Fibrates

Fibrates, also known as PPAR-alpha agonists (PPAR: peroxisome proliferator-activated receptors), are substances that are used as lipid-lowering agents.

Significance: In contrast to statins, fibrates have only a minor effect on LDL-C levels, which play 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: Main mechanism of action is the activation of the PPAR alpha receptor and increase in activity of lipoprotein lipase, as well as accelerated degradation of LDL and triglycerides (but also increased metabolism of VLDL to LDL, therefore LDL increase in hypertriglyceridemia).

LDL-C reduction: 10-20%
TG (triglyceride) reduction: 20-40%
HDL increase: 5-20%

Not all the effects of fibrates are fully known.

Overall, fibrates have only a moderate effect and, unlike statins, have not been shown to improve prognosis. Therefore, they are only of secondary importance in the treatment of hyperlipidemia, mainly in the treatment of hypertriglyceridemia.

Pharmacokinetics vary for individual preparations.

Absorption: good oral absorption, which is improved by taking it close to food.

high plasma protein binding; it should be noted that other drugs can be displaced from their plasma protein binding by fibrates and that the effect of fibrates can be enhanced in hypoalbuminemia (NW, WW!)

Metabolization: mainly in the liver, including glucuronidation (WW); only partially known about which enzyme systems and which transporters are involved, therefore complex and sometimes difficult to assess WW profile and risk of NW.

Elimination: kidney, bile or intestine

Please note in particular: contraindications in case of impaired liver function and biliary tract diseases, as well as GFR-adapted dose restrictions in case of impaired renal function and contraindications in case of severe and terminal renal insufficiency (≤30 or ≤15ml/min) and dialysis.

See also individual substances and technical information for the respective preparation.

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! especially in the case of 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 often secondary e.g. diabetes mellitus, in addition 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 can only be poorly combined with statins, as the risk of dangerous severe myopathies is increased; note the contraindications and WW of the individual statins and other concomitant medication!

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

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

• orally, capsules or tablets
• usually taken 3 times a day with food; prolonged-release preparations also once a day.
• Dosage depends on the respective substance and individual indication
• If administered at the same time as other drugs (anion exchange resins), time intervals between doses may need to be observed!
• Simultaneous administration of statins should be avoided (both substances have a complex WW profile and similar NW, which mutually increase the risk); if necessary, only if strictly indicated, if there is no increased risk of NW and taking into account further restrictions in individual cases (contraindications and WW)!
• See also individual substances and technical information on the respective preparation.

Complex WW profile that is not fully known.

e.g. statins, cyclosporin A, nicotinic acid derivatives,
Oral anticoagulants
Antidiabetics
Antacids, colestipol, colestyramine

Fibrates displace other drugs bound to albumin from their plasma protein binding, so that their plasma concentration can be increased and their effect enhanced! Details should be clarified separately for each substance!

This is only a selection. See also individual substances and technical information of the respective preparation for further information.

1. Karow T, Lang-Roth R (2024): General and special pharmacology 32nd ed. 2024/25.