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Nizoral and Vytorin

Determining the interaction of Nizoral and Vytorin and the possibility of their joint administration.

Check result:
Nizoral <> Vytorin
Relevance: 07.12.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Using simvastatin together with ketoconazole is not recommended. Combining these medications may significantly increase the blood levels of simvastatin. This can increase the risk of side effects such as liver damage and a rare but serious condition called rhabdomyolysis that involves the breakdown of skeletal muscle tissue. In some cases, rhabdomyolysis can cause kidney damage and even death. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. Let your doctor know immediately if you have unexplained muscle pain, tenderness, or weakness during treatment with simvastatin or similar medications, especially if these symptoms are accompanied by fever or dark colored urine. You should also seek immediate medical attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of lovastatin and simvastatin as well as their pharmacologically active metabolites, all of which are primarily metabolized by the isoenzyme. The interaction has been reported with potent CYP450 3A4 inhibitors such as azole antifungal agents, macrolide antibiotics, HIV protease inhibitors, and nefazodone. Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma may be associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Due to the potential for severe interaction, concomitant use of lovastatin or simvastatin with potent CYP450 3A4 inhibitors is considered contraindicated. Red yeast rice, which contains lovastatin, should also be avoided during treatment with a potent CYP450 3A4 inhibitor. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are probably safer alternatives, since they are not metabolized by CYP450 3A4. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References
  • Neuvonen PJ, Kantola T, Kivisto KT "Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole." Clin Pharmacol Ther 63 (1998): 332-41
  • Horn M "Coadministration of itraconazole with hypolipidemic agents may induce rhabdomyolysis in healthy individuals." Arch Dermatol 132 (1996): 1254
  • Akram K, Rao S, Parker M "A lesson for everyone in drug-drug interactions." Int J Cardiol 118 (2007): e19-20
  • Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
  • Lomaestro BM, Piatek MA "Update on drug interactions with azole antifungal agents." Ann Pharmacother 32 (1998): 915-28
  • Gilad R, Lampl Y "Rhabdomyolysis induced by simvastatin and ketoconazole treatment." Clin Neuropharmacol 22 (1999): 295-7
  • Kivisto KT, Kantola T, Neuvonen PJ "Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin." Br J Clin Pharmacol 46 (1998): 49-53
  • Neuvonen PJ, Jalava KM "Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 60 (1996): 54-61
  • Itakura H, Vaughn D, Haller DG, O'Dwyer PJ "Rhabdomyolysis from cytochrome p-450 interaction of ketoconazole and simvastatin in prostate cancer." J Urol 169 (2003): 613
  • Kantola T, Kivisto KT, Neuvonen PJ "Effect of itraconazole on the pharmacokinetics of atorvastatin." Clin Pharmacol Ther 64 (1998): 58-65
  • Lees RS, Lees AM "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med 333 (1995): 664-5
  • Stein CA, Goel S, Ghavamian R "Hepatitis and rhabdomyolysis in a patient with hormone refractory prostate cancer on ketoconazole and concurrent lovastatin therapy." Invest New Drugs 25 (2007): 277-8
  • Kantola T, Kivisto KT, Neuvonen PJ "Effect of itraconazole on cerivastatin pharmacokinetics." Eur J Clin Pharmacol 54 (1999): 851-5
  • Watkins JL, Atkinson BJ, Pagliaro LC "Rhabdomyolysis in a prostate cancer patient taking ketoconazole and simvastatin: case report and review of the literature." Ann Pharmacother 45 (2011): e9
Nizoral

Generic Name: ketoconazole

Brand name: Nizoral

Synonyms: n.a.

Vytorin

Generic Name: ezetimibe / simvastatin

Brand name: Vytorin

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

Interaction with food and lifestyle
Disease interaction