Benzafibrate

Benzafibrate is a lipid-lowering agent and belongs to the substance class of fibrates.

Significance: In contrast to statins, fibrates have only a minor effect on the LDL-C value, which plays a decisive role in cardiovascular risk, and have not been shown to improve prognosis.

Fibrates are therefore only used in very few indications, predominantly in cases of elevated triglyceride levels, and are used less frequently than satins and other lipid-lowering drugs. In addition, fibrates are very difficult to combine with other lipid-lowering drugs such as statins due to their complex WW profile, which further limits their applicability.

Mechanism of action: Benzafibrate increases the activity of the triglyceride lipases (lipoprotein lipase and hepatic lipoprotein lipase) involved in the breakdown of triglyceride-rich lipoproteins.
In the course of the accelerated breakdown of triglyceride-rich lipoproteins (chylomicrons, VLDL), HDL precursors are formed, which can explain the increase in HDL concentration. In addition, benzafibrate reduces cholesterol biosynthesis, while at the same time stimulating LDL receptor-mediated lipoprotein degradation.

Benzafibrate lowers triglycerides (VLDL and, to a lesser extent, LDL-C) and increases HDL.

Bezafibrate is also said to have an effect on thrombogenic factors and reduce platelet aggregation, increased fibrinogen levels and blood viscosity.

There is evidence that treatment with fibrates reduces the incidence of coronary heart disease events. However, there is no evidence of a positive effect on all-cause mortality in the primary or secondary prevention of cardiovascular disease.

Absorption and distribution:Bezafibrate is rapidly and almost completely absorbed. Bioavailability of the slow-release form is approx. 70% and thus lower than for the non-released form. Peak plasma levels reached after 1 - 2 hours. Plasma protein binding approx. 94 - 96 %.

Metabolization and elimination: rapid and almost exclusive elimination via the kidneys (only partially metabolized); approx. 95% eliminated within 48 hours via the kidneys and only approx. 3 % via the intestines.

Approx. 50 % of the administered dose appears in the urine as unchanged bezafibrate, 20 % in the form of glucuronides. The average elimination half-life is 1 - 2 hours.

Elimination is delayed in patients with renal insufficiency. Dose reduction is necessary to avoid accumulation and toxic effects! The elimination half-life also increases with decreasing GFR.
Elimination may also be delayed in elderly patients with impaired liver function. Use is contraindicated in liver disease (with the exception of fatty liver).
Bezafibrate cannot be dialyzed (cuprophane filter).

Therapy according to guidelines always in conjunction with lifestyle changes.

In hyperlipidemia only second-line therapy, as first-line therapy statins due to better proven efficacy and proven improvement in prognosis! in particular with concomitant hypercholesterolemia!

for hypetriglyceridemia: only second-line therapy in this case too; only to be considered for very high triglyceride levels with risk of pancreatitis.

First-line therapy for hypertriglyceridemia is therapy of the underlying disease, as it is often secondary, e.g. in diabetes mellitus, otherwise weight loss, dietary changes with avoidance of saturated fats (animal fats), exercise, possibly alcohol reduction or abstinence and possibly statins for primary or secondary prevention according to risk profile and LDL-C target value.

The problem is that fibrates are difficult to combine with statins, as the risk of dangerous severe myopathies and rhabdomyolysis is increased; observe contraindications and WW of the individual statins and other concomitant medication!

For use in adults only; no studies/data available on children and adolescents

For further information, see the technical information of the respective preparation!

For further information on the indication, see the applicable guidelines!

frequently or occasionally: loss of appetite, feeling of fullness;

Generally, an increase in transaminases, cholestasis and gallstone formation are possible;

discontinue if transaminases increase ≥3 times normal, as well as signs of cholestasis (jaundice, brown coloration of urine)!

rarely: pancreatitis

occasionally: headache, dizziness, hypersensitivity reactions, pruritus, urticaria, photoallergic or phototoxic reactions with erythema, pruritus, blistering or lichenoid changes, thrombocytopenic purpura, hair loss

occasionally: myotoxicity with muscle pain, muscle weakness and muscle cramps (determination of CK!
)

very rare: considerable increase in CK with clinical picture of drug-induced rhabdomyolysis (often due to excessive dosage, WW or accumulation in renal insufficiency) if rhabdomyolysis is suspected, discontinue therapy with bezafibrate immediately and monitor renal function carefully!

very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
(discontinue immediately and initiate appropriate treatment measures!)

Effect of antidibetics (oral and insulin) may be increased (risk of hypoglycemia!)

Effect of coumarins may be increased (risk of bleeding!)

Bezafibrate, like other fibrates, should not be combined with statins (HMG-CoA reductase inhibitors) due to the risk of rhabdomyolysis (see also contraindications).

Bezafibrate must not be taken at the same time as perhexiline hydrogen maleate, MAO inhibitors (Federal Office for Safety in Health Care BASG, Austria) (risk of hepatotoxicity).

Danger of WW also with immunosuppressants (transplantation) and protease inhibitors! Close monitoring (especially kidney function) and discontinuation if necessary!

Colestyramine impairs absorption, therefore take 2 hours apart!

Note displacement from plasma protein binding!

Complex WW profile Further WW must be clarified in advance in each individual case.

• Hypersensitivity to the active substance or ingredients
• Liver diseases (with the exception of fatty liver, a frequent concomitant symptom of hypertriglyceridemia)
• Gallbladder disease with or without cholelithiasis (as the possibility of liver involvement cannot be ruled out)
• known photoallergic or phototoxic reactions during treatment with fibrates
• patients undergoing dialysis
• severe renal dysfunction with serum creatinine levels above 6 mg/dl or a creatinine clearance below 15 ml/min.
• Bezafibrate must not be taken at the same time as perhexiline hydrogen maleate, MAO inhibitors (Federal Office for Safety in Health Care BASG) (risk of hepatotoxicity).
• Pregnancy and breastfeeding

Very strict indication for combination with statins; contraindicated with some statins and only limited use with others! Use should be limited to exceptions with severe hyperlipidemia, where there is no alternative and no disease with increased NW risk! Do not use simultaneously in patients with diseases that increase the risk of myopathy, such as renal dysfunction, severe infections, trauma, surgery, hormonal and electrolyte imbalances; there is a risk of rhabdomyolysis!

For further information see specialist information!