Therapeutic monitoring of carbamazepine and its active metabolite during the 1st postnatal month: Influence of drug interactions

Abstract Objective To receive information about carbamazepine and its active metabolite 10,11-epoxide transport into mature milk and suckling infants. Methods In this cohort study, maternal serum, mature milk, and infant serum carbamazepine and epoxide levels were measured between the 6th and 29th postnatal day (carbamazepine in 1990–2017, epoxide in 1997–2017). Paired maternal serum, infant serum and milk levels were used for the assessment of ratios of this levels. The influence of combined treatment with enzyme-inducing antiepileptic drugs and valproic acid was assessed. Relationship between maternal serum, infant serum, and milk levels was also evaluated. Results Maternal carbamazepine levels were 1.4–10.4 mg/L, milk 0.5–6.7 mg/L and infant 0.5–2.6 mg/L. Maternal 10,11-epoxide levels were 0.3–5.4 mg/L, milk 0.3–3.7 mg/L and infant 0.3–0.6 mg/L. Highly significant correlations were observed exclusively between milk and maternal serum levels of both carbamazepine and 10,11-epoxide. Concomitant administration of enzyme-inducing antiepileptic drugs significantly increased the maternal apparent oral clearance of carbamazepine by approximately 130%. Carbamazepine combined with valproic acid significantly increased epoxide levels in milk and maternal serum but not in breastfed infants. Conclusions In breastfed infants, carbamazepine levels did not reach the lower limit of the therapeutic range used for the general epileptic population, and the majority of epoxide levels were less than the lower limit of quantification. Routine monitoring of carbamazepine in these infants is not compulsory. However, observation of breastfed infants is desirable. If signs of potential adverse reactions are evident, infant serum concentrations should be monitor.