**4. References**


therapy with fenofibrate and statins may be useful for achieving anti-aging effects and reducing oxidative stress. However, the evaluation methods for antioxidant activity in

The serum uric acid-reducing actions of fenofibrate are regarded as one of its characteristic pleiotropic effects. The action mechanism may be mediated by a uric acid transporter, URAT1, but not by PPAR-. This may suggest that among fibrate preparations fenofibrate may be favorably administered to the patients with high serum TG and high uric acid levels,

The large-scale clinical study of fenofibrate (FIELD) showed that early administration to "primary prevention" diabetics without a history of cardiovascular events inhibited the onset of cardiovascular events. Furthermore, the DAIS, FIELD, and ACCORD-EYE studies suggested that early fenofibrate administration to all diabetics with dyslipidemia should inhibit the deterioration of diabetic complications regardless of the duration of disease or

Fenofibrate shows pleiotropic actions, especially a variety of clinical effects that may not be achieved by statins. This agent may be useful for inhibiting the deterioration of

Abate, N., Chandalia, M., Cabo-Chan, A.V. Jr., Moe, O.W. & Sakhaee, K. (2004). The

ACCORD Study Group. (2010). Effects of combination lipid therapy in type 2 diabetes mellitus. *N Engl J Med,* Vol.362, No.17, (Apr 2010), pp.1563-1574, ISSN 0028-4793 ACCORD Study Group, ACCORD Eye Study Group. (2010). Effects of medical therapies on

Asano, A., Kobayashi, J., Murase, Y., Nohara, A., Kawashiri, M.A., Inazu, A., Shimizu, M. &

study. *Lancet,* Vol.357, No.9260, (Mar 2001), pp.905-910, ISSN 0140-6736 DAIS investigators. (2003). Relationships between low-density lipoprotein particle size,

DAIS Investigators. (2005). Fenofibrate reduces progression to microalbuminuria over 3

metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. *Kidney Int,* Vo.65, No.2, (Feb 2004), pp.386-392,

retinopathy progression in type 2 diabetes. *N Engl J Med,* Vol.363, No.3, (Jul 2010),

Mabuchi, H. (2006). Effects of fenofibrate therapy on plasma ubiquinol-10 and ubiquinone-10 levels in Japanese patients with hyperlipidemia and type 2 diabetes mellitus. *Pharmacotherapy,* Vol.26, No.4, (Apr 2006), pp.447-451, ISSN 0277-0008 DAIS investigators. (2001). Effect of fenofibrate on progression of coronary-artery disease in

type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised

plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Intervention Study (DAIS). *Circulation,* Vol.107, No.13, (Apr 2003),

years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS). *Am J Kidney Dis,* Vol.45, No.3, (Mar

arteriosclerosis, and may play a role as an anti-aging panacea if properly used.

human should be strictly reviewed in the near future.

risk of events.

**4. References** 

ISSN 0085-2538

pp.233-244, ISSN 0028-4793

pp.1733-1737, ISSN 0009-7322

2005), pp.485-493, ISSN 0272-6386

as no other fibrate preparations can reduce the serum level of uric acid.


Fenofibrate: Panacea for Aging-Related Conditions? 457

Schoonjans, K., Staels, B. & Auwerx, J. (1996b). Role of the peroxisome proliferator-activated

expression. *J Lipid Res,* Vol.37, No.5, (May 1996), pp.907-925. ISSN 0022-2275 Schretlen, D.J., Inscore, A.B., Jinnah, H.A., Rao, V., Gordon, B. & Pearlson, G.D. (2007).

Souen, S. (2007). Mortality and causes of death in RA patients. *Rheumatology,* Vol.37, No.2,

Staels, B., Vu-Dac, N., Kosykh, V.A., Saladin, R., Fruchart, J.C., Dallongeville, J. & Auwerx, J.

Staels, B., Koenig, W., Habib, A., Merval, R., Lebret, M., Torra, I.P., Delerive, P., Fadel, A.,

Superko, H.R. (2000). Small, dense, low-density lipoprotein and atherosclerosis. *Curr Atheroscler Rep,* Vol.2, No.3, (May 2000), pp.226-231, ISSN 1523-3804 Tsimihodimos, V., Kostoula, A., Kakafika, A., Bairaktari, E., Tselepis, A.D., Mikhaikidis, D.P.

