Leucovorin Calcium

Storage

Oral

15–30°C.b Protect from light and moisture.b

Parenteral

2–8°C.c Protect from light; retain in original carton until time of use.c Discard unused portion.c

15–30°C.a c Protect from light.a c

Following reconstitution with sterile water for injection, use immediately and discard unused portion.102 c

Following reconstitution with bacteriostatic water for injection, use within 7 days.102 c

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

• Antidote
• Chemotherapy Modulating Agent
• Rescue Agent (Chemotherapy)
• Vitamin, Water Soluble

Adjunctive cofactor therapy in methanol toxicity

Based on the American Academy of Clinical Toxicology guidelines for the treatment of methanol poisoning, leucovorin calcium given as adjunctive cofactor therapy to aid in the elimination of formic acid in methanol-poisoned patients is effective and recommended in the management of these patients [AACT [Barceloux 2002]].

Bladder cancer (neoadjuvant treatment)

Data from a large international phase III study support the use of leucovorin calcium (as methotrexate rescue; in combination with cisplatin, vinblastine, and methotrexate) for neoadjuvant treatment of muscle invasive bladder cancer [Griffiths 2011].

Esophageal cancer (advanced or metastatic)

Data from a randomized phase III study support the use of leucovorin calcium (in combination with fluorouracil and irinotecan [FOLFIRI]) for the treatment of locally advanced or metastatic adenocarcinoma of the esophagogastric junction [Guimbaud 2014]. Data from a randomized phase III study supports the use of leucovorin calcium (in combination with fluorouracil and oxaliplatin) for the treatment of locally advanced or metastatic adenocarcinoma of the esophagogastric junction [Al-Batran 2008].

Gastric cancer (advanced or metastatic)

Data from a randomized phase III study support the use of leucovorin calcium (in combination with fluorouracil and irinotecan [FOLFIRI]) for the treatment of locally advanced or metastatic gastric adenocarcinoma [Guimbaud 2014]. Data from a randomized phase III study supports the use of leucovorin calcium (in combination with fluorouracil and oxaliplatin) for the treatment of locally advanced or metastatic gastric cancer [Al-Batran 2008].

Pancreatic cancer (metastatic)

Data from a phase II/III randomized trial support the use of leucovorin calcium (in combination with fluorouracil, oxaliplatin, and irinotecan; FOLFIRINOX regimen) in the management of patients with metastatic pancreatic cancer [Conroy 2011].

Prevention of pyrimethamine hematologic toxicity in HIV-exposed/-positive patients (children)

Based on the Centers for Disease Control and Prevention (CDC) Prevention and Treatment of Opportunistic Infections Guidelines (children), leucovorin is effective and recommended for the prevention of pyrimethamine hematologic toxicity in HIV-exposed/-positive patients [CDC 2009].

Prevention of pyrimethamine hematologic toxicity in HIV-infected patients (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, leucovorin is effective and recommended for the prevention of pyrimethamine hematologic toxicity in adolescent and adult HIV-infected patients.

Pernicious anemia and other megaloblastic anemias secondary to vitamin B12-deficiency

Folic acid antagonist (eg, trimethoprim, pyrimethamine) overdose: Refer to adult dosing.

Folate-deficient megaloblastic anemia: Refer to adult dosing.

High-dose methotrexate-rescue: Refer to adult dosing.

Cofactor therapy in methanol toxicity (off-label use): Refer to adult dosing.

Prevention of pyrimethamine hematologic toxicity in HIV-exposed/-positive patients (off-label uses; CDC, 2009):

Infants and Children >1 month of age: Note: Leucovorin should continue for 1 week after pyrimethamine is discontinued.

Toxoplasmosis (Toxoplasma gondii):

Primary prophylaxis: Oral: 5 mg once every 3 days (in combination with pyrimethamine [with either dapsone or atovaquone])

Secondary prophylaxis: Oral: 5 mg once every 3 days (in combination with pyrimethamine [with either sulfadiazine, atovaquone, or clindamycin])

Treatment (congenital): Oral or IM: 10 mg with every pyrimethamine dose (in combination with either sulfadiazine or clindamycin); treatment duration: 12 months

Treatment (acquired): Oral: Acute induction: 10-25 mg once daily (in combination with pyrimethamine [with either sulfadiazine, clindamycin, or atovaquone]) for ≥6 weeks

Adolescents: Refer to adult dosing

Due to calcium content, do not administer IV solutions at a rate >160 mg/minute; not intended for intrathecal use.

Refer to individual protocols. Should be administered IM, IV push, or IV infusion (15 minutes to 2 hours). Leucovorin should not be administered concurrently with methotrexate. It is commonly initiated 24