Acute Cardiac Toxicity Associated with High‐Dose Intravenous Methotrexate Therapy: Case Report and Review of the Literature

A 36‐year‐old woman was hospitalized for preoperative chemotherapy for osteosarcoma. She received intravenous fluids for 12 hours for volume expansion, then methotrexate 24 g (12 g/m2) over 6 hours. This was followed by intravenous leucovorin 200 mg over 1 hour. Two hours after the methotrexate infu...

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Bibliographic Details
Published in:Pharmacotherapy 2005-09, Vol.25 (9), p.1271-1276
Main Authors: Perez‐Verdia, Alejandro, Angulo, Freddy, Hardwicke, Fred L., Nugent, Kenneth M.
Format: Article
Language:English
Subjects:
Adult
Antimetabolites, Antineoplastic - administration & dosage
Antimetabolites, Antineoplastic - adverse effects
Antimetabolites, Antineoplastic - therapeutic use
arrhythmia
Bradycardia - chemically induced
cardiac toxicity
Electrocardiography
Fatal Outcome
Female
high‐dose methotrexate
Humans
Infusions, Intravenous
Leucovorin - therapeutic use
Methotrexate - administration & dosage
Methotrexate - adverse effects
Methotrexate - therapeutic use
Osteosarcoma - drug therapy
Spinal Neoplasms - drug therapy
Tachycardia, Ventricular - chemically induced
Vitamin B Complex - therapeutic use
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Summary:A 36‐year‐old woman was hospitalized for preoperative chemotherapy for osteosarcoma. She received intravenous fluids for 12 hours for volume expansion, then methotrexate 24 g (12 g/m2) over 6 hours. This was followed by intravenous leucovorin 200 mg over 1 hour. Two hours after the methotrexate infusion the patient developed chest pain and bradycardia. An electrocardiogram revealed sinus pauses, and telemetry recordings indicated a 4‐beat run of ventricular tachycardia. A cardiac work‐up consisting of cardiac enzyme level determination, two‐dimensional echocardiography, and an adenosine technetium‐99m tetrofosmin stress test was negative for structural and ischemic heart disease. The patient recovered without treatment and, approximately 2 weeks later, received a second course of methotrexate at half the dose without complication. One month later the patient received treatment with doxorubicin and cisplatin; 2 days later she died unexpectedly at home. Clinicians should be aware that high‐dose methotrexate can cause cardiac symptoms and arrhythmias in previously healthy adults. This complication warrants attention and needs additional clinical investigation.
ISSN:0277-0008
1875-9114
DOI:10.1592/phco.2005.25.9.1271