Turunen, M., Peters, J.M., Gonzalez, F.J., Schedin, S. & Dallner, G. (2000). Influence of

Uetake, D., Ohno, I., Ichida, K., Yamaguchi, Y., Saikawa, H., Endou, H. & Hosoya, T. (2010).

Vu-Dac, N., Schoonjans, K., Laine, B., Fruchart, J.C., Auwerx, J. & Staels, B. (1994). Negative

Vu-Dac, N., Schoonjans, K., Kosykh, V., Dallongeville, J., Fruchart, J.C., Staels, B. & Auwerx,

*Biol,* Vol.297, No.3, (Mar 2000), pp.607-614, ISSN 0022-2836

Vol.49, No.2, (Jan 2010), pp.89-94, ISSN 0918-2918

No.2, (Aug 1995), pp.741-750, ISSN 0021-9738

*Neuropsychology.* Vol.21, No.1, (Jan 2007), pp.136-140, ISSN 0894-4105 Shinomiya, F., Mima, N., Nanba, K., Tani, K., Nakano, S., Egawa, H., Sakai, T., Miyoshi, H.

(Apr 2008), pp.165-169, ISSN 1439-7595

(Feb 2007), pp.164-168, ISSN 0915-227X

ISSN 0021-9738

0028-0836

pp.27-33, ISSN 1074-2484

ISSN 0021-9258

receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene

Serum uric acid and cognitive function in community-dwelling older adults.

& Hamada, D. (2008). Life expectancies of Japanese patients with rheumatoid arthritis: a review of deaths over a 20-year period. *Mod Rheumatol,* Vo.18, No.2,

(1995). Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. *J Clin Invest,* Vol.95, No.2, (Feb 1995), pp.705-712,

Chinetti, G., Fruchart, J.C., Najib, J., Maclouf, J. & Tedgui, A. (1998). Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. *Nature,* Vol.393, No.6687, (Jun 1998), pp.790-793, ISSN

& Elisaf, M. (2004). Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values. *J Cardiovasc Pharmacol Ther,* Vol.9, No.1, (Mar 2004),

peroxisome proliferator-activated receptor alpha on ubiquinone biosynthesis. *J Mol* 

Effect of fenofibrate on uric acid metabolism and urate transporter 1. *Intern Med,*

regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. *J Biol Chem,* Vol.269, No.49, (Dec 1994), pp.31012-31018, ISSN

J. (1995). Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. *J Clin Invest,* Vol.96,


Lippi, G., Montagnana, M., Franchini, M., Favaloro, E.J. & Targher, G. (2008). The

Mabuchi, H., Higashikata, T., Kawashiri, M.,Katsuda, S., Mizuno, M., Nohara, A., Inazu, A.,

Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A. & Tschopp, J. (2006). Gout-associated uric

Muhlestein, J.B., May, H.T., Jensen, J.R., Home, B.D., Lanman, R.B., Lavasani, F., Wolfert,

Romano, A.D., Serviddio, G., de Matthaeis, A., Bellanti, F. & Vendemiale, G. (2010).

Ross, R. (1999). Atherosclerosis--an inflammatory disease. *N Engl J Med,* Vol.340, No.2, (Jan

Schlesinger, N., Dalbeth, N. & Perez-Ruiz, F. (2009). Gout-what are the treatment options? *Expert Opin Pharmacother*, Vol.10, No.8, (Jun 2009), pp.1319-1328, ISSN 1465-6566 Schmelzer, C., Kubo, H., Mori, M., Sawashita, J., Kitano, M., Hosoe, K., Boomgaarden,

Schmelzer, C., Okun, JG., Haas, D., Higuchi, K., Sawashita, J., Mori, M. & Döring, F. (2010b).

