A published case from the British Medical Journal (January 2017) of a woman who reported quite extreme tiredness and shortness of breath while taking itraconazole. the lady was checked for common causes of tiredness eg anaemia, blood sugar and a few other possible explanations which were ruled out, but soon it became clear that she had very low adrenal gland activity.
This was not a straightforward diagnosis as the patient had been taking itraconazole for two years prior to experiencing this problem, however the conclusion reached was that the combination of taking oral itraconazole along with an inhaled fluticasone caused suppression of the adrenal glands (though not in the same way that causes Cushing syndrome). This drug regimen is relatively common amongst patients being treated for allergic bronchopulmonary aspergillosis (ABPA).
On checking another group of patients who take both of these drugs it was found that 10 out of 12 had some adrenal suppression, in 2 of which it was quite severe. We can conclude that this is not a rare condition!
Any patient experiencing excessive tiredness while taking itraconazole might want to discuss this possibility with their doctors - low adrenal function is easily testable via a simple blood test.
Itraconazole is far from the only drug that can interact in this way as many drugs will inhibit the cytpochrome p450 enzyme system which has been implicated in causing the problem here. Strong inhibitiors include other antifungal medication (see the Fungal Infection Trust interaction database for detailed information) and this paper also lists several more strong inhibitors, including antibiotics. Many more drugs are moderate inhibitors of CYP450 and even some foods such as grape juice can also inhibit.
BMJ make the point that this information makes it all the more important that patients tell their doctors all of their drug history in order to help avoid these interactions.