The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone

Varis, Tiina; Kivistö, Kari T.; Neuvonen, Pertti J.

doi:10.1007/s002280050720

Cited by 68 publications

(36 citation statements)

References 12 publications

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“…This can be explained by the fact that citalopram is a weak inhibitor of the cytochrome 450 CYP3A4, the enzyme partly responsible for metabolising prednisolone (and dexamethasone) (Bazire 2003). For example, treatment for 4 days with a well-known inhibitor of CYP3A4, itraconazole, also leads to an increase in prednisolone concentrations, although to a much larger extent (Varis et al 2000). Other antidepressants, including SSRIs and tricyclic, also inhibit CFYP3A4, and therefore could increase prednisolone or dexamethasone concentrations (Bazire 2003).…”

Section: Discussionmentioning

confidence: 96%

Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers

et al. 2004

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Section: Discussionmentioning

confidence: 96%

Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers

et al. 2004

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“…The index patient was on treatment with a combination of oral methylprednisolone and itraconazole. Itraconazole being a CYP3A4 enzyme inhibitor decreases the metabolism of steroids, thereby increasing their plasma concentration and half-life [22,23]. This leads to adrenal suppression and increases the propensity for other steroid-related side effects like secondary infections [24].…”

Section: Discussionmentioning

confidence: 99%

Acute Invasive Pulmonary Aspergillosis Complicating Allergic Bronchopulmonary Aspergillosis: Case Report and Systematic Review

Maturu

Agarwal

2015

Mycopathologia

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Aspergillus fumigatus can cause a variety of pulmonary syndromes including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis and invasive pulmonary aspergillosis (IPA). Occurrence of IPA and ABPA in the same patient is rare as the risk factors for ABPA and IPA are different. We describe a 45-year-old male with ABPA treated with oral methylprednisolone and itraconazole, who developed acute respiratory failure secondary to IPA, a month later. The patient subsequently improved after systemic antifungal therapy. Presumably, itraconazole by inhibiting CYP3A4 enzyme caused an increase in plasma methylprednisolone levels. This probably led to a profound immunosuppressed state, which predisposed to the development of IPA. We performed a systematic review and identified nine cases of IPA following ABPA. The disease course is fulminant, and only three of the nine patients survived. Physicians treating ABPA patients should be aware of this potentially fatal overlap. Clinical suspicion and early diagnosis are crucial to improve the patient outcomes.

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“…May decrease posaconazole bioavailability 43 Prednisolone May increase steroid levels; monitor 53 Increased prednisolone levels (13-30%), but clinical impact not likely to be significant 51,57 Increased steroid levels (11-34%); monitor 42 Not documented…”

Section: Not Documentedmentioning

confidence: 99%

Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

Worth

Blyth

Booth

et al. 2008

Internal Medicine Journal

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Antifungal prophylaxis, empirical therapy and treatment of established fungal infections in the haematology population may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes. These risks may be minimised by clinical assessment, laboratory monitoring of biochemical or haematological indices, avoidance of particular drug combinations and dose modification in certain circumstances. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. For certain agents, therapeutic drug monitoring (TDM) is warranted where non-compliance, non-linear pharmacokinetics, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Pharmacokinetics and pharmacodynamics of clinical relevance to the haematology population are discussed for the azole, polyene and echinocandin classes of antifungal agents. The evidence supporting an association between TDM and enhanced treatment outcomes is presented for individual antifungal drugs, and recommendations for clinical practice are provided. Further randomised study of newer antifungal agents, such as posaconazole, is required to explore the potential for improved clinical outcomes in association with TDM.Understanding a drug's pharmacokinetics and its pharmacodynamic effects affords the clinician the capacity to optimize drug exposure while minimizing or avoiding drug interactions and toxicities. Therapeutic drug monitoring (TDM) may also be employed during the treatment period to ensure that the selected drug dosage falls within the therapeutic window for an individual patient.These clinical caveats are particularly relevant to the haematology population where the frequent requirement for polypharmacy and the complexity of comorbidities can significantly influence the success of antifungal therapy. This section of the guidelines describes the potential drugdrug interactions and toxicities related to antifungal use and how they may be avoided. It also considers the latest

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The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone

Cited by 68 publications

References 12 publications

Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers

Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers

Acute Invasive Pulmonary Aspergillosis Complicating Allergic Bronchopulmonary Aspergillosis: Case Report and Systematic Review

Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

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