Schoonjans, K., Watanabe, M., Suzuki, H., Mahfoudi, A., Krey, G., Wahli, W., Grimaldi, P.,

Schoonjans, K., Peinado-Onsurbe, J., Lefebvre, A.M., Heyman, R.A.; Briggs, M., Deeb, S.,

gene. *EMBO J,* Vol.15, No.19, (Oct 1996), pp.5336-5348, ISSN 0261-4189

Vol.62, No.11, (Nov 2010), pp.812-818, ISSN 1521-6551

*Chim Acta,* Vol.392, No.1-2, (Jun 2008), pp.1-7, ISSN 0009-8981

*Thromb,* Vol.12, No.2, (Jun 2005), pp.111-119, ISSN 1340-3478

2006), pp.237-241, 0028-0836

401, ISSN 0735-1097

S36, ISSN 1121-8428

4133

1999), pp.115-126, ISSN 0028-4793

pp.19269-19276, ISSN 0021-9258

paradoxical relationship between serum uric acid and cardiovascular disease. *Clin* 

Koizumi, J. & Kobayashi, J. (2005). Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients. *J Atheroscler* 

acid crystals activate the NALP3 inflammasome. *Nature,* Vol.440, No.7081, (Mar

R.L., Pearson, R.R., Yannicelli, H.D. & Anderson, J.L. (2006). The reduction of inflammatory biomarkers by statin, fibrate, the combination therapy among diabeteic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. *J Am Coll Cardiol,* Vol.48, No.2, (Jul 2006), pp.396-

Oxidative stress and aging. *J Nephrol,* Vol.23, No.suppl 15, (Sep-Oct 2010), pp.S29-

I.,Döring, F. & Higuchi, K. (2010a). Supplementation with the reduced form of Coenzyme Q10 decelerates phenotypic characteristics of senescence and induces a peroxisome proliferator-activated receptor-alpha gene expression signature in SAMP1 mice. *Mol Nutr Food Res,* Vol.54, No.6, (Jun 2010), pp.805-815, ISSN 1613-

The reduced form of coenzyme Q10 mediates distinct effects on cholesterol metabolism at the transcriptional and metabolite level in SAMP1 mice. *IUBMB Life,* 

Staels, B., Yamamoto, T. & Auwerx, J. (1995). Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. *J Biol Chem*, Vol.270, No.33, (Aug 1995),

Staels, B. & Auwerx, J. (1996a). PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase


**23**

*Malaysia* 

**Predictors of the Common Adverse** 

*1Department of Clinical Pharmacy, School of Pharmaceutical Sciences,* 

Hadeer Akram AbdulRazzaq1, Noorizan Abd Aziz2, Yahaya Hassan2,

Statins are common lipid lowering agents to reduce elevation of cholesterol or as prophylaxis against other cardiac diseases. It estimated that 62.5% to 91.7% of dyslipidemic patients in United State of America are using statins1 These agents widely used among cardiovascular patients in Malaysia2. In other countries, for example in UK, it has found that most patients who use statins are older than 35 years old and more of them are males (56%)3. In Canada, about 90% of cardiac patients are using statin, while in US, at least one third of all cardiac patients are using statins4. About 60% of American patients who older than 60 years old are using statin5. Thus, high number of users contributed to increase the

The Food and Drug Administration (FDA) has determined that common statin-associated ADRs are fatigue, muscle pain, joints pain, back pain, visual disturbance and insomnia6,7. Previous studies have examined the incidence of these ADRs, and their results showed that more than half of the reported cases of muscle pain were related to statin use8,9. Clearfield et al found that fatigue, muscle pain, and bone pain were common and frequent ADRs in UK, and related to atorvastatin and rosuvastatin use10. Other studies exploring ADRs in patients using atorvastatin and lovastatin in the US found that muscle pain and fatigue were the most common statin-related ADRs11. The UK Committee on Safety of Medicines, as well as other studies, have reported that these symptoms should consider as early signs for more serious ADRs8,12-15. However, from our knowledge, no data available on the common ADRs statin-related and their predictors for Asian patients. Only a few studies (not related with Asian patients) have found out the predictors of the statin-related ADRs8,9,10,16,17. As health care professional, they should find methods to ensure patients not only receive effective medication but also feel comfortable with the therapy. Thus, the objectives of this study was to determine the common statin-related ADRs and their predictors in one of the referral

**1. Introduction** 

risk of adverse drug reactions (ADRs).

hospital in Malaysia (one of country in South East Asia).

**Drug Reactions of Statins** 

Yaman Walid Kassab1 and Omar Ismail3

*2Faculty of Pharmacy, UiTM, Puncak Alam Campus,* 

*3Department of Cardiology, Hospital Pulau Pinang, Penang,* 

*Universiti Sains, Penang,* 

*Bandar Puncak Alam, Selangor DE,* 

