Interaction of Fluconazole and Cyclosporine

Sugar, Alan M.; Saunders, Charles; Idelson, Beldon A.; Bernard, David B.

doi:10.7326/0003-4819-110-10-844_1

Cited by 63 publications

(20 citation statements)

References 2 publications

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“…Clinical interaction data are somewhat equivocal although the balance of evidence suggests that both itraconazole (Kwan et al, 1987;Trenk et al, 1987) and fluconazole, particularly at higher doses of 200 mg day-', (Graves et al, 1990;Lazar & Wilner, 1990;Sugar et al, 1989) will cause an elevation of blood CsA concentrations.…”

Section: Discussionmentioning

confidence: 99%

Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes.

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Tjia

1991

Brit J Clinical Pharma

143

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Section: Discussionmentioning

confidence: 99%

Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes.

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Tjia

1991

Brit J Clinical Pharma

143

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“…Several case reports in the literature document a drug interaction between fluconazole and the calcineurin inhibitors, 10,[34][35][36][37][38][39][40][41] although these are retrospective and uncontrolled observations. A controlled PK study of the interaction between intravenous cyclosporine/tacrolimus and intravenous fluconazole 400 mg daily in HSCT recipients demonstrated no statistically or clinically significant differences in steady-state concentration (C ss ) or clearance of tacrolimus, and a statistically but not clinically significant difference in the clearance of cyclosporine A.…”

Section: Fluconazolementioning

confidence: 99%

“…This suggests that the drug interaction is dosedependent, and that at doses of fluconazole of greater than 200 mg per day the interaction is much more likely to occur, requiring reductions in calcineurin inhibitor doses. 34,36,40 Fluconazole doses o200 mg daily typically do not require a dose adjustment of the calcineurin inhibitor. Other investigators have made similar observations.…”

Section: Fluconazolementioning

confidence: 99%

“…Other investigators have made similar observations. 34,36,38,42 The other drugs with which fluconazole has been reported to interact include rifampin, phenytoin, and warfarin. Rifampin, a potent CYP3A4, CYP2C9, and CYP2C19 isoenzyme inducer, has been shown to significantly lower the AUC of fluconazole, increase clearance, and shorten the half-life of fluconazole when concomitantly prescribed.…”

Section: Fluconazolementioning

confidence: 99%

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Drug interactions in the hematopoietic stem cell transplant (HSCT) recipient: what every transplanter needs to know

Leather

2003

Bone Marrow Transplant

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Summary:Pharmacokinetic drug interactions among hematopoietic stem cell transplant recipients can result in either increases in serum concentrations of medications, which may lead to enhanced toxicity; or reduced serum concentrations, which can lead to treatment failure and the emergence of post transplant complications. The use of drugs that have a narrow therapeutic index, such as cyclosporine/tacrolimus (calcineurin inhibitors), increases the significance of these interactions when they occur. This report will review the clinical data evaluating the drug interactions of relevance to HSCT clinical practice, focusing on the pharmacokinetic interactions, and provides recommendations for managing these interactions to avoid both toxicity and treatment failure. Keywords: drug interactions; cytochrome P450; cyclosporine; tacrolimus; pharmacokinetic; CYP3A4; azoles A drug interaction is best defined as 'the possibility that one drug may alter the intensity of pharmacological effects of another drug that is given concurrently'. This results in either enhanced activity of the affected drug, which may lead to toxicity, or reduced activity of the affected drug, leading to therapeutic failure. It is also possible that there may be the appearance of a new effect that is not seen with either drug alone, for example, caspofungin and cyclosporine coadministration leading to elevated liver function tests. Drug interactions can be categorized as being either pharmacokinetic (PK) or pharmacodynamic in nature, and the remainder of this review will focus on PK interactions. Pharmacokinetic drug interactions -what are they?Pharmacokinetic drug interactions influence the disposition of the drug in the body. When drugs are ingested, they undergo several processes to produce an end effect, including absorption, distribution, metabolism, and excretion. Interactions between two or more drugs may affect any of these phases, including the modulation of hepatic drug biotransformation, renal clearance, altered distribution, or changes in plasma protein binding. The most clinically relevant mechanisms of PK drug interactions relate to metabolism and elimination of drugs from the body, and involve the cytochrome P450 (CYP) enzymes and the transporter P-glycoprotein at the hepatic and intestinal levels, and glomerular filtration and tubular secretion at the renal level. Cytochrome microsomal enzyme systemThe CYP microsomal enzyme system is a family of hemoproteins that is responsible for the oxidative biotransformation of endogenous substrates and xenobiotics. CYPs are expressed in several tissues, with the main drug metabolizing CYPs concentrated in the liver, with lower expression in the lungs, kidneys, intestines, and brain.1 Of the several different CYP isoforms identified, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 have the greatest involvement in drug metabolism. An extensive list of drugs metabolized by the various isoenzymes is outlined in Table 1. 2 The majority of oxidatively biotransformed drugs are metabolized, at least in part, ...

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“…Studies have shown that its inhibition of CYP3A4 has resulted in elevated plasma concentrations of several immunosuppressants. This interaction between fluconazole and cyclosporine usually occurs at fluconazole doses of 200 mg per day or greater, but some reports show the interaction to be prevalent at doses of 100 mg per day [5,6]. Cyclosporine concentrations have been shown to increase threefold to fourfold after 1 week of fluconazole therapy; they peak on day 4 [6][7][8].…”

Section: Fluconazolementioning

confidence: 99%

Drug Interactions Involving Antifungal Drugs: Time Course and Clinical Significance

Bartell

Phatak

Horn

et al. 2010

Curr Fungal Infect Rep

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The antifungal armamentarium has expanded greatly over the past two decades. This expansion, along with the pharmacologically complex therapeutic regimens used in treating many patients with systemic fungal disease, enhances the risk of clinically significant drug-drug interactions. This review examines the drug-drug interaction potential of antifungal agents by pharmacologic class and attempts to provide perspective on the time course and clinical significance of these events.

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Interaction of Fluconazole and Cyclosporine

Cited by 63 publications

References 2 publications

Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes.

Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes.

Drug interactions in the hematopoietic stem cell transplant (HSCT) recipient: what every transplanter needs to know

Drug Interactions Involving Antifungal Drugs: Time Course and Clinical Significance

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