Is methotrexate treatment associated with a risk of cardiomyopathy?/nThe question concerns a 66-yea

Fråga: Is methotrexate treatment associated with a risk of cardiomyopathy? The question concerns a 66-year-old woman with long-standing seropositive rheumatoid arthritis. Since 1998 she has been treated with 12.5 mg of methothrexate weekly. No other disease modifying anti-rheumatic drugs have been used. In October 2003 an asymptomatic left ventricular dilatation and dysfunction was found, with an ejection fraction of 20%. The etiology of the finding is unclear.

Sammanfattning: Though there are rare cases of possible methotrexate-induced cardiotoxicity, the published literature does not support methotrexate as a likely cause of dilated cardiomyopathy.

Svar: Methotrexate is a cytotoxic agent targeting the folate metabolism, used in high dosages against neoplastic disease and in substantially lower doses, such as that of the present patient, as an antirheumatic agent (1). Standard textbooks do not cite cardiotoxicity as a known side effect of metothrexate treatment (2,3). The cardiotoxicity of methotrexate has been dealt with in a previous Drugline document. A few cases where metothrexate precipitated frequent ventricular extrasystoles in patients with underlying heart disease were reviewed, as well as two cases of possible methotrexate-associated exudative pericarditis (4). An updated Medline search did not identify any further reports.

The Swedish adverse drug reaction register (SADRAC) cites three cases of cardiomyopathy or heart failure as metothrexate side effects. However, one of these patients was on cancer chemotherapy, and was also treated with doxorubicin (a known cardiotoxic substance), one had a known underlying ischemic heart disease and in the third case it is not evident that the patient had heart failure at all.

If no other cause of cardiomyopathy is found we recommend that this case be reported to the regional centre of SADRAC (Swedish Adverse Drug Reactions Advisory Committee).