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Drug Interactions between ketoconazole and U-Tri-Lone

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

ketoconazole triamcinolone

Applies to: ketoconazole and U-Tri-Lone (triamcinolone)

MONITOR CLOSELY: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of triamcinolone. No pharmacokinetic data are available. However, there have been numerous published case reports of Cushing's syndrome and adrenal suppression associated with concomitant use of triamcinolone with various ritonavir-containing antiretroviral regimens and one case report with nefazodone.

MANAGEMENT: The possibility of increased corticosteroid effects should be considered when triamcinolone is used with potent CYP450 3A4 inhibitors. Some authorities advise against concomitant use unless the potential benefit outweighs the risk. If coadministration is necessary, a lower dosage of triamcinolone may be appropriate. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if triamcinolone is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma).

References

  1. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  2. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  3. Hagan JB, Erickson D, Singh RJ "Triamcinolone Acetonide Induced Secondary Adrenal Insufficiency Related to Impaired CYP3A4 Metabolism by Coadministration of Nefazodone." Pain Med (2010):
  4. Dort K, Padia S, Wispelwey B, Moore CC "Adrenal suppression due to an interaction between ritonavir and injected triamcinolone: a case report." AIDS Res Ther 6 (2009): 10
  5. Levine D, Ananthakrishnan S, Garg A "Iatrogenic Cushing syndrome after a single intramuscular corticosteroid injection and concomitant protease inhibitor therapy." J Am Acad Dermatol 65 (2011): 877-8
  6. Grierson MJ, Harrast MA "Iatrogenic Cushing Syndrome After Epidural Steroid Injections for Lumbar Radiculopathy in an HIV-Infected Patient Treated With Ritonavir: A Case Report Highlighting Drug Interactions for Spine Interventionalists." PM R 4 (2012): 234-7
  7. Albert NE, Kazi S, Santoro J, Dougherty R "Ritonavir and Epidural Triamcinolone as a Cause of Iatrogenic Cushing's Syndrome." Am J Med Sci (2012):
  8. Fessler D, Beach J, Keel J, Stead W "Iatrogenic hypercortisolism complicating triamcinolone acetonide injections in patients with HIV on ritonavir-boosted protease inhibitors." Pain Physician 15 (2012): 489-93
  9. Schwarze-Zander C, Klingmuller D, Klumper J, Strassburg CP, Rockstroh JK "Triamcinolone and ritonavir leading to drug-induced Cushing syndrome and adrenal suppression: description of a new case and review of the literature." Infection (2013):
  10. Hall JJ, Hughes CA, Foisy MM, Houston S, Shafran S "Iatrogenic Cushing syndrome after intra-articular triamcinolone in a patient receiving ritonavir boosted darunavir." Int J STD AIDS (2013):
  11. McConkey HZ, Williams H, Kulasegaram R, Graham E "Orbital floor triamcinolone causing Cushing's syndrome in a patient treated with Kaletra for HIV 1." BMJ Case Rep 2013 (2013):
  12. Sadarangani S, Berg ML, Mauck W, Rizza S "Iatrogenic Cushing Syndrome Secondary to Ritonavir-Epidural Triamcinolone Interaction: An Illustrative Case and Review." Interdiscip Perspect Infect Dis 2014 (2014): 849432
View all 12 references

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Drug and food interactions

Moderate

ketoconazole food

Applies to: ketoconazole

GENERALLY AVOID: Excessive use of alcohol or products containing alcohol together with ketoconazole or levoketoconazole may potentiate the risk of liver injury. Serious hepatotoxicity has been reported with levoketoconazole. Hepatotoxicity requiring liver transplantation has been reported with the use of oral ketoconazole, of which levoketoconazole is an enantiomer. Some patients had no obvious risk factors for liver disease. In addition, use of alcohol or products containing alcohol during ketoconazole or levoketoconazole therapy may result in a disulfiram-like reaction in some patients. Symptoms of disulfiram-like reaction include flushing, rash, peripheral edema, nausea, and headache.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of ketoconazole or levoketoconazole. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

When administered to healthy volunteers with a high-fat meal (875 calories; 62% fat), levoketoconazole systemic exposure (AUC) increased by 30% while peak plasma concentration (Cmax) did not change and the time to reach Cmax (Tmax) was delayed from 2 to 4 hours, compared to fasted conditions.

MANAGEMENT: Levoketoconazole may be administered with or without food. Excessive consumption of alcohol should generally be avoided during ketoconazole or levoketoconazole therapy. Patients should preferably avoid or limit consumption of grapefruit, grapefruit juice, or any supplement containing grapefruit extract during ketoconazole or levoketoconazole therapy. Patients receiving ketoconazole or levoketoconazole should be instructed to contact their doctor immediately if they experience swelling, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage.

References

  1. "Product Information. Ketoconazole (ketoconazole)." Mylan Pharmaceuticals Inc (2019):
  2. "Product Information. Recorlev (levoketoconazole)." Xeris Pharmaceuticals Inc (2022):
  3. Auchus R, Pivonello R, Fleseriu M, et al. "Levoketoconazole: a novel treatment for endogenous Cushing's syndrome. https://www.tandfonline.com/doi/pdf/10.1080/17446651.2021.1945440" (2022):
  4. "Product Information. Ketoconazole (ketoconazole)." Burel Pharmaceuticals Inc (2021):
View all 4 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
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 interaction information available.

Further information

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