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Ketoconazole Disease Interactions

There are 4 disease interactions with ketoconazole:

Major

Ketoconazole (Includes Ketoconazole) ↔ Hepatotoxicity

Severe Potential Hazard, High plausibility

Applies to: Liver Disease

Serious hepatotoxicity including cases with a fatal outcome or requiring liver transplant have been reported. Some patients had no obvious risk factors for liver disease. Liver function tests should be performed prior to initiation of therapy and regularly during treatment in patients receiving prolonged therapy with ketoconazole, particularly those with a current or past history of liver disease. Therapy should be withdrawn if persistent elevations or worsening of liver enzyme levels occur, or if the abnormalities are accompanied by symptoms of possible liver injury. Since ketoconazole is primarily metabolized by the liver, empirically reducing the dosage may also be appropriate in patients with existing liver disease. The use of oral ketoconazole tablets is contraindicated in patients with acute or chronic liver disease.

References

  1. "Product Information. Nizoral (ketoconazole)." Janssen Pharmaceutica, Titusville, NJ.
  2. Stricker BH, Blok AP, Bronkhorst FB, et al "Ketoconazole-associated hepatic injury: a clinicopathological study of 55 cases." J Hepatol 3 (1986): 399-406
  3. Bercoff E, Bernuau J, Degott C, et al "Ketoconazole-induced fulminant hepatitis." Gut 26 (1985): 636-8
  4. van Parys G, Evenepoel C, van Damme B, Desmet VJ "Ketoconazole-induced hepatitis: a case with a definite cause-effect relationship." Liver 7 (1987): 27-30
  5. Knight TE, Shikuma CY, Knight J "Ketoconazole-induced fulminant hepatitis necessitating liver transplantation." J Am Acad Dermatol 25 (1991): 398-400
  6. Lake-Bakaar G, Scheuer PJ, Sherlock S "Hepatic reactions associated with ketoconazole in the United Kingdom." Br Med J (Clin Res Ed) 294 (1987): 419-22
  7. Lewis JH, Zimmerman HJ, Benson GD, Ishak KG "Hepatic injury associated with ketoconazole therapy: analysis of 33 cases." Gastroenterology 86 (1984): 503-13
  8. Gradon JD, Sepkowitz DV "Massive hepatic enlargement with fatty change associated with ketoconazole." Ann Pharmacother 24 (1990): 1175-6
  9. Duarte PA, Chow CC, Simmons F, Ruskin J "Fatal hepatitis associated with ketoconazole therapy." Arch Intern Med 144 (1984): 1069-70
  10. McCance DR, Ritchie CM, Sheridan B, Atkinson AB "Acute hypoadrenalism and hepatotoxicity after treatment with ketoconazole." Lancet Mar (1987): 573
  11. Chien RN, Yang LJ, Lin PY, Liaw YF "Hepatic injury during ketoconazole therapy in patients with onychomycosis: a controlled cohort study." Hepatology 25 (1997): 103-7
View all 11 references
Moderate

Azole Antifungals (Includes Ketoconazole) ↔ Qt Prolongation

Moderate Potential Hazard, Moderate plausibility

Applies to: Arrhythmias

Most of the azole antifungals have been associated with prolongation of the QT interval. There have been postmarketing rare reports of QT prolongation, and torsade de pointes usually involving patients with risk factors such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Moderate

Ketoconazole (Includes Ketoconazole) ↔ Achlorhydria

Moderate Potential Hazard, High plausibility

Applies to: Achlorhydria

Nizoral (brand of ketoconazole) tablets require acidity for proper dissolution and absorption. Therefore, the drug may not be effective in patients with achlorhydria. Taking the medication with an acidic beverage such as orange or cranberry juice may help, but an alternative antifungal agent should be considered.

References

  1. Daneshmend TK, Warnock DW, Ene MD, et al "Influence of food on the pharmacokinetics of ketoconazole." Antimicrob Agents Chemother 25 (1984): 1-3
  2. Mannisto PT, Mantyla R, Nykanen S, et al "Impairing effect of food on ketoconazole absorption." Antimicrob Agents Chemother 21 (1982): 730-3
  3. Lake-Bakaar G, Tom W, Lake-Bakaar D, et al "Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome (AIDS)." Ann Intern Med 109 (1988): 471-3
  4. "Product Information. Nizoral (ketoconazole)." Janssen Pharmaceutica, Titusville, NJ.
  5. Daneshmend TK "Diseases and drugs but not food decrease ketoconazole "bioavailability"." Br J Clin Pharmacol 29 (1990): 783-4
View all 5 references
Moderate

Ketoconazole (Includes Ketoconazole) ↔ Adrenal Insufficiency

Moderate Potential Hazard, Moderate plausibility

Applies to: Adrenal Insufficiency

Ketoconazole tablets decrease adrenal corticosteroid secretion at doses of 400 mg and higher. Adrenal function should be monitored in patients with adrenal insufficiency or with borderline adrenal function and in patients with prolonged periods of stress due to major surgery, intensive care, etc.

ketoconazole drug Interactions

There are 773 drug interactions with ketoconazole

ketoconazole alcohol/food Interactions

There is 1 alcohol/food interaction with ketoconazole

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No information available.

Do not stop taking any medications without consulting your healthcare provider.

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