l. 1 concomitant granulocytopenia and fever were present in some but not all of the patients. the concomitant use of leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of pneumocystis carinii pneumonia in patients with hiv infection was associated with increased rates of treatment failure and mortality in a placebo-controlled study.

mg (100 mg/m 2 ) iv every 3 hours until the methotrexate level is less than 10 -8 m. doses greater than 25 mg should be given parenterally (see clinical pharmacology ). hydration (3 l/d) and urinary alkalinization with sodium bicarbonate should be employed concomitantly. the bicarbonate dose should be adjusted to maintain the urine ph at 7.0 or greater. the recommended dose of leucovorin to counteract hematologic toxicity from folic acid antagonists with less affinity for mammalian dihydrofolate reductase than methotrexate (i.e., trimethoprim, pyrimethamine) is substantially less, and 5 to 15 mg of leucovorin per day has been recommended by some investigators. patients who experience delayed early methotrexate elimination are likely to develop reversible non-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 below 0.05 micromolar and the renal failure has resolved. some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe. 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 elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.

± 0.08 hours, b) peak serum folate concentration achieved: 268 ± 18 ng/ml, c) serum folate half-disappearance time: 3.5 hours. oral tablets yielded areas under the serum folate concentration-time curves (aucs) that were 12% greater than equal amounts of leucovorin given intramuscularly and equal to the same amounts given intravenously. oral absorption of leucovorin is saturable at doses above 25 mg. the apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg and 37% for 100 mg.

blets store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] protect from light and moisture. references 1. grem jl, shoemaker dd, petrelli nj, douglas ho. severe and fatal toxic effects observed in treatment with high- and low-dose leucovorin plus 5-fluorouracil for colorectal carcinoma. cancer treat rep 1987;71:1122. 2. link mp, goorin am, miser aw et al. the effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. n engl j med 1986;314:1600-1606. distr. by: west-ward pharmaceuticals corp. eatontown, nj 07724 4055309//07 revised october 2020