Investigational New Drugs

, Volume 25, Issue 3, pp 277–278 | Cite as

Hepatitis and rhabdomyolysis in a patient with hormone refractory prostate cancer on ketoconazole and concurrent lovastatin therapy

  • C. A. SteinEmail author
  • Sanjay Goel
  • Reza Ghavamian
Short Report

Itakura et al. [1] have recently reported a case of a 73-year old man with hormone refractory prostate cancer who experienced rhabdomyolysis after treatment with the azole drug ketoconazole plus hydrocortisone while concurrently receiving simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Ketoconazole is a potent inhibitor of the enzyme cytochrome P450 [CYP] 3A4; several statins, including simvastatin and lovastatin, interact with this hepatic microsomal enzyme, which is responsible in significant part for statin clearance [2]. Since the number of men treated with the combination of ketoconazole and hydrocortisone for prostate malignancy is increasing, Itakura et al. [1] predicted that rhabdomyolysis will become more prevalent. However, it is not clear if the statin/ketoconazole drug interaction leading to rhabdomyolysis in men with prostate cancer is a general property of the statins as a drug class, or is an event relatively restricted to simvastatin [3]. For...


Ketoconazole Hepatitis Rhabdomyolysis Lovastatin Prostatic neoplasms 


  1. 1.
    Itakura H, Vaughn D, Haller D, O’Dwyer P (2003) Rhabdoymolysis from cytochrome P-450 interaction of ketoconazole and simvastatin in prostate cancer. J Urol 169:613PubMedCrossRefGoogle Scholar
  2. 2.
    Williams D, Feely J (2002) Pharmacokinetic-pharmacosdynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 41:343PubMedCrossRefGoogle Scholar
  3. 3.
    Gilad R, Laml Y (1999) Rhabdomyolysis induced by simvastatin and ketoconazole treatment. Clin Neuropharmacol 22:295PubMedGoogle Scholar
  4. 4.
    Neuvonen P, Kantola T, Kivisto K (1998) Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 63:332PubMedCrossRefGoogle Scholar
  5. 5.
    Bays H, Dujovne C (1998) Drug interactions of lipid-altering drugs. Drug Saf 5:355CrossRefGoogle Scholar
  6. 6.
    Chung E, Nafziger A, Kazierad D, Bertino J Jr (2006) Comparison of midazolam and simvastatin as cytochrome P450 3A inhibitors. Clin Pharm Ther 79:350CrossRefGoogle Scholar
  7. 7.
    East C, Alivizatios P, Grundy S et al (1988) Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation. N Engl J Med 318:47PubMedCrossRefGoogle Scholar
  8. 8.
    Gullestad L, Nordal K, Berg K et al (1999) Interaction between lovastatin and cyclosporine A after heart and kidney transplantation. Transplant Proc 31:2163PubMedCrossRefGoogle Scholar
  9. 9.
    Tobert J (1988) Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation. N Engl J Med 318:48CrossRefGoogle Scholar
  10. 10.
    Tolman K (2000) Defining patient risks from expanded preventive therapies. Amer J Cardiol 85:15EPubMedCrossRefGoogle Scholar
  11. 11.
    Grimbert S, Pessayre D, Degott C, Benhamou JP (1994) Acute hepatitis induced by HMG-CoA reductase inhibitor, lovastatin. Dig Dis Sci 39:2032–2033PubMedCrossRefGoogle Scholar
  12. 12.
    Mantell G, Burke MT, Staggers J (1990) Extended clinical safety profile of lovastatin. Am J Cardiol 66:11B–15BPubMedCrossRefGoogle Scholar
  13. 13. Downloaded Oct 30, 2006Google Scholar
  14. 14.
    Velayudham L, Farrell G (2003) Drug-induced cholestasis. Expert Opin Drug Saf 2:287PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Albert Einstein College of Medicine and Montefiore Cancer CenterBronxUSA
  2. 2.Department of Oncology, Montefiore Medical CenterBronxUSA

Personalised recommendations