title: Myoclonus after dextromethorphan administration in peritoneal dialysis.
abstract: OBJECTIVE
  To report a case of myoclonus that developed after administration of dextromethorphan.
  
  
  METHODS
  A 64-year-old man was diagnosed with chronic renal failure due to diabetic nephropathy. The patient started on peritoneal dialysis 6 months before he was hospitalized. Two days before hospitalization, he developed cough and sputum and he visited an outpatient clinic, where dextromethorphan was prescribed. After taking a total of 30 mg of dextromethorphan, the patient developed myoclonus, tremor, agitation, slurred speech, and diaphoresis, which continued after he stopped taking the prescribed medicine. He visited an emergency department and was hospitalized for examination and treatment of myoclonus.
  
  
  CONCLUSIONS
  As the patient's dialysis schedule was adequate, these symptoms were likely not due to uremia. The blood concentration of dextromethorphan (2.68 ng/mL) 60 hours after the 30-mg dose was higher than expected, and the blood concentration of dextrorphan, a metabolite, was lower than expected. We suspected that myoclonus was due to dextromethorphan-related symptoms induced by CYP2D6, which primarily metabolizes dextromethorphan. We analyzed the CYP2D6 gene for polymorphisms and identified CYP2D6 (*)1/(*)10. The patient had been taking metoprolol 40 mg/day for 2 years. The blood concentration of metoprolol 6 hours after administration was 13 ng/mL, which suggests that it was metabolized normally. Metoprolol has another metabolic pathway, via CYP2C19, and this may have led to its lack of accumulation. Moreover, metoprolol may have bound to active CYP2D6. Thus, affinity for CYP2D6, protein-binding rate, and lipid solubility may influence these drug interactions. Total scores for the Adverse Drug Reaction (ADR) probability scale and the Drug Interaction Probability Scale (DIPS) were 9 (highly probable) and 3 (possible), respectively.
  
  
  CONCLUSIONS
  Myoclonus and other symptoms in this patient may have been caused by a prolonged high concentration of dextromethorphan due to CYP2D6 polymorphisms and drug interactions.
authors.affiliation: Department of Pharmacy, Chubu Rosai General Hospital, Nagoya, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tanaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagamatsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nomura
authors.forename: Fumiko
authors.initials: F
authors.lastname: Nagura
authors.forename: Kayaho
authors.initials: K
authors.lastname: Maeda
authors.forename: Tatsuhito
authors.initials: T
authors.lastname: Tomino
authors.forename: Tatsuhito
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujita
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000996:Antitussive Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D003371:Cough / Q000150:complications / Q000188:drug therapy; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003915:Dextromethorphan / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D003937:Diagnosis, Differential; D004347:Drug Interactions; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D008875:Middle Aged; D009207:Myoclonus / Q000097:blood / Q000139:chemically induced*; D010530:Peritoneal Dialysis; D020230:Serotonin Syndrome / Q000175:diagnosis* / Q000235:genetics
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D000996:Antitussive Agents; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol