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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

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Update on drug interactions with azole antifungal agents

and .

Review published: .

Authors' objectives

To review and update the incidence, mechanism, and clinical relevance of drug interactions with azole antifungal agents.


MEDLINE was searched from January 1990 to May 1997 using the name of each antifungal and the term 'interaction' as MeSH terms. Abstracts were identified by literature citation and by review of Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to 1997.

Study selection

Study designs of evaluations included in the review

All study designs were eligible for inclusion in the review, however, randomised, controlled, double-blind studies were emphasised.

Specific interventions included in the review

The azole antifungal agents itraconazole, ketoconazole and fluconazole were examined for their interactions with: non sedating antihistamines; cisparide; cyclosporine; tacrolimus; digoxin; HMG-CoA reductase inhibitors; phenytoin; rifampin and isoniazid; warfarin; calcium-channel blockers; benzodiazepines; antiretrovirals and protease inhibitors; rifabutin; quinidine; corticosteroids; oral antidiabetic agents; antacids and sucralfate; and other agents. The majority of the data presented relate to cyclosporine, benzodiazepines and steroids.

Participants included in the review

Patients or healthy volunteers taking both azole antifungal agents and a concomitant drug.

Outcomes assessed in the review

The magnitude of the drug interaction was assessed in terms of the magnitude of the pharmacokinetic changes or a reduction in the dose of the concomitant medication.

How were decisions on the relevance of primary studies made?

The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.

Assessment of study quality

The authors do not state that they assessed validity. Data were apparently evaluated with respect to study design, however no further information was given.

Data extraction

The authors do not state how the data were extracted for the review, or how many of the authors performed the data extraction.

Methods of synthesis

How were the studies combined?

The studies were combined in a narrative review.

How were differences between studies investigated?

The authors do not state how differences between the studies were investigated.

Results of the review

The review quoted a total of 138 references. The number of studies ranged from 1 to 13 for each of the concomitant medications.

Azole antifungal indications appear to have some interaction with the majority of the drugs reviewed, although the clinical consequences of such interactions were not always clear. In some cases, such as anti-histamines or cisapride azoles antifungal agents are contraindicated. In others, including cyclosporine, digoxin, and phenytoin, drug doses should be reduced when azole antifungal agents are being used concomitantly. The interaction of corticosteroids with ketoconazole appears to be minimal, but here was no evidence for any interaction with itraconazole or fluconazole.

Authors' conclusions

Drug interactions with azoles are diverse and likely to be encountered by pharamcists practising in most areas of health care.

CRD commentary

This systematic review is of relatively poor quality. The aim of the review was clear and the literature search was documented, however it was limited to only one electronic database, supplemented with a search of conference proceedings and some retrieval bias is likely. The inclusion and exclusion criteria for the review were not made explicit, and no validity assessment of the included studies was reported. Study details were provided only for three of the concomitant medications considered. Few details were presented for the other medications, and it was difficult to identify the design of the included studies. A narrative review was undertaken, which is appropriate given the differences in the studies included, however the implications regarding the use of azoles with each drug were not clear, in particular the clinical implications of any identified drug interactions. The conclusions of the authors are justified, however more explicit recommendations regarding the concomitant use of azoles with each of the drugs reviewed would have been helpful.

Implications of the review for practice and research

The authors did not state any implications for further research and practice.

Bibliographic details

Lomaestro B M, Piatek M A. Update on drug interactions with azole antifungal agents. Annals of Pharmacotherapy 1998; 32(9): 915-928. [PubMed: 9762380]

Indexing Status

Subject indexing assigned by NLM


Animals; Antifungal Agents /adverse effects /pharmacokinetics /therapeutic use; Azoles /adverse effects /pharmacokinetics /therapeutic use; Drug Interactions; Humans; MEDLINE; Randomized Controlled Trials as Topic



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

Copyright © 2014 University of York.
Bookshelf ID: NBK67258


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