title: Profound metoprolol-induced bradycardia precipitated by acetaminophen-propoxyphene.
abstract: Pharmacokinetic studies demonstrate that propoxyphene is a potent inhibitor of cytochrome P450 (CYP) 2D6. Clinically significant sequelae have not been previously reported. We report a case of this inhibition manifested by life-threatening bradycardia in a patient receiving a CYP2D6 substrate, metoprolol. A 48-year-old man came to the emergency department complaining of dizziness 3 hours after ingesting metoprolol, at his usual dose, and 2 tablets of propoxyphene, newly begun postoperatively. Four hours after ingestion of both drugs, the patient was noted to have a ventricular rate of about 30 beats/min with underlying atrial fibrillation. The patient's ventricular response returned to normal within 11 hours of ingestion. We have demonstrated the clinical importance of the interaction between propoxyphene and metoprolol likely resulting from inhibition of hepatic clearance of metoprolol by propoxyphene. Underscoring the clinical relevance of CYP2D6 inhibition by an analgesic of questionable efficacy should proscribe its use.
authors.affiliation: SUNY Upstate Medical University, Syracuse, NY 13210, USA. marraffi@upstate.edu
authors.forename: Jeanna M
authors.initials: JM
authors.lastname: Marraffa
authors.forename: Li
authors.initials: L
authors.lastname: Lang
authors.forename: Gilbert
authors.initials: G
authors.lastname: Ong
authors.forename: David F
authors.initials: DF
authors.lastname: Lehmann
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects* / Q000097:blood; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects* / Q000097:blood; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000097:blood; D001919:Bradycardia / Q000503:physiopathology*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D011431:Dextropropoxyphene / Q000009:adverse effects* / Q000097:blood; D004338:Drug Combinations; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000009:adverse effects* / Q000097:blood; D008875:Middle Aged
chemical_list: D000319:Adrenergic beta-Antagonists; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004338:Drug Combinations; D000082:Acetaminophen; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol; D011431:Dextropropoxyphene