Selected Azoles/Selected HMG-CoA Reductase Inhibitors
This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.
Severe. These medicines may interact and cause very harmful effects and are usually not taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.
How the interaction occurs:
When these two medicines are taken together, your body may not process your cholesterol medicine properly.
What might happen:
Your blood levels of your cholesterol medicine may increase and cause possible toxic effects.
What you should do about this interaction:
Let your healthcare professionals (e.g. doctor or pharmacist) know right away that you are taking these medicines together. You may need to take a different cholesterol medicine.Tell your doctor right away if you experience muscle pain, tenderness, or weakness; unexplained tiredness; or discolored urine.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.
1.Mevacor (lovastatin) US prescribing information. Merck & Co., Inc. February, 2014.
2.USFood and Drug Administration. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. available at: http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm June 8, 2011.
3.Zocor (simvastatin) US prescribing information. Merck & Co., Inc. February, 2014.
4.Vytorin (ezetimibe/simvastatin) US prescribing information. Merck/Schering-Plough Pharmaceuticals February, 2014.
5.Sporanox (itraconazole) US prescribing information. Janssen Pharmaceutica Products, L.P. April, 2012.
6.Noxafil (posaconazole) UK summary of product characteristics. Schering-Plough Ltd. February 2, 2006.
7.Noxafil (posaconazole) US prescribing information. Merck & Co. Inc March, 2014.
8.Lipitor (atorvastatin) US prescribing information. Pfizer Inc. October, 2012.
9.Baycol (cerivastatin) US prescribing information. Bayer Corporation December, 2000.
10.Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998 Jul; 64(1):58-65.
11.Jacobson TA. Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol 2004 Nov 1;94(9):1140-6.
12.Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P. Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000 Oct;68(4):391-400.
13.Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on cerivastatin pharmacokinetics. Eur J Clin Pharmacol 1999 Jan; 54(11):851-5.
14.Neuvonen PJ, Jalava KM. Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1996 Jul;60(1):54-61.
15.Kivisto KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998 Jul;46(1):49-53.
16.Neuvonen PJ, Kantola T, Kivisto KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998 Mar;63(3):332-41.
17.Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Baner K, Benet LZ, Sewing KF, Christians U. Small intestinal metabolism of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin and comparison with pravastatin. J Pharmacol Exp Ther 1999 Oct;291(1):131-9.
18.Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Benet LZ, Sewing KF, Christians U. Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos 1999 Feb;27(2):173-9.
19.Ishigam M, Uchiyama M, Kondo T, Iwabuchi H, Inoue S, Takasaki W, Ikeda T, Komai T, Ito K, Sugiyama Y. Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions. Pharm Res 2001 May;18(5):622-31.
20.Krishna G, Ma L, Prasad P, Moton A, Martinho M, O'Mara E. Effect of posaconazole on the pharmacokinetics of simvastatin and midazolam in healthy volunteers. Expert Opin Drug Metab Toxicol 2012 Jan;8(1):1-10.
21.Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med 1995 Sep 7; 333(10):664-5.
22.Horn M. Coadministration of itraconazole with hypolipidemic agents may induce rhabdomyolysis in healthy individuals. Arch Dermatol 1996 Oct; 132(10):1254.
23.Segaert MF, De Soete C, Vandewiele I, Verbanck J. Drug-interaction-induced rhabdomyolysis. Nephrol Dial Transplant 1996 Sep;11(9):1846-7.
24.Roques S, Lytrivi M, Rusu D, Devriendt J, De Bels D. Rhabdomyolysis-induced acute renal failure due to itraconazole and simvastatin association. Drug Metabol Drug Interact 2011;26(2):79-80.
25.Tiessen RG, Lagerwey HJ, Jager GJ, Sprenger HG. Drug interaction caused by communication problems. Rhabdomyolysis due to a combination of itraconazole and simvastatin. Ned Tijdschr Geneeskd 2010;154:A762.
26.Saliba WR, Elias M. Severe myopathy induced by the co-administration of simvastatin and itraconazole. Eur J Intern Med 2005 Aug;16(4):305.
27.Vlahakos DV, Manginas A, Chilidou D, Zamanika C, Alivizatos PA. Itraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treated with simvastatin and cyclosporine. Transplantation 2002 Jun 27;73(12):1962-4.
28.Maxa JL, Melton LB, Ogu CC, Sills MN, Limanni A. Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil, and itraconazole. Ann Pharmacother 2002 May;36(5):820-3.
29.Gilad R, Lampl Y. Rhabdomyolysis induced by simvastatin and ketoconazole treatment. Clin Neuropharmacol 1999 Sep-Oct;22(5):295-7.
30.Watkins JL, Atkinson BJ, Pagliaro LC. Rhabdomyolysis in a Prostate Cancer Patient Taking Ketoconazole and Simvastatin: Case Report and Review of the Literature (February). Ann Pharmacother 2011 Feb 8.
31.Itakura H, Vaughn D, Haller DG, O'Dwyer PJ. Rhabdomyolysis from cytochrome p-450 interaction of ketoconazole and simvastatin in prostate cancer. J Urol 2003 Feb;169(2):613.
32.Phansalkar S, Desai AA, Bell D, Yoshida E, Doole J, Czochanski M, Middleton B, Bates DW. High-priority drug-drug interactions for use in electronic health records. J Am Med Inform Assoc 2012 Sep-Oct; 19(5):735-43.
33.Nizoral (ketoconazole oral) US prescribing information. Janssen Pharmaceuticals February, 2014.