Abstract
Selective serotonin reuptake inhibitors can be added to clozapine therapy in order to treat remaining negative symptoms and obsessive compulsive symptoms. The present case report describes a 44‐year‐old man exhibiting extremely elevated plasma levels of clozapine after the addition of fluvoxamine, up to 4160 mcg/l. The elevated plasma levels of clozapine, which were discovered 6 months after the SSRI was added, is likely to be caused by a drug‐drug interaction. Clozapine is a substrate of CYP 1A2 and is predominantly metabolised in the liver. Of the SSRIs, fluvoxamine is one of the most potent inhibitors of the isoenzyme CYP 1A2. This case serves to emphasise the need for continuous attention to drug‐drug interactions, especially when they might be easily overlooked due to the lack of clear symptoms.
Similar content being viewed by others
References
Fitton A, Heel RC. Clozapine. A review of its pharmacological properties, and therapeutic use in schizophrenia. Drugs 1990;40:722-47.
Baker RW, Chengapa KN, Baird YW, Steingard S, Christ MA, Schooler NR. Emergence of obsessive compulsive symptoms during treatment with clozapine. J Clin Psychiatry 1992;53:439-42.
Szegedi A, Wiesner J, Hiemke C. Improved efficacy and fewer side effects under clozapine treatment after addition of fluvoxamine. J Clin Psychopharmacol 1995;154:141-143.
Weigmann H, Müller H, Dahmen N, Wetzel H, Hiemke C. Interactions of fluvoxamine with the metabolism of clozapine. Pharmacopsychiatry 1993;26:209.
Markowitz JS, Gill HS, Lavia M, Brewerton TD, DeVane CL. Fluvoxamine-clozapine dose dependent interaction. Can J Psychiatry 1996; 41:670-671.
Hiemke C, Weigman H, Härtter S, Dahmen N, Wetzel H, Müller H. Elevated levels of clozapine in serum after addition of fluvoxamine. J Clin Psychopharmacol 1994;14:279-281.
Jerling M, Lindström L, Bondesson U, Bertilsson L. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther. Drug. Monit 1994;16:368-374.
Chong SA, Tan CH, Lee HS. Worsening of psychosis with clozapine and selective serotonin reuptake inhibitor combination: two case reports. J Clin Psychopharmacol 1997;17:68-69.
Centorrino F, Baldessarini RJ, Frankenburg FR, Kando J, Volpicelli SA, Flood JG. Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors. Am J Psychiatry 1996;153:820-822.
Brøsen K. The pharmacogentics of the selective serotonin reuptake inhibitors. Clin Invest 1993;71:1002-1009.
Fuhr U. Drug interactions with grapefruit juice. Extent, probable mechanism and clinical relevance. Drug Safety 1998;18:251-272.
Rights and permissions
About this article
Cite this article
Heeringa, M., Beurskens, R., Schouten, W. et al. Elevated plasma levels of clozapine after concomitant use of fluvoxamine. Pharm World Sci 21, 243–244 (1999). https://doi.org/10.1023/A:1008748110692
Issue Date:
DOI: https://doi.org/10.1023/A:1008748110692