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

• 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
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1592/phco.2005.25.9.1271

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.