The Drug-Induced Cardiotoxicity Website and App

Frequency - Incidence

Incidence of cardiac adverse event(s) due to the specific drug as assessed by number of reported/published cases in the literature. Red digits in stars indicate: 0 = Very rare, questionable signal · 1 = < 10 cases · 2 = 10-50 cases · 3 = 50–100 cases · 4 = 100-200 cases · 5 = >200 cases

Evidence level/grade

Evidence level for cardiac adverse event(s) due to the specific drug as estimated using Hill’s (1965), Naranjo’s (1981), and Bégaud’s (1985) criteria applied to published cases. Blue digits in stars indicate: 0 = Questionable · 1 = Low · 2 = Moderate · 3 = Robust · 4 = Definite · 5 = Unquestionable, pathognomonic

XXIV.b

Pneumonitis (ILD), acute and/or severe (may produce the ARDS pattern)

A common cause of fulminant respiratory failure in RA. Careful exclusion of Pneumocystis pneumonia is always necessary

Publications

Gökten DB, Mercan R

Methotrexate-Associated Hypersensitivity Pneumonitis After 15 Years of Use: A Case Report and Literature Review.

Mediterranean journal of rheumatology. 2025;36(2):316-321

Liu YC, Tu YL, Wu RC, Huang JL, Yao TC

Life-threatening pneumonitis complicating low-dose methotrexate treatment for juvenile idiopathic arthritis in a child.

Pediatric emergency care. 2014;30(6):415-7

D'Elia T

Methotrexate-induced pneumonitis: heterogeneity of bronchoalveolar lavage and differences between cancer and rheumatoid arthritis.

Inflammation & allergy drug targets. 2014;13(1):25-33

Kakavas S, Balis E, Lazarou V, Kouvela M, Tatsis G

Respiratory failure due to infliximab induced interstitial lung disease.

Heart & lung : the journal of critical care. 2013;42(6):480-2

Saigal S, Singh RK, Poddar B

Acute methotrexate toxicity presenting as multiorgan failure and acute pneumonitis: A rare case report.

Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2012;16(4):225-7

Sathi N, Chikura B, Kaushik VV, Wiswell R, Dawson JK

How common is methotrexate pneumonitis? A large prospective study investigates.

Clinical rheumatology. 2012;31(1):79-83

Brechmann T, Heyer C, Schmiegel W

[Methotrexate-induced pneumonitis in a woman with Crohn's disease].

Deutsche medizinische Wochenschrift (1946). 2007;132(34-35):1759-62

Müller KM, Einsfelder BM

[Drug-induced pulmonary damage].

Der Pathologe. 2006;27(1):19-26

Lateef O, Shakoor N, Balk RA

Methotrexate pulmonary toxicity.

Expert opinion on drug safety. 2005;4(4):723-30

Kinder AJ, Hassell AB, Brand J, Brownfield A, Grove M, Shadforth MF

The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions.

Rheumatology (Oxford, England). 2005;44(1):61-6

Arakawa H, Yamasaki M, Kurihara Y, Yamada H, Nakajima Y

Methotrexate-induced pulmonary injury: serial CT findings.

Journal of thoracic imaging. 2003;18(4):231-6

Kramer N, Chuzhin Y, Kaufman LD, Ritter JM, Rosenstein ED

Methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid arthritis.

Arthritis and rheumatism. 2002;47(6):670-1

Fuhrman C, Parrot A, Wislez M, Prigent H, Boussaud V, Bernaudin JF, Mayaud C, Cadranel J

Spectrum of CD4 to CD8 T-cell ratios in lymphocytic alveolitis associated with methotrexate-induced pneumonitis.

American journal of respiratory and critical care medicine. 2001;164(7):1186-91

Zisman DA, McCune WJ, Tino G, Lynch JP 3rd

Drug-induced pneumonitis: the role of methotrexate.

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG. 2001;18(3):243-52

Imokawa S, Colby TV, Leslie KO, Helmers RA

Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients.

The European respiratory journal. 2000;15(2):373-81

Ohosone Y, Okano Y, Kameda H, Fujii T, Hama N, Hirakata M, Mimori T, Akizuki M, Ikeda Y

Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pneumonitis.

The Journal of rheumatology. 1997;24(12):2299-303

Cannon GW

Methotrexate pulmonary toxicity.

Rheumatic diseases clinics of North America. 1997;23(4):917-37

Kremer JM, Alarcón GS, Weinblatt ME, Kaymakcian MV, Macaluso M, Cannon GW, Palmer WR, Sundy JS, St Clair EW, Alexander RW, Smith GJ, Axiotis CA

Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review.

Arthritis and rheumatism. 1997;40(10):1829-37

Alarcón GS, Kremer JM, Macaluso M, Weinblatt ME, Cannon GW, Palmer WR, St Clair EW, Sundy JS, Alexander RW, Smith GJ, Axiotis CA

Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group.

Annals of internal medicine. 1997;127(5):356-64

Salaffi F, Manganelli P, Carotti M, Subiaco S, Lamanna G, Cervini C

Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: report of five cases and review of the literature.

Clinical rheumatology. 1997;16(3):296-304

Barrera P, Laan RF, van Riel PL, Dekhuijzen PN, Boerbooms AM, van de Putte LB

Methotrexate-related pulmonary complications in rheumatoid arthritis.

Annals of the rheumatic diseases. 1994;53(7):434-9

Whitcomb ME, Schwarz MI, Tormey DC

Methotrexate pneumonitis: case report and review of the literature.

Thorax. 1972;27(5):636-9

Shapiro CL, Yeap BY, Godleski J, Jochelson MS, Shipp MA, Skarin AT, Canellos GP

Drug-related pulmonary toxicity in non-Hodgkin's lymphoma. Comparative results with three different treatment regimens.

Cancer. 1991;68(4):699-705

Hargreaves MR, Mowat AG, Benson MK

Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis: report of five cases and review of published reports.

Thorax. 1992;47(8):628-33

Manni JJ, Van den Broek P

Pulmonary complications of methotrexate therapy.

Clinical otolaryngology and allied sciences. 1977;2(2):131-7

Lascari AD, Strano AJ, Johnson WW, Collins JG

Methotrexate-induced sudden fatal pulmonary reaction.

Cancer. 1977;40(4):1393-7