Anstieg des Clozapinspiegels bei bronchopulmonalen Infekten: Häufiger als man denkt!

Zusammenfassung

Systemische Entzündungsreaktionen können über eine Hemmung der Cytochrom-P450-Proteine die Metabolisierung verschiedener Arzneimittel beeinflussen. Hier berichten wir über 2 Patienten mit schizophrener Psychose, die während eines pulmonalen Infekts stark erhöhte Clozapinspiegel, jedoch ohne klinisch sichtbare Nebenwirkungen, aufwiesen. Nach antibiotischer Behandlung und Reduktion der Clozapindosis normalisierte sich der Clozapinspiegel nach wenigen Tagen. Bei systemischen Infekten sollte an die Möglichkeit eines erhöhten Clozapinspiegels gedacht werden.

Abstract

Systemic infections are known to alter the metabolism of various drugs via inhibition of the cytochrome P450 family. Here, we report the cases of two patients with schizophrenic psychosis and highly elevated clozapine levels during pulmonary systemic infection, however without experiencing side effects. After antibiotic treatment and temporary reduction of clozapine dosage blood levels of clozapine normalized within a few days. These cases show that clozapine levels may be highly elevated without necessarily causing side effects and that intensified pharmacovigilance should be considered by the clinician in patients with systemic infections.

Schlüsselwörter

Clozapin - Infekt - Entzündung

Keywords

clozapine - systemic infection - inflammation

• Literatur

• 1 Kuo CJ, Yang SY, Liao YT. et al. Second-generation antipsychotic medications and risk of pneumonia in schizophrenia. Schizophrenia bulletin 2013; 39: 648-657
• 2 Clark SR, Warren NS, Kim G. et al. Elevated clozapine levels associated with infection: A systematic review. Schizophrenia research 2018; 192: 50-56
• 3 de Leon J. Respiratory infections rather than antibiotics may increase clozapine levels: a critical review of the literature. The Journal of clinical psychiatry 2004; 65: 1144-1145
• 4 Morgan ET. Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clinical pharmacology and therapeutics 2009; 85: 434-438
• 5 Linnet K, Olesen OV. Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes. Drug metabolism and disposition: the biological fate of chemicals 1997; 25: 1379-1382
• 6 Bleau AM, Maurel P, Pichette V. et al. Interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and interferon-gamma released by a viral infection and an aseptic inflammation reduce CYP1A1, 1A2 and 3A6 expression in rabbit hepatocytes. European journal of pharmacology 2003; 473: 197-206
• 7 Couchman L, Morgan PE, Spencer EP. et al. Plasma clozapine, norclozapine, and the clozapine:norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 1993–2007. Therapeutic drug monitoring 2010; 32: 438-447
• 8 Stavropoulou E, Pircalabioru GG, Bezirtzoglou E. The Role of Cytochromes P450 in Infection. Frontiers in immunology 2018; 9: 89
• 9 Wong J, Delva N. Clozapine-induced seizures: recognition and treatment. Canadian journal of psychiatry Revue canadienne de psychiatrie 2007; 52: 457-463