West identified factors associated with an increased risk for hepatotoxicity in a patient receiving methotrexate therapy.



Strong Association

Probable Association

Possible Association

methotrexate dosing

daily dosing

duration of therapy > 2 years; cumulative dose > 1,500 mg

maximum weekly dose > 25 mg

concurrent disease

renal insufficiency

obesity and diabetes mellitus

obesity or diabetes mellitus alone

concurrent liver disease

pre-existing liver disease; previous or concurrent heavy ethanol use


heterozygous alpha-1 antitrypsin deficiency; Felty's syndrome


Therapies increasing risk:

(1) concurrent NSAID use (potential)

(2) concurrent cyclosporine (potential)

(3) concurrent PUVA therapy (potential)

(4) previous therapy with vitamin A (potential)

(5) previous therapy with arsenicals (probable)


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