travenous fluid over 6 hours prior to initiation of 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 5x10-8 mol/L (0.05 micromolar).
The table below provides guidelines for leucovorin calcium dosage based upon serum methotrexate levels. (See table LEUCOVORIN RESCUE SCHEDULES FOLLOWING TREATMENT WITH HIGHER DOSES OF METHOTREXATE )
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 clinical 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.
Divided oral dosages of 2.5 mg at 12 hour intervals for 3 doses given as a course once weekly.
Methotrexate Sodium Tablets for oral administration are available.
Polyarticular-Course Juvenile Rheumatoid Arthritis: The recommended starting dose is 10 mg/m2 given once weekly.
For either adult RA or polyarticular-course JRA dosages may be adjusted gradually to achieve an optimal response. Limited experience shows a significant increase in the incidence and severity of serious toxic reactions, especially bone marrow suppression, at doses greater than 20 mg/wk in adults. Although there is experience with doses up to 30 mg/m2/wk in children, there are too few published data to assess how doses over 20 mg/m2/wk might affect the risk of serious toxicity in children. Experience does suggest, however, that children receiving 20 to 30 mg/m2/wk (0.65 to 1 mg/kg/wk) may have better absorption and fewer gastrointestinal side effects if methotrexate is administered either intramuscularly or subcutaneously.
Therapeutic response usually begins within 3 to 6 weeks and the patient may c |
