Risk Factors for Methotrexate Hepatotoxicity

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

Parameter	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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Purpose: To evaluate a patient taking methotrexate for risk factors associated with hepatoxicity.