Home' Australian Pharmacist : Australian Pharmacist October 2015 Contents ADVERTORIAL
What about muscle toxicity when combining statins
Statins are associated with muscle toxicity, which is dose related, most
likely to occur in the first year of statin use and is more likely to occur in
those aged over 65 years. Risk of muscle toxicity appears to be higher in
women, in those with uncontrolled hypothyroidism or in those with renal
impairment.14 Further there is a known interaction between gemfibrozil
and statins that increases statin blood levels and therefore increases the
risk of muscle toxicity.15 However, fenofibrate does not appear to have
this significant pharmacokinetic interaction15, and there is evidence to
suggest that fenofibrate in combination with a statin has a lower rate of
rhabdomyolysis compared to gemfibrozil in combination with a statin.15
No increased risk of rhabdomyolysis was reported in ACCORD-Lipid
or FIELD.4,9 This makes fenofibrate the only fibrate recommended in
combination with statins by either the FDA or European regulators.
However, caution is still recommended as there have been reports of
myositis and rhabdomyolysis with fenofibrate monotherapy and in
combination with statins.7 Particular caution is required in patients with
predisposing factors for myopathy or rhabdomyolysis such as those with
renal impairment, the elderly or those with thyroid dysfunction.7
Other factors to consider when prescribing fenofibrate
As with all drug treatments, side effects can occur. Fenofibrate has been
associated with a photosensitive skin rash, elevated liver enzymes,
pancreatitis, thromboembolism, gallstones, and a reversible increase in
serum creatinine levels.7 Therefore regular follow-up is important, just as
it is with statin therapy.
Professor Tony Keech
Professor Anthony (Tony) Keech is a cardiologist, epidemiologist and
internationally renowned clinical trials researcher. As the Deputy Director
of the NHMRC Clinical Trials Centre (CTC), based at the University of
Sydney, Professor Keech has led some of the largest CVD trials in the
world. The opinions in this article are entirely those of Prof Keech, based
on an interview on Drivetime Radio.
This advertorial was prepared with the assistance of Belinda Butcher and
Katie Burslem from WriteSource Medical Pty Ltd, funded by BGP Products
Pty Ltd, (trading as Mylan EPD).
References: 1. Backes JM, Gibson CA, Ruisinger JF, Moriarty PM. Fibrates: what have we learned in the past 40 years?
Pharmacotherapy. 2007;27(3):412-24. 2 . Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol
lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). The Lancet.
1994;344(8934):1383-9 . 3 . Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of
coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study
Group. N Engl J Med. 1995;333(20):1301-7 . 4 . FIELD Study Investigators. Effects of long-term fenofibrate therapy
on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.
The Lancet. 2005;366(9500):1849-61. 5. Field Study Investigators. The need for a large-scale trial of fibrate therapy
in diabetes: the rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.
[ISRCTN64783481]. Cardiovasc Diabetol. 2004;3:9. 6. Food and Drug Administration. Statins: A Success Story Involving
FDA, Academia and Industry 2007. Available from: http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/
SelectionsFromFDLIUpdateSeriesonFDAHistory/ucm082054.htm. 7 . BGP Products Pty Ltd. Lipidil (fenofibrate) Product
Information. 2015. 8 . Scott R, O’Brien R, Fulcher G, Pardy C, D’Emden M, Tse D, et al. Effects of fenofibrate treatment
on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic
syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32(3):493-8 .
9. Accord Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR, 3rd, Leiter LA, et al. Effects of combination lipid
therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563-74. 10. Elam M, Lovato L, Ginsberg H. The
ACCORD-Lipid study: implications for treatment of dyslipidemia in Type 2 diabetes mellitus. Clinical Lipidology. 2011;6(1):9-
20. 11. Keech AC, Mitchell P, Summanen PA, O’Day J, Davis TME, Moffitt MS, et al. Effect of fenofibrate on the need for
laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. The Lancet. 2007;370(9600):1687-
97. 12. Accord Study Group, Accord Eye Study Group, Chew EY, Ambrosius WT, Davis MD, Danis RP, et al. Effects of
medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363(3):233-44. 13. RACGP. General
Practice Management of Type 2 Diabetes. 2014. 14 . Therapeutic Goods Administration. Medicines Safety Update: Risk
of myopathy and rhabdomyolysis with simvastatin. 2011. 15. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis
with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol. 2005;95(1):120-2. 16. Frick MH, Elo O, Haapa
K, Heinonen OP, Heinsalmi P, Helo P, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged
men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med.
1987;317(20):1237-45. 17. Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Manttari M, Heinonen OP, et al. Joint
effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in
the Helsinki Heart Study. Implications for treatment. Circulation. 1992;85(1):37-45. 18. Bezafibrate Infarction Prevention
Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery
disease. Circulation. 2000;102(1):21-7. 19. d’Emden MC, Jenkins AJ, Li L, et al. Favourable effects of fenofibrate on lipids
and cardiovascular disease in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in
diabetes (FIELD) study. Diabetologia. 2014; 57(11): 2296-303 .
Before prescribing please review PBS and Product Information available in the primary advertisement in this
publication or on request by calling 1800 225 311 or at: www.medicines.org.au
Lipidil® is a registered trademark of BGP Products Pty Ltd (trading as Mylan EPD), 299 Lane Cove Road, Macquarie Park NSW 2113. Free call: 1800 225 311.
Date prepared: August 2015. AU-LIP -2015-10 C.
• Consider fenofibrate in addition to statin therapy for those
patients with type 2 diabetes already at LDL-C target, but
who continue to have raised triglycerides and low HDL-C.
• Consider fenofibrate treatment in patients with type 2
diabetes and existing diabetic retinopathy.
TABLE 1: COMPARISON OF LIPID SUBGROUP RESULTS WITH PRIOR FIBRATE STUDIES
Helsinki Heart Study (HHS)16,17
- 34% (p<0.02)
TG >2.3 mmol/L
LDL-c/HDL-c ratio >5.0
-7 1% (p<0.005)#
- 9.4% (p=0.26) NS*
TG ≥2.3 mmol/L
- 39.5% (p=0.02)#
-1 1% (p=0.16) NS*
TG ≥2.3 mmol/L
HDL-c <1.0 mmol/L for men,
<1.3 mmol/L for women
-2 7% (p=0.005)#
-8% (p=0.32) NS*
TG ≥2.3 mmol/L
HDL-c ≤0.9 mmol/L
*NS = not significant. #Post-hoc analysis
Please note, the study design, patient population, interventions, and CV related primary endpoint definitions differ between trials.
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