Drug Detail:Leucovorin (injection) (Leucovorin (injection) [ loo-koe-vor-in ])
Drug Class: Antidotes
Usual Adult Dose for Colorectal Cancer
200 mg/m2, by slow IV injection (minimum 3 minutes), followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days
OR
20 mg/m2, IV, followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days
Comments:
- Do not be mix in the same infusion as 5-fluorouracil; a precipitate may form.
- May repeat 5 day treatment course at 4 week (28 day) intervals for 2 courses, then repeat at 4 to 5 week (28 to 35 day) intervals provided the patient is completely recovered from toxicities of the prior course.
Use: For use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
Usual Adult Dose for Methotrexate Rescue
Leucovorin Rescue:
15 mg (approximately 10 mg/m2), orally, IV, or IM, every 6 hours for 10 doses; start 24 hours after beginning of methotrexate infusion (based on a methotrexate dose of 12 to 15 g/m2 IV over 4 hours)
Impaired Methotrexate Elimination or Inadvertent Overdosage:
10 mg/m2 orally, IV, or IM, every 6 hours until methotrexate level is less than 10(-8) mol
Comments:
- Determine serum creatinine and methotrexate levels at least once a day.
- Continue leucovorin, hydration, and urinary alkalization until methotrexate levels are below 5 x 10(-8) mol.
- Give parenterally if gastrointestinal toxicity, nausea, or vomiting are present.
Uses: Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages.
Usual Adult Dose for Methotrexate Overdosage
Leucovorin Rescue:
15 mg (approximately 10 mg/m2), orally, IV, or IM, every 6 hours for 10 doses; start 24 hours after beginning of methotrexate infusion (based on a methotrexate dose of 12 to 15 g/m2 IV over 4 hours)
Impaired Methotrexate Elimination or Inadvertent Overdosage:
10 mg/m2 orally, IV, or IM, every 6 hours until methotrexate level is less than 10(-8) mol
Comments:
- Determine serum creatinine and methotrexate levels at least once a day.
- Continue leucovorin, hydration, and urinary alkalization until methotrexate levels are below 5 x 10(-8) mol.
- Give parenterally if gastrointestinal toxicity, nausea, or vomiting are present.
Uses: Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages.
Usual Adult Dose for Megaloblastic Anemia
Up to 1 mg, IV or IM, once a day
Comments:
- There is no evidence that doses above 1 mg daily have greater efficacy; additionally, urinary folate loss becomes roughly logarithmic as the amount administered exceeds 1 mg.
Use: Treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible
Usual Adult Dose for Folic Acid Antagonist Overdose
5 to 15 mg orally once a day
Use: Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists.
Usual Adult Dose for Pneumocystis Pneumonia
Treatment of pneumocystis pneumonia is not is not a labeled indication.
20 mg/m2 or 0.5 mg/kg, IV or orally, every 6 hours, continued for 3 days after last trimetrexate dose
Comments:
- Use in combination with trimetrexate.
Use: Treatment of pneumocystis pneumonia in HIV infected patients
Usual Adult Dose for Pneumocystis Pneumonia Prophylaxis
Prophylaxis of pneumocystis pneumonia is not a labeled indication.
25 mg, orally, once a week, in combination with dapsone and pyrimethamine
Comments:
- Prophylaxis in HIV infected patients usually begins when the CD4+ count is less than 200 cells/mm or for a history of oropharyngeal candidiasis.
- Prophylaxis is usually discontinued when CD4+ count is 200 cells/mm or higher for 3 months.
Use: Pneumocystis pneumonia prophylaxis in immunocompromised patients
Usual Adult Dose for Toxoplasmosis
Use in the treatment of toxoplasmosis is not a labeled indication.
Ocular toxoplasmosis:
5 to 25 mg orally, IV, or IM, with each dose of pyrimethamine
Acute/primary treatment of toxoplasma encephalitis in AIDS patients:
Standard dose: 10 to 20 mg, orally, IM, or IV, once a day, during and for 1 week after pyrimethamine treatment
Maximum dose: 50 mg once a day
Use: Toxoplasmosis treatment
Usual Pediatric Dose for Colorectal Cancer
200 mg/m2, by slow IV injection (minimum 3 minutes), followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days
OR
20 mg/m2, IV, followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days
Comments:
- Do not be mix in the same infusion as 5-fluorouracil; a precipitate may form.
