Brand name: methotrexate
Generic name: Methoblastin, amethopterin, Rheumatrex, Emthexate, MTX

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Patients treated with methotrexate should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Duration of leucovorin administration varies with the dosage of methotrexate and plasma concentrations achieved (including rate of elimination); in general, leucovorin administration is continued until methotrexate concentrations fall to less than 5 � 10 -8 Molar. Her RA had been treated with methotrexate (10 mg per week) and bucillamine (200 mg per day) for 6 years. May aid in identifying patients with delayed methotrexate clearance; toxicity appears to be related at least as much to the length of time that methotrexate concentrations are elevated as to the peak concentrations achieved. Methotrexate, especially at higher doses or with prolonged treatment, has been associated with hepatotoxicity including acute hepatitis, chronic fibrosis, necrosis, cirrhosis, and liver enzyme elevations. In patients receiving concomitant methotrexate, the incidence was 6% compared to 26% with Humira monotherapy. Alkalinization of urine (with bicarbonate and/or acetazolamide) and intravenous hydration (1000 mL per square meter of body surface area over six hours prior to beginning the methotrexate infusion and 3000 mL per square meter of body surface area per day during the methotrexate infusion and for two days after the infusion is completed) are also important to prevent renal toxicity caused by methotrexate and/or its metabolites. It is recommended that duration of leucovorin administration in these patients be based on determination of plasma methotrexate concentrations. Leucovorin also is indicated as a rescue after high-dose methotrexate therapy in osteosarcoma and as a part of chemotherapeutic treatment programs in the management of several forms of cancer. Leucovorin given at the appropriate time rescues bone marrow and gastrointestinal cells from methotrexate but has no apparent effect on pre-existing methotrexate nephrotoxicity. In patients with psoriatic arthritis, the rate of antibody development in patients receiving Humira monotherapy was comparable to patients with rheumatoid arthritis; however, in patients receiving concomitant methotrexate the rate was 7% compared to 1% in rheumatoid arthritis.

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