Doxycycline × Itraconazole

The doxycycline and itraconazole labels do not mention each other and describe no shared interaction mechanism. Itraconazole is a strong inhibitor of the CYP3A4 enzyme, but doxycycline is not cleared through it: only hepatic enzyme inducers (carbamazepine, phenytoin, barbiturates, rifampicin, chronic alcohol use) speed up its metabolism, and it is excreted through the gut and the kidney. The only common ground is the liver. Both drugs are potentially hepatotoxic: itraconazole has very rare reports of serious hepatotoxicity, including fatal acute liver failure, mostly in patients with pre-existing liver disease or taking other hepatotoxic drugs, and the doxycycline label asks for caution with potentially hepatotoxic drugs.

The documents expect no change in the concentration of either drug and describe no added adverse effects from an interaction. The liver is what to watch: loss of appetite, nausea, vomiting, fatigue, abdominal pain or dark urine are signs of hepatitis that the itraconazole label asks patients to report at once. During long doxycycline courses, liver tests, blood counts and kidney function are checked as well.

The combination is acceptable and doses stay unchanged: neither the doxycycline label nor the itraconazole label (AEMPS and FDA) names this pair. Caution concerns the liver. Potentially hepatotoxic drugs are used with caution in patients taking doxycycline (doxycycline label, 4.5), and liver function monitoring is considered in patients taking itraconazole, above all with prior liver disease or hepatotoxicity from other drugs (itraconazole label, 4.4). Patients are told to report signs of hepatitis right away: loss of appetite, nausea, vomiting, fatigue, abdominal pain or dark urine (itraconazole label, 4.4). On long doxycycline courses, blood counts and kidney and liver function are checked periodically (doxycycline label, 4.4; FDA doxycycline label, 5.11).