- May repeat 5 day treatment course at 4 week (28 day) intervals for 2 courses, then repeat at 4 to 5 week (28 to 35 day) intervals provided the patient is completely recovered from toxicities of the prior course.
Use: For use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
Usual Pediatric Dose for Methotrexate Rescue
Leucovorin Rescue:
15 mg (approximately 10 mg/m2), orally, IV, or IM, every 6 hours for 10 doses; start 24 hours after beginning of methotrexate infusion (based on a methotrexate dose of 12 to 15 g/m2 IV over 4 hours)
Impaired Methotrexate Elimination or Inadvertent Overdosage:
10 mg/m2 orally, IV, or IM, every 6 hours until methotrexate level is less than 10(-8) mol
Comments:
- Determine serum creatinine and methotrexate levels at least once a day.
- Continue leucovorin, hydration, and urinary alkalization until methotrexate levels are below 0.05 micromol.
- Give parenterally if gastrointestinal toxicity, nausea, or vomiting are present.
Uses: Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages.
Usual Pediatric Dose for Megaloblastic Anemia
Up to 1 mg, IV or IM, once a day
Comments:
- There is no evidence that doses above 1 mg daily have greater efficacy; additionally, urinary folate loss becomes roughly logarithmic as the amount administered exceeds 1 mg.
Use: Treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible
Usual Pediatric Dose for Folic Acid Antagonist Overdose
5 to 15 mg orally once a day
Use: Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists.
Renal Dose Adjustments
Data not available
Liver Dose Adjustments
Data not available
Dose Adjustments
Leucovorin Rescue for Methotrexate (MTX):
- Normal MTX elimination (MTX approximately 10 micromol 24 hours after administration, 1 micromol at 48 hours, and less than 0.2 micromol at 72 hours): Leucovorin 15 mg oral, IM, or IV every 6 hours for 60 hours (10 doses)
- Delayed late MTX elimination (MTX above 0.2 micromol at 72 hours, and more than 0.05 micromol at 96 hours): Continue 15 mg orally, IM, or IV every 6 hours until MTX level is under 0.05 micromol
- Delayed early MTX elimination and/or acute renal injury (MTX 50 micromol or higher at 24 hours, or 5 micromol at 48 hours, OR a 100% or greater increase in serum creatinine at 24 hours): 150 mg leucovorin IV every 3 hours, until MTX is less than 1 micromol; then 15 mg IV every 3 hours until MTX is less than 0.05 micromol.
- Patients with delayed early methotrexate elimination are likely to develop reversible renal failure; continue hydration, and urinary alkalization, and close monitoring of fluid and electrolytes, in addition to leucovorin, until MTX level is below 0.05 micromol and renal failure has resolved.
- Abnormalities in MTX elimination or renal function, which are significant but less severe than abnormalities described above, may or may not be associated with significant clinical toxicity.
- If significant clinical toxicity is observed, extend leucovorin rescue for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy.
- Consider the possibility that the patient is taking other medications which interact with MTX when laboratory abnormalities or clinical toxicities are observed.
Impaired Methotrexate Elimination or Inadvertent Overdosage:
- If the 24 hour serum creatinine has increased 50% over baseline, or if the 24 hour MTX level is higher than 9 x 10(-7) mol, increase leucovorin dose to 100 mg/m2 IV every 3 hours until MTX level is less than 10(-8) mol.
- Hydration and urinary alkalinization should be used concomitantly with leucovorin.
Colorectal Cancer:
- After the initial treatment, adjust the dosage of 5-fluorouracil based on patient tolerance and prior treatment course.
- Do not adjust leucovorin dose for toxicity.
Dialysis
Data not available
Other Comments
Administration advice:
- Do not administer intrathecally; may be harmful or fatal if given intrathecally.
- Because of the calcium content of the solution, no more than 160 mg should be injected intravenously per minute (16 mL of a 10 mg/mL, or 8 mL of a 20 mg/mL solution per minute).
Reconstitution/preparation techniques:
- Because of the benzyl alcohol in certain diluents, when administering doses greater than 10 mg/m2, reconstitute with Sterile Water for Injection, USP, and use immediately.
IV compatibility:
- Do not mix in the same infusion as fluorouracil; a precipitate may form.
