title: CYP2D6 *6/*6 genotype and drug interactions as cause of haloperidol-induced extrapyramidal symptoms.
abstract: A 66-year-old male Caucasian, received 1 mg of haloperidol orally and rapidly developed severe iatrogenic extrapyramidal symptoms. Treatment was immediately discontinued, and the side effects resolved. Haloperidol is mainly metabolized by Phase I CYP2D6 and to the lesser extent by CYP3A4 and by Phase II UGT2B7 enzymes. Genotyping was performed revealing CYP2D6*6/*6, CYP3A4*1/*1, and UGT2B7 -161 C/T genotypes, implicating poor, extensive and intermediate metabolism, respectively. Of the CYPs, haloperidol is metabolized by CYP2D6 and CYP3A4 primarily. It was the introduction of ciprofloxacin which was a trigger for the development of adverse drug reaction due to inhibition of CYP3A4, which was in presented patient main metabolic pathway for haloperidol since he was CYP2D6 poor metabolizer. Presented case report highlights the importance of genotyping. Pharmacogenetics testing should be considered when drug toxicity is suspected, polymorphic metabolic pathways used and drugs concomitantly applied.
authors.affiliation: University of Zagreb School of Medicine, Zagreb, Croatia.|Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Iveta
authors.initials: I
authors.lastname: Šimić
authors.affiliation: Clinical Unit of Clinical Pharmacology & Toxicology, Department of Medicine, University Hospital Centre Sisters of Charity, Zagreb, Croatia.
authors.forename: Ines
authors.initials: I
authors.lastname: Potočnjak
authors.affiliation: Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Iva
authors.initials: I
authors.lastname: Kraljičković
authors.affiliation: Unit for Clinical Pharmacology, University Hospital Centre Rijeka, Rijeka, Croatia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stanić Benić
authors.affiliation: Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Čegec
authors.affiliation: Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Danica
authors.initials: D
authors.lastname: Juričić Nahal
authors.affiliation: University of Zagreb School of Medicine, Zagreb, Croatia.|Department of Laboratory Diagnostics, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Lana
authors.initials: L
authors.lastname: Ganoci
authors.affiliation: University of Zagreb School of Medicine, Zagreb, Croatia.|Department of Laboratory Diagnostics, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Nada
authors.initials: N
authors.lastname: Božina
mesh_terms: D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004347:Drug Interactions; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006220:Haloperidol / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D006220:Haloperidol
keywords: adverse drug reactions; ciprofloxacin; drug interactions; haloperidol; pharmacogenetics