Rosuvastatin Fenofibrate

Fibrates are being combined with statins to expand their potential in the dyslipidemia market. A recent clinical study examined the effects of rosuvastatin (10) and fenofibrate as mono and combination therapy in hyperlipidemic diabetic patients [43]. In late 2006, large scale Phase III clinical trials of rosuvastatin in combination with a next-generation fibrate, ABT 335, were initiated for evaluation of safety and efficacy in patients with mixed dyslipidemia. 

Rare adverse effects of fibrates include rashes, gastrointestinal symptoms, myopathy, arrhythmias, hypokalemia, and high blood levels of aminotransferases or alkaline phosphatase. A few patients show decreases in white blood count or hematocrit. Both agents potentiate the action of coumarin and indanedione anticoagulants, and doses of these agents should be adjusted. Rhabdomyolysis has occurred rarely. Risk of myopathy increases when fibrates are given with reductase inhibitors. The use of fenofibrate with rosuvastatin appears to minimize this risk. Fibrates should be avoided in patients with hepatic or renal dysfunction. There appears to be a modest increase in the risk of cholesterol gallstones. 

Fenofibrate appears to be complementary with certain statins in the treatment of familial combined hyperlipoproteinemia and other conditions involving elevations of both LDL and VLDL. The combination of fenofibrate with rosuvastatin is particularly effective. Some other statins may interact unfavorably owing to effects on cytochrome P450 metabolism. 

In addition to these newer agents, there are currently three fibrate-based combinations with HMG-CoA reductase inhibitors in clinical trials. In phase III, Sciele has fenofibrate/pravastatin combination and AstraZeneca and Abbott have rosuvastatin/choline fenofibrate (ABT335), while in phase II, Life Cycle Pharma have atorvastatin / fenofibrate. 

A 7-day course of fenofibrate 67 mg three times daily and rosuvastatin 10 mg daily resulted in only minor changes in fenofibric acid and rosuvastatin exposure in 14 healthy subjects, when compared with either drug given alone. ... 

Martin PD, Dane AL, Schneck DW, Warwick MJ. An open-label, randomized, diree-way crossover ttial of the effect of coadministration of rosuvastatin and fenofibrate on die pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin Ther(2003) 25, 459-71. 

Other drags that suppress hver CYP2C11 and CYP3A2 levels include cyclosporine [203, 204] and chloramphenicol [205], although the latter effects are strain dependent and are associated with a modest reduction in plasma levels of thyroxine but not testosterone [205]. GH does not appear to play a role in the suppression of CYP2C11 and CYP3A2 by cyclosporine, which does not alter the plasma GH peak amplitude, niunber, or duration [206]. Phenobarbital [24, 207, 208], dexa-methasone [28], 5-fluoroiuacil [209], doxorubicin [210], fenofibrate [211], rosuvastatin [212],... 

Combination studies In an open extension of a phase III study, in which fenofibrate 135 mg/day was combined with either simvastatin 40 mg/day or rosuvastatin 20 mg/day or atorvastatin 40 mg/day, 287 patients completed the 2-year study [11 ]. There were no cases of rhabdomyolysis and the discontinuation rate due to adverse reactions was 2.9%, with no differences between the three treatments. None of the adverse events was considered serious they generally occurred early during treatment and the most common were myalgia (2.9%), muscle spasms (3.9%), and increased creatine kinase activity (3.5%), the latter being highest with the rosuvastatin combination. 

The authors of a major review of rosuvastatin concluded that its adverse reaction profile resembles that of other commonly used statins [34 ]. Increments in fiver enzymes are in most cases minor and of minimal concern, renal dysfunction is quite uncommon, myopathy is unusual, and rhab-domyolysis is rare. Interactions with other drugs are fisted but no new information given. Combinations with fenofibrate, omega-3 fatty acids, ezetimibe, rifampicin, and clopidogrel appear to be safe. 

A combination therapy of rosuvastatin (Crestor) (156) and fenofibrate (Tricor) (154) has been gaining popularity among vascular physicians and cardiologists. Rosuvastatin can keep LDL very low and can also increase the plasma levels of HDL (97,156). Fenofibrate (94) m the morning can bring a remarkable reduction of the serum triglycerides. Rosuvastatin and fenofibrate is a safe combination therapy with regards to liver toxicity and rhabdomyolysis (154,156). 

Fenofibrate + a statin Raised triglycerides (TG), decreased HDL-C levels and a predominance of small LDL are characteristics of the metabolic syndrome. In patients with mixed hyperlipidemia and metabolic syndrome, high-dose rosuvastatin (40 mg/d, n = 30) was more effective in decreasing LDL-C and non-HDL-C levels... 

Agouridis AP, Kostapanos MS, Tsimihodimos V, Kostara C, MikhaiUdis DP, Bairaktari ET, Tselepis AD. Effect of rosuvastatin monotherapy or in combination with fenofibrate or omega-3 fatty acids on hpoprotein subfraction profile in patients with mixed dyshpidaemia and metabolic syndrome. Int J Chn Pract 2012 66 843-53. 

Kei A, Liberopoulos EN, Mikhaihdis DP. Comparison of switch to the highest dose of rosuvastatin vs. add-on nicotinic acid vs. add-on fenofibrate for mixed dyshpidaemia. Int J Chn Pract 2013 67 412-9. 

Adefovir, amlodipine, busulfan, cefaclor, cefdinir, cefixime, citalopram, cyclosporine, fenofibric acid, hydrocodone, hydromorphone, lonafarnib, nalmefene, rosuvastatin voriconazole... 

Trivedi, R.K., KaUem, R.R., Mullangi, R. and Srinivas, N.R., Simultaneous determination of rosuvastatin and fenofibric acid in hnman plasma by LC-MS/MS with electrospray ionization assay development, validation and application to a clinical study. J. Pharm. Biomed. Anal., 39(3-4), 661-669 (2005). 

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