title: [Extreme sinus bradycardia (30/min) with acute right heart failure under tizanidine (Sirdalud). Possible pharmacological interaction with rofecoxib (Vioxx)].
abstract: METHODS
  The case of a 59-year-old healthy woman is described, who developed an extreme sinus bradycardia (30/min) with chest pain and acute right heart failure associated with gastrointestinal symptoms and elevation of the liver enzymes while simultaneously taking tizanidine (Sirdalud), diclofenac (Voltaren), and rofecoxib (Vioxx). The symptomatology resolved promptly after stopping the medication.
  
  
  CONCLUSIONS
  The usual causes of sinusbradycardia like hypothyroidism, hypothermia, intracranial pressure elevation, typhoid fever, sick sinus syndrome, hyperreactive carotid sinus reflex, organic heart disease, electrolyte disorders, and pharmacotherapy with beta-blockers, digitalis, and antiarrhythmics have been excluded in this case. Bradycardia can occur as a side effect of tizanidine. As this substance is metabolized by cytochrome P450 1A2 and rofecoxib inhibits this enzyme, an interaction between these drugs is probable. Liver function disorders and gastrointestinal symptoms, in the present case mainly due to the acute right heart failure, have also been described as side effects under tizanidine, diclofenac as well as rofecoxib. Supposedly, the combination of tizanidine/rofecoxib used to be prescribed frequently for lumbar pain as selective cyclooxygenase-(COX-)2 inhibitors are visibly replacing the nonsteroidal antirheumatics due to their better side effect profile. An augmented risk of cardiovascular events under rofecoxib led to its withdrawal from the market at the end of September 2004.
  
  
  RESULTS
  When prescribing Sirdalud, the possible pharmacological side effects and interactions should be taken into careful account.
authors.affiliation: Abteilung für Innere Medizin, Ospedale Civico, Lugano, Schweiz. a.kick@freesurf.ch
authors.forename: Anastas
authors.initials: A
authors.lastname: Kick
authors.forename: Raffaela
authors.initials: R
authors.lastname: Bertoli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Moschovitis
authors.forename: Pia
authors.initials: P
authors.lastname: Caduff Janosa
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
mesh_terms: D000208:Acute Disease; D000700:Analgesics / Q000009:adverse effects* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D001919:Bradycardia / Q000139:chemically induced* / Q000175:diagnosis; D003000:Clonidine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D004347:Drug Interactions; D004562:Electrocardiography; D004630:Emergencies; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000175:diagnosis; D006760:Hospitalization; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D007902:Length of Stay; D017116:Low Back Pain / Q000188:drug therapy*; D008875:Middle Aged; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; C023754:tizanidine; D003000:Clonidine