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Ketoconazole (Systemic) and Mycobutin

Determining the interaction of Ketoconazole (Systemic) and Mycobutin and the possibility of their joint administration.

Check result:

Ketoconazole (Systemic) <> Mycobutin

Relevance: 10.08.2023 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:

Rifabutin may significantly reduce the blood levels of ketoconazole, which may make the medication less effective in treating your infection. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. 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:

GENERALLY AVOID: Coadministration with rifamycins may significantly decrease the plasma concentrations of both itraconazole and ketoconazole. The proposed mechanism is accelerated clearance of the azole antifungal agent due to induction of CYP450 3A4-mediated metabolism by rifamycins. Pharmacokinetic studies and case reports have demonstrated that rifampin can reduce itraconazole and ketoconazole systemic exposure by at least 80% and sometimes even to undetectable levels. Treatment failure has been reported. Rifabutin, a less potent CYP450 3A4 inducer, has been found in one study to decrease itraconazole systemic exposure by 74%. Conversely, both itraconazole and ketoconazole are potent inhibitors of CYP450 3A4 and may substantially increase the plasma levels of rifabutin and its pharmacologically active metabolite, 25-O-desacetylrifabutin. This may increase the risk of adverse effects such as leukopenia, uveitis, arthralgia, joint disorder, and skin discoloration. By contrast, itraconazole reportedly has no effect on rifampin pharmacokinetics. Ketoconazole has been found in some studies to decrease rifampin plasma levels, but interaction is apparently minimized when they are given 12 hours apart.

MANAGEMENT: The manufacturers recommend that itraconazole and ketoconazole not be used concomitantly or within 2 weeks of treatment with rifamycins, unless the benefits outweigh the risk of potentially reduced antifungal efficacy. If coadministration is required, the antifungal activity should be monitored and the azole dosage increased as necessary. With rifabutin, however, consideration should also be given to the potential for increased risk of rifabutin toxicity, particularly when the azole dosage is increased. Therapeutic drug monitoring for rifabutin is therefore advisable, and the dosage adjusted if needed. In addition, a complete blood count should be performed at least weekly and as clinically indicated to monitor for development of neutropenia.

References

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Drayton J, Dickinson G, Rinaldi MG "Coadministration of rifampin and itraconazole leads to undetectable levels of serum itraconazole." Clin Infect Dis 18 (1994): 266
Doble N, Shaw R, Rowland-Hill C, et al "Pharmacokinetic study of the interaction between rifampicin and ketoconazole." J Antimicrob Chemother 21 (1988): 633-5
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"Product Information. Sporanox (itraconazole)." Janssen Pharmaceutica, Titusville, NJ.
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Pharmaceutical Society of Australia "APPGuide online. Australian prescription products guide online. Available from: URL: http://www.appco.com.au/appguide/default.asp." ([2006]):
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Ketoconazole (Systemic)

Generic Name: ketoconazole

Brand name: Nizoral

Synonyms: Ketoconazole

What is Ketoconazole (Systemic)?

Mycobutin

Generic Name: rifabutin

Brand name: Mycobutin

Synonyms: n.a.

What is Mycobutin?

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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.

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