cositis is present, until there is evidence of healing
persistent pleural effusion is present; this should be drained dry prior to infusion.
Adequate renal function must be documented.
-
Serum creatinine must be normal, and creatinine clearance must be greater than 60 mL/min, before initiation of therapy.
-
Serum creatinine must be measured prior to each subsequent course of therapy. If serum creatinine has increased by 50% or more compared to a prior value, the creatinine clearance must be measured and documented to be greater than 60 mL/min (even if the serum creatinine is still within the normal range).
Patients must be well hydrated, and must be treated with sodium bicarbonate for urinary alkalinization.
-
Administer 1,000 mL/m2 of intravenous fluid over 6 hours prior to initiation for the methotrexate infusion. Continue hydration at 125 mL/m2/hr (3 liters/m2/day) during the methotrexate infusion, and for 2 days after the infusion has been completed.
-
Alkalinize urine to maintain pH above 7.0 during methotrexate infusion and leucovorin calcium therapy. This can be accomplished by the administration of sodium bicarbonate orally or by incorporation into a separate intravenous solution.
Repeat serum creatinine and serum methotrexate 24 hours after starting methotrexate and at least once daily until the methotrexate level is below 5 × 10-8 mol/L (0.05 micromolar).
The table below provides guidelines for leucovorin calcium dosage based upon serum methotrexate levels. (See table below.‡)
Patients who experience delayed early methotrexate elimination are likely to develop nonreversible oliguric renal failure. In addition to appropriate leucovorin therapy, these patients require continuing hydration and urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved. If necessary, acute, intermittent hemodialysis with a high-flux dialyzer may also be beneficial in these patients.
Some patients will have abnormalities in methotrexate elimination, or abnormalities in renal function following methotrexate administration, which are significant but less severe than the abnormalities described in the table below. These abnormalities may or may not be associated with significant clinical toxicity. If significant toxicity is observed, leucovorin rescue should be extended for an additional 24 hours (total 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate binding to serum albumin, or elimination) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.
CAUTION: DO NOT ADMINISTER LEUCOVORIN INTRATHECALLY.
Psoriasis, Rheumatoid Arthritis, and Juvenile Rheumatoid Arthritis
Adult Rheumatoid Arthritis
Recommended Starting Dosage Schedules
-
Single oral doses of 7.5 mg once weekly.1
-
Divided oral dosages of 2.5 mg at 12 hour intervals for 3 doses given as a course once weekly.1
Polyarticular-Course Juvenile Rheumatoid Arthritis
The recomm |
