Abstract
BackgroundDystonia is a known neurological complication of certain medications; however, the mechanism behind such effects is often undetermined. Similarly, the clinical pharmacogenomic effects associated with various alleles of the cytochrome P450 family of proteins, and their role in acute dystonic reactions, are also presently unknown.Case presentationWe describe a woman presenting with acute dystonic reactions to ondansetron, prochlorperazine, and metoclopramide followed by persistent focal dystonia. A similar family history was reported in her siblings and her father to prochlorperazine, drugs all metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. Pharmacogenomic testing indicated the patient was heterozygous for the intermediate metabolizer *41 allele (CYP2D6 2988G>A, NM_000106.6:c.985+39G>A, rs28371725). Her father was homozygous for this CYP2D6 *41 allele, and consequently, her siblings were obligate carriers.ConclusionsThe metabolism of ondansetron, metoclopramide, or prochlorperazine in patients with the *41 CYP2D6 allele has not been studied. In this family, clinical evidence implicates the *41 CYP2D6 allele as causing extrapyramidal adverse pharmacologic reactions. Patients with a family history of medication-induced dystonia involving these medications should be considered for pharmacogenomic testing, and patients carrying the *41 CYP2D6 allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects.
Highlights
ConclusionsThe metabolism of ondansetron, metoclopramide, or prochlorperazine in patients with the *41 cytochrome P450 2D6 (CYP2D6) allele has not been studied
Dystonia is a known neurological complication of certain medications; the mechanism behind such effects is often undetermined
Patients with a family history of medication-induced dystonia involving these medications should be considered for pharmacogenomic testing, and patients carrying the *41 cytochrome P450 2D6 (CYP2D6) allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects
Summary
There is limited information on the relationship between the *41 allele and dystonia. There are presently no studies assessing the *41 intermediate metabolizer allele in patients taking ondansetron, metoclopramide, or prochlorperazine; patients homozygous for inactive loss-of-function alleles (*4 or *5) in CYP2D6 have been reported with acute dystonic reactions to metoclopramide [6, [7]. In this family, the available clinical evidence points to the *41 allele being the cause of their extrapyramidal adverse pharmacologic reactions despite showing reduced activity rather than being loss-of-function. We recommend that patients with a family history of medication-induced dystonia involving ondansetron, metoclopramide, or prochlorperazine be considered for pharmacogenomic testing, and that patients carrying the *41 CYP2D6 allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects
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