Zusammenfassung
Clozapin wird über hepatische Enzyme der Zytochrom-P450- (CYP-)Familie abgebaut (Abb. 17.1), wobei die Bildung des Hauptmetaboliten Desmethylclozapin im Wesentlichen über CYP1A2 katalysiert wird (Chang et al. 1999; Eiermann et al. 1997; Olesen u. Linnet 2000; Schaber et al. 1998). Ein potenter Inhibitor von CYP1A2 ist Fluvoxamin (Baumann 1996; Buur-Rasmussen u. Brøsen 1999). Entsprechend erhöht dieser selektive Serotoninrückaufnahmehemmer (SSRI) die Bioverfügbarkeit und verlangsamt die Elimination von Clozapin (Hiemke et al. 1994; Jerling et al. 1994; Wetzel et al. 1998; Chang et al. 1999). Bei niedrigen Dosen von Clozapin und hohen von Fluvoxamin ist die Hemmung stark, umgekehrt ist sie bei hohen Dosen von Clozapin und niedrigen von Fluvoxamin gering ausgeprägt (Szegedi et al. 1999). Andere SSRI, wie Paroxetin oder Fluoxetin, wirken nur in hohen Dosen hemmend (Centorrino et al. 1996; Joos et al. 1997). Einen noch schwächeren Hemmeffekt, der ohne klinische Bedeutung zu sein scheint, besitzt Sertralin (Chong u. Remington 1998), von Citalopram ist keine pharmakokinetische Interaktion mit Clozapin zu erwarten.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
Literatur
Armstrong SC, Stephans JR (1997) Blood clozapine levels elevated by fluvoxamine: potential for side effects and lower clozapine dosage. J Clin Psychiatry 58: 499
Baumann P (1996) Pharmacokinetic-pharmacodynamic relationship of the selective serotonin re-uptake inhibitors. Clin Pharmacokinet 31: 444–469
Bender S, Eap CB (1998) Very high cytochrome P4501A2 activity and nonresponse to clozapine. Arch Gen Psychiatry 55: 1048–1050
Buur-Rasmussen B, Brosen K (1999) Cytochrome P450 and therapeutic drug monitoring with respect to clozapine. Eur Neuropsychopharmacol 9:453–459
Centorrino F, Baldessarini RJ, Frankenburg FR, Kando J, Volpicelli SA, Flood JG (1996) Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors. Am J Psychiatry 153: 820–822
Chang WH, Augustin B, Lane HY, ZumBrunnen T, Liu HC, Kazmi Y, Jann MW (1999) In-vitro and in-vivo evaluation of the drug-drug interaction between fluvoxamine and clozapine. Psychopharmacology Berl 145: 91–98
Chong SA, Tan CH, Lee HS (1997) Worsening of psychosis with clozapine and selective serotonin reuptake inhibitor combination: two case reports. J Clin Psychopharmacol 17: 68–69
Chong SA, Remington G (1998) Sertraline-clozapine interaction. Can J Psychiatry 43: 856–857
Dequardo JR, Roberts M (1996) Elevated clozapine levels after fluvoxamine initiation. Am J Psychiatry 153: 840–841
DuMortier G, Lochu A, Colen de Melo P, Ghribi O, Roche-Rabreau D, DeGrassat K, Desce JM (1996) Elevated clozapine plasma concentrations after fluvoxamine initiation. Am J Psychiatry 153: 738–739
Eiermann B, Engel G, Johansson I, Zanger UM, Bertilsson L (1997) The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 44: 439–446
Hiemke C, Weigmann H, Härtter S, Dahmen N, Wetzel H, Muller H (1994) Elevated levels of clozapine in serum after addition of fluvoxamine. J Clin Psychopharmacol 14: 279–281
Jerling M, Lindstrom L, Bondesson U, Bertilsson L (1995) Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. J Clin Psychopharmacol 15: 141–143
Joos AA, König F, Frank UG, Kaschka WP, Morike KE, Ewald R (1997) Dose-dependent pharmacokinetic interaction of clozapine and paroxetine in an extensive metabolizer. Pharmacopsychiatry 30: 266–270
Kuo FJ, Lane HY, Chang WH (1998) Extrapyramidal symptoms after addition of fluvoxamine to clozapine. J Clin Psychopharmacol 18: 483–484
Lammers CH, Deuschle M, Weigmann H, Härtter S, Hiemke C, Heese C, Heuser I (1999) Coadministration of clozapine and fluvoxamine in psychotic patients–clinical experience. Pharmacopsychiatry 32: 76–77
Markowitz JS (1997) Clozapine-fluvoxamine interaction. Clin Neuropharmacol 20: 281–282
Olesen OV, Linnet K (2000) Fluvoxamine-clozapine drug interaction: inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism. J Clin Psychopharmacol 20: 35–42
Schaber G, Stevens I, Gärtner HJ, Dietz K, Breyer-Pfaff U (1998) Pharmacokinetics of clozapine and its metabolites in psychiatric patients: plasma protein binding and renal clearance. Br J Clin Pharmacol 46: 453–459
Silver H, Kaplan A, Jahjah N (1995) Fluvoxamine augmentation for clozapine-resistant schizophrenia. Am J Psychiatry 152: 1098
Silver H, Kushnir M, Kaplan A (1996) Fluvoxamine augmentation in clozapine-resistant schizophrenia: an open pilot study. Biol Psychiatry 40: 671–674
Silver H, Nassar A (1992) Fluvoxamine improves negative symptoms in treated chronic schizophrenia: an add-on double-blind, placebo-controlled study. Biol Psychiatry 37: 698–704
Spina E, Avenoso A, Facciola G, Scordo MG, Ancione M, Madia AG, Ventimiglia A, Perucca E (2000) Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics. Psychopharmacology 148: 83–89
Stevens I, Gärtner HJ (1996) Plasma level measurement in a patient with clozapine intoxication J Clin Psychopharmacol 16: 86–87
Szegedi A, Anghelescu I, Wiesner J, Schlegel S, Weigmann H, Härtter S, Hiemke C, Wetzel H (1999) Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial. Pharmacopsychiatry 32: 148–153
Szegedi A, Wiesner J, Hiemke C (1994) Improved efficacy and fewer side effects under clozapine treatment after addition of fluvoxamine. Ther Drug Monit 16: 368–374
Wetzel H, Anghelescu I, Szegedi A, Wiesner J, Weigmann H, Härtter S, Hiemke C (1998) Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol 18: 2–9
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Hiemke, C., Hoehn, J., Weigmann, H., Oehl, W. (2001). Auftreten von Nebenwirkungen unter Clozapin-Fluvoxamin-Kombination. In: Naber, D., Müller-Spahn, F. (eds) Leponex. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59454-0_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-59454-0_17
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-41135-2
Online ISBN: 978-3-642-59454-0
eBook Packages: Springer Book Archive