Tolterodine-associated acute mixed liver injury.
OBJECTIVE
To report a patient with an acute mixed liver injury associated with tolterodine therapy.


METHODS
An 81-year-old white woman with urge incontinence experienced malaise, fever, and gastrointestinal disturbances 18 days after starting tolterodine 2 mg twice daily. The patient's concurrent medications included flunitrazepam, diclofenac, and dorzolamide/timolol eye drops. Laboratory examination was consistent with the presentation of an acute mixed liver injury with increased transaminase enzymes, alkaline phosphatase, gamma-glutamyltransferase, and bilirubin. Additionally, she had mild leukocytosis with eosinophilia. After tolterodine was discontinued, the abnormal liver and hematologic parameters returned to normal within 4 weeks.


CONCLUSIONS
Tolterodine, a muscarinic receptor antagonist, has predominantly anticholinergic effects. To our knowledge, this is the first case published describing tolterodine-associated acute mixed liver injury. However, some of the patient's additional symptoms can also be considered part of a drug-induced hypersensitivity syndrome. This is usually defined by the triad of fever, cutaneous reaction, and involvement of internal organs, mainly affecting the liver. The close temporal relationship between the start of tolterodine therapy and the first symptoms and the reversibility after dechallenge led us to conclude that the adverse reaction was possibly related to tolterodine exposure.


CONCLUSIONS
Our case illustrates that tolterodine may rarely be associated with liver injury. This may have been an organ manifestation of tolterodine-induced hypersensitivity syndrome.
Schlienger
Raymond G
RG
Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. schliengerr@uhbs.ch
Keller
Martin J
MJ
Krähenbühl
Stephan
S
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D003408:Cresols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced*; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; D000637:Transaminases / Q000097:blood / Q000187:drug effects; D014549:Urinary Incontinence / Q000188:drug therapy; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000187:drug effects
D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; D005723:gamma-Glutamyltransferase; D000637:Transaminases; D000469:Alkaline Phosphatase; D001663:Bilirubin