Hyperlipidemia fibrates

Familial combined hyperlipidemia may respond better to a fibrate and a statin than to a fibrate and a BAR. 

The fibrates are mainly used to treat two hyperlipi-demias, familial hypertriglyceridemia (type IV) and dysbetalipoproteinemia (type III). They are also useful in the treatment of hypertriglyceridemia associated with type II diabetes (secondary hyperlipidemia). The fibrates are the drugs of choice in treating hypertriglyceridemias, particularly those associated with low levels of HDL cholesterol. The fibrates additionally appear to... 

Fibrate monotherapy of hyperlipidemia may predispose to rhabdomyolysis with acute renal insufficiency. Patients using fibrates should be cautioned regarding strenuous exertion, dehydration, and the need for prompt evaluation of myalgia. 

Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Didangelos TP, Carina MV, Kranitsas DF, Kontopoulos AG. Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia. Am J Cardiol 1997 80(5) 608-13. 

Although it is not exactly clear how much these agents can reduce the risk of a major cardiac event (e.g., infarction, stroke), these drugs will probably remain the first choice for people with certain hyper-lipidemias (e.g., increased triglycerides). These drugs are likewise advocated for mixed hyperlipidemias that are common in metabolic disorders such as type 2 diabetes mellitus (see Chapter 32).32,141 Certain fibrates can be used with other drugs, such as statins, to provide more comprehensive pharmacologic control of certain lipid disorders.30,147... 

Fazio S, Linton MF. The role of fibrates in managing hyperlipidemia mechanisms of action and clinical efficacy. Curr Atheroscler Rep. 2004 6 148-157. 

Indications Hyperlipidemia Category Fibrate Lipid regulator Half-life 1.5 hours... 

Trade names Abitrate Atromid-S Claripex Col Lipavlon Novo-Fibrate Regelan N Skleromexe Indications Type III hyperlipidemia Category Fibrate... 

Trade names Bolutol Decrelip Fibrocit Gemlipid Gen-Fibro Gevilon Uno Jezil Lipur Lopid (Pfizer) Nu-Gemfibrozil Indications Hyperlipidemia Category Fibrate Lipid regulator Half-life 1.5 hours... 

However, it must be said that most of the literature considered in this chapter refers to experimental work performed with cell lines or in vivo by means of rodent models. Both PPARot and SREBP-lc are very attractive drug targets. Therefore, it would be of crucial interest to document their respective gender and species-specificity. PPARot activators such as fibrates are currently widely prescribed drugs for human hyperlipidemia. To our knowledge, there is no current use of drugs targeting SREBPlc. 

Renal failure is a relative contraindication to the use of fibric acid agents, as is hepatic dysfunction. Combined statin-fibrate therapy should be avoided in patients with compromised renal function. Gemfibrozil should be used with caution and at a reduced dosage to treat the hyperlipidemia of renal failure. Fibrates should not be used by children or pregnant women. 

Fibrates are approved to treat hypertriglyceridemia and familial combined hyperlipidemia (Fredrickson s type lla, lib, IV, and V) (Table 30.2) in patients who are at risk of pancreatitis and have not responded to dietary adjustments or in patients who are at risk of CHD and have not responded to weight loss, dietary adjustments, and other pharmacological treatment. They can be used either alone or in combination with niacin, bile acid sequestrants, or FlMGRIs. If used with bile acid sequestrants, fibrates must be taken either 1 hour before or 4 to 6 hours after the sequestrant. As discussed previously and reemphasized below, caution should be used it fibrates are combined with HMGRIs. Fibrates are not effective in the treatment of hypertriglyceridemia associated solely to elevated chylomicron levels (Fredrickson s type I). 

Interest in fenofibrate has re-emerged with the near demise of gemfibrozil in some countries, once it became apparent that a statin+fenofibrate combination was highly likely to be safe. It is currently by far the preferred fibrate for the management of hypertriglyceridemia or in combination with a statin for treating combined hyperlipidemia. Different studies with a variety of statins have uniformly found no greater incidence of serious adverse reactions when fenofibrate is added compared with placebo. 

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