Solu-Cortef Drug Interactions

Hydrocortisone is metabolized by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and the cytochrome P450 (CYP) 3A4 enzyme. The CYP3A4 enzyme catalyzes 6β-hydroxylation of steroids, the essential Phase I metabolic step for both endogenous and synthetic corticosteroids. Many other compounds are also substrates of CYP3A4, some of which have been shown to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the CYP3A4 enzyme.
CYP3A4 Inhibitors: May decrease hepatic clearance and increase the plasma concentrations of hydrocortisone. In the presence of a CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin, and grapefruit juice), the dose of hydrocortisone may need to be decreased to avoid steroid toxicity.
CYP3A4 Inducers: May increase hepatic clearance and decrease the plasma concentrations of hydrocortisone. In the presence of a CYP3A4 inducer (e.g., rifampin, carbamazepine, phenobarbital, and phenytoin), the dose of hydrocortisone may need to be increased to achieve the desired response.
CYP3A4 Substrates: In the presence of another CYP3A4 substrate, the hepatic clearance of hydrocortisone may be affected, with corresponding dosage adjustments required. It is possible that adverse events associated with the use of either drug alone may be more likely to occur with co-administration.
Non-CYP3A4-Mediated Effects: Other interactions and effects that occur with hydrocortisone are described in Table 3 as follows.
Table 3 provides a list and descriptions of the most common and/or clinically important drug interactions or effects with hydrocortisone. (See Table 3.)

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