Effect of Carbamazepine on Ciclosporin Blood Level

Javier Soto Alvarez, MD, C/ Calderón de la Barca No. 10, 8° dcha, E-39002 Santander (Spain) Dear Sir, Ciclosporin (CsA) is an immunosuppressive drug currently used in the prevention of the rejection of human allogenic transplants as well as in the treatment of several autoimmune diseases. CsA is metabolized in the liver by means of a P-450 cytochrome isoenzyme. Pharmacokinetic interactions resulting in both the induction and inhibition of its metabolism have been described. These interactions may induce the appearance of subtherapeutic or toxic CsA levels. Among the anticonvulsive drugs, the inductor effects of phenytoin [1] and phenobarbital [2] are well documented, while the action of carbamazepine (CBZ) is not so clear, although an inductor effect has been suggested. We have found only one case in the literature [3]. Herein, we report a kidney-transplanted patient in whom an important decrease in CsA level was noted after introducing CBZ; the CsA level returned to normal when CBZ was withdrawn. The patient was a 53-year-old male treated with immunosuppressive drugs: CsA (300 mg b.i.d.), prednisone (PRED) (20 mg b.i.d.), and azathioprine (AZA) (100 mg/ day); the clinical outcome was successful, with stable graft function during the first 8 months. He was taking chronically CsA (100 mg b.i.d.), AZA (100 mg/day), PRED (10 mg b.i.d.), insulin NPH (40 units/day), propranolol (100 mg/day) and hydralazine (50 mg/day). He was admitted to our Hospital because of acute bacterial meningitis which was treated with ampicillin intravenously (1 g q.i.d.); AZA was withdrawn, and the other drugs were not changed. Eight days later, he presented generalized tonic-clonic seizures, so CBZ was initiated (400 mg b.i.d.); the other drugs were not modified.