Search

Fenofibrate (FF) has previously been shown to induce hepatocellular neoplasia in a conventional mouse bioassay (NDA 1993), but there has been no report to examine the carcinogenic susceptibility of rasH2 mice to this chemical. In the present study, male rasH2 mice were subjected to a two-thirds partial hepatectomy (PH), followed by an N-diethylnitrosamine (DEN) initiation twenty-four hours after PH, and given a diet containing 0, 1200, or 2400 ppm FF for seven weeks. The incidences of preneoplastic foci were significantly increased in mice from the FF-treated groups. Immunohistochemistry revealed that significant increases in proliferating cell nuclear antigen (PCNA)-positive cells and cytokeratin 8/18 positive foci were observed in FF-treated groups. In addition, the transgene and several downstream molecules such as c- myc, c- jun, activating transcription factor 3 (ATF3), and cyclin D1 were overexpressed in these groups. These results suggest that the hepatocarcinogenic activity of rasH2 mice to FF can be detected in this hepatocarcinogenesis model and that up-regulation of genes for the ras/MAPK pathway and cell cycle was probably involved in the hepatocarcinogenic mechanism of rasH2 mice.

Fenofibrate, a fibric acid derivative, is used as adjunctive therapy with diet for treatment of hyperlipidemia. Side effects include gastrointestinal complaints and, rarely, elevations in liver function tests. According to the drug's package insert, elevations in serum creatinine may occur; although, no postmarketing case reports of fenofibrate-induced elevations in serum creatinine are on file with the manufacturer. Fenofibrate was the probable cause of elevations in serum creatinine concentrations in six patients at our clinic. As the implications of these elevations may be serious, routine serum creatinine monitoring is recommended at baseline and 1-2 months after starting fenofibrate.

Fibrates are used to manage mixed dyslipidemia. However, these drugs have the potential risk of inducing rhabdomyolysis. This paper gives an overview of the literature on rhabdomyolysis associated with fibrate therapy.We reported a case of rhabdomyolysis induced by fenofibrate and reviewed the published rhabdomyolysis cases associated with fibrate therapy.Seventy-six published rhabdomyolysis cases associated with fibrates were evaluated, and a nondiabetic, nonhypertensive patient who presented with rhabdomyolysis caused by fenofibrate was reported. The onset time of the reaction varied between 36 h and 6 months. Gemfibrozil was the most frequent agent associated with rhabdomyolysis, followed by bezafibrate, fenofibrate, ciprofibrate, and clofibrate. Twenty-three cases were associated with fibrate monotherapy and 54 with fibrate therapy combined with statins or other drugs potentially interacting with fibrates. Sixteen cases had chronic renal failure before fibrate therapy, and 6 had hypothyroidism. Fifty-four complicated acute renal failure. After discontinuation of the fibrates and hydration, most patients recovered.Chronic renal failure may be a risk factor for rhabdomyolysis associated with fibrates. Although rhabdomyolysis usually occurred when fibrates were combined with statins, a well-known class of agents that potentially induce rhabdomyolysis, precautions against serious adverse effects should also be taken with fibrate monotherapy.

The aim of this study was to evaluate the possibility of cross-reactivity between ketoprofen, fenofibrate and benzophenones because of their structural similarities. Seven patients presenting photodermatitis from ketoprofen underwent patch and photopatch tests. Ketoprofen, fenofibrate, benzophenone 3, benzophenone 10, benzophenone 4, personal medications and topical creams were tested. All patients had positive patch or photopatch tests to ketoprofen and fenofibrate, four patients had positive UVA photopatch tests to benzophenone 3, and two to benzophenone 10. Patients presenting photosensitization to ketoprofen may also have cross-reactivity to fenofibrate and some benzophenones.

During the past 20 years, fibric acid derivatives have been the drugs most commonly used in the treatment of hyperlipidemia. Among them, fenofibrate is the most frequently prescribed. 1 Side effects of these drags are mainly gastrointestinal, but skin manifestations also occur in approximately 2% of patients. 2-6 Only a few instances of photosensitivity have been reported. 7-11 In these reports, the results of photopatch testing have been variable. 8, 9 Thus systemic photochallenge may be a more appropriate test to determine fenofabrate-induced photosensitivity. W e describe three patients in whom photosensitivity caused by fenofibrate was proved by systemic photochallenge.