Leucovorin calcium
(Citrovorum factor, Folinic acid)
Leucovorin calcium (Wellcovorin)
Citrovorum factor (Wellcovorin)
Folinic acid (Wellcovorin)
Leucovorin Calcium
(loo-koh- VOR-in)
Pregnancy Category: C Lederle Leucovorin Calcium Wellcovorin (Rx)

Classification: Folic acid derivative

Action/Kinetics: Derivative of folic acid; is a mixture of the diasterioisomers of the 5-formyl derivative of tetrahydrofolic acid. Does not require reduction by dihydrofolate reductase to be active in intracellular metabolism; thus, it is not affected by dihydrofolate inhibitors. Rapidly absorbed following PO administration. Quickly metabolized to 1,5-methyltetrahydrofolate, which is then metabolized by other pathways back to 5,10-methylene-tetrahydrofolate and then converted to 5-methyltetrahydrofolate using the cofactors FADH ₂ and NADPH. Leucovorin can counteract the therapeutic and toxic effects of methotrexate (acts by inhibiting dihydrofolate reductase) but can enhance the effects of 5-fluorouracil (5-FU). Is rapidly absorbed. Peak serum levels, PO: Approximately 2.3 hr; after IM: 52 min; after IV: 10 min. Onset, PO: 20-30 min; IM: 10-20 min; IV: < 5 min. Terminal t 1/2: 5.7 hr (PO), 6.2 hr (IM and IV). Duration: 3-6 hr. Excreted by the kidney.

Uses: PO and Parenteral: Prophylaxis and treatment of toxicity due to methotrexate and folic acid antagonists (e.g., pyrimethamine and trimethoprim). Leucovorin rescue following high doses of methotrexate for osteosarcoma. Parenteral: Megaloblastic anemias due to nutritional deficiency, sprue, pregnancy, and infancy when oral folic acid is not appropriate. Adjunct with 5-FU to prolong survival in the palliative treatment of metastatic colorectal carcinoma. Note: It is recommended for megaloblastic anemia caused by pregnancy even though the drug is pregnancy category C.

Contraindications: Pernicious anemia or megaloblastic anemia due to vitamin B ₁₂ deficiency.

Special Concerns: Use with caution during lactation. May increase the frequency of seizures in susceptible children. When leucovorin is used with 5-FU for advanced colorectal cancer, the dosage of 5-FU must be lower than usual as leucovorin enhances the toxicity of 5-FU. The benzyl alcohol in the parenteral form may caues a fatal gasping syndrome in premature infants.

Side Effects: Leucovorin alone. Allergic reactions, including urticaria and anaphylaxis.
Leucovorin and 5-FU. G I: N&V;, diarrhea, stomatitis, constipation, anorexia. Hematologic: Leukopenia, thrombocytopenia. CNS: Fatigue, lethargy, malaise. Miscellaneous: Infection, alopecia, dermatitis.

Drug Interactions: 5-FU / 5-FU toxicity Methotrexate / High doses effect of intrathecal methotrexate PAS / Serum folate levels folic acid deficiency Phenobarbital / Phenobarabital effect seizure frequency, especially in children Phenytoin / Phenytoin effect R/T rate of liver breakdown; also, drug may plasma folate levels Primidone / Primidone effect seizure frequency, especially in children Sulfasalazine / Serum folate levels folic acid deficiency

How Supplied: Injection: 10 mg/mL; Powder for injection: 50 mg, 100 mg, 200 mg, 350 mg; Tablet: 5 mg, 10 mg, 15 mg, 25 mg

Dosage
?IM, IV, Tablets Advanced colorectal cancer.
Either leucovorin, 200 mg/m ² by slow IV over a minimum of 3 min followed by 5-FU, 370 mg/m ² IV or leucovorin 20 mg/m ² IV followed by 5-FU, 425 mg/m ² IV. Treatment is repeated daily for 5 days with the 5-day treatment course repeated at 28-day intervals for two courses and then repeated at 4- to 5-week intervals as long as the client has recovered from the toxic effects.
Leucovorin rescue after high-dose methotrexate therapy.
The dose of leucovorin is based on a methotrexate dose of 12-15 mg/m ² given by IV infusion over 4 hr. The dose of leucovorin is 15 mg (10 mg/m ²) PO, IM, or IV q 6 hr for 10 doses starting 24 hr after the start of the methotrexate infusion. Give leucovorin parenterally if there is nausea, vomiting, or GI toxicity. If serum methotrexate levels are greater than 0.2 üM at 72 hr and greater than 0.05 üM at 96 hr after administration, leucovorin should be continued at a dose of 15 mg PO, IM, or IV q 6 hr until methotrexate levels are less than 0.05 üM. If serum methotrexate levels are equal to or greater than 50 üM at 24 hr or equal to or greater than 5 üM at 48 hr after administration or if there is a 100% or greater increase in serum creatinine levels at 24 hr after methotrexate administration, the dose of leucovorin should be 150 mg IV q 3 hr until methotrexate levels are less than 1 üM; then, give leucovorin, 15 mg IV q 3 hr until methotrexate levels are less than 0.05 üM. If significant clinical toxicity is seen following methotrexate, leucovorin rescue should total 14 doses over 84 hr in subsequent courses of methotrexate therapy.
Impaired methotrexate elimination or accidental overdose.
Start leucovorin rescue as soon as the overdose is discovered and within 24 hr of methotrexate administration when excretion is impaired. Give leucovorin, 10 mg/m ² PO, IM, or IV q 6 hr until serum methotrexate levels are less than 10 ^-8 M. If the 24-hr serum creatinine has increased 50% over baseline or if the 24- or 48-hr methotrexate level is more than 5 x 10 ^-6 M or greater than 9 x 10 ^-7 M, respectively, the dose of leucovorin should be increased to 100 mg/m ² IV q 3 hr until the methotrexate level is less than 10 ^-8 M. Urinary alkalinization with sodium bicarbonate solution (to maintain urine pH at 7 or greater) and hydration with 3 L/day should be undertaken at the same time.
Overdosage of folic acid antagonists.
5-15 mg/day.
Megaloblastic anemia due to folic acid deficiency.
Adults and children: Up to 1 mg/day.