Oxcarbazepine accelerates steroid elimination in young men with epilepsy due to cytochrome P450 3A4 induction

Aims: Oxcarbazepine (OXC) induces hepatic cytochrome CYP3A4 activity, leading to lower serum concentrations of female sex-hormones and certain drugs. No studies have investigated potential alterations in corticosteroids. The observation of increased cortisol elimination in an adolescent boy with Addison's disease requiring high glucocorticoid replacement doses whilst on OXC for epilepsy (see right panel), lead us to conduct a controlled study of steroid metabolism in men on OXC.

Objective: This study aimed to compare the steroid profiles and CYP3A4 induction effects of males treated with OXC, compared to controls.

Design, subjects, methods: Six young males (14–25years) with crytogenic temporal lobe epilepsy on OXC therapy (900–1500mg/d) and six healthy male controls collected 24hour urines and had single morning blood samples taken for steroid metabolism. Main outcome were relative 24hour 6-hydroxycortisol (6-OHF) excretion, as a marker of CYP3A4 activity, and serum & 24hour urinary steroids.

Results: Accelerated CYP3A4 induction was confirmed by greater relative 24hour urinary 6-OHF/cortisol excretion in OXC patients compared to controls (see Table). Excretion of C19 and C21 steroids was similar between groups. Significantly lower estradiol and DHEAS serum levels were found in patients on OXC, but only tendencies remained after adjusting for the age difference between groups.

Conclusion: OXC induces CYP3A4 activity, leading to increased elimination of cortisol to 6-OHF, but has minimal effects on overall steroid metabolism in subjects with healthy adrenals. Caution is warranted in patients with Addison's disease on OXC where the use of longer-acting glucocorticoids should be considered. Neurologists, paediatricians and endocrinologists should be aware that epileptic patients on OXC who also take corticosteroids may require greater glucocorticoid doses to reach the desired treatment effect.