, call 911 or go to the nearest emergency room.

What to do if you miss an appointment: Take your dose as soon as you remember. But if you only remember a few hours before your next scheduled dose, take only one dose. Never try to catch up by taking two doses at once. This can lead to dangerous side effects.

How to know if the drug will work: Cholesterol levels should improve. You won’t feel the effects of fenofibrate, but your doctor will check your cholesterol levels with blood tests. Your doctor may adjust your dosage based on the results of these tests.

Important Considerations When Taking Fenofibrate

Keep these considerations in mind if your doctor prescribes fenofibrate for you.

General

• Fenofibrate tablets should be taken with food. This can help increase the amount of the drug your body absorbs.
• Take this drug at the time your doctor tells you to.
• Do not cut or crush tablets.

Memory

• Store Fenoglide and Tricor tablets at room temperature, 59°F to 86°F (15°C to 30°C).
• Store generic fenofibrate tablets and Triglide tablets at 68°F to 77°F (20°C to 25°C).
• Do not store these medicines in damp or damp areas such as bathrooms.
• Keep Triglide in a moisture-proof container until you are ready to take it.

Refills

The prescription for this medicine is refillable. You do not need a new prescription to refill this medicine. Your doctor will write down the number of additives allowed in your prescription.

Travel

If you are traveling with medication:

• Carry your medication with you at all times. During the flight, never put it in your checked baggage. Keep it in your hand luggage.
• Don’t worry about the X-ray machines at the airport. They cannot harm your medicine.
• You may need to show airport staff the pharmacy label for your medications. Always carry the original packaging with the prescription label with you.
• Do not put this medicine in the glove compartment of your car or leave it in your car. Avoid this in very hot or very cold weather.

Clinical monitoring

Your doctor will monitor your health while you are taking this drug. They will do blood tests to make sure your cholesterol levels are in the range the doctor thinks is best for you. The tests will also show if your medicine is working.

In addition, your doctor will likely monitor you for certain health problems. This may help you stay safe while taking this drug. These problems include:

• Kidney function. Blood tests can check how well your kidneys are working. If your kidneys are not working well, your doctor may lower your dosage of this drug.
• Liver function. Blood tests can check how well your liver is working. If your tests are not normal, it could mean fenofibrate is causing damage to your liver. Your doctor may switch you to another medicine.
• Lipid levels. Blood tests can check how well this drug lowers cholesterol and triglycerides. Your doctor may change your therapy based on these results.

Your Diet

In addition to taking this drug, you should eat a heart-healthy diet to control your cholesterol. Talk to your doctor about a diet that’s right for you.

Availability

Not every pharmacy stocks this drug. When you get a prescription, be sure to call ahead to make sure your pharmacy has it.

Prior Authorization

Many insurance companies require prior authorization for this drug. This means that your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.

Are there alternatives?

There are other medicines available to treat your condition. Some may suit you better than others. Talk to your doctor about other drug options that may help you.

Registration data: Drink-Drink has made every effort to ensure that all information is accurate, complete and up to date. However, this article should not be used as a substitute for the knowledge and experience of a licensed healthcare professional. You should always check with your doctor or other healthcare professional before taking any medication. The drug information contained in this document is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or side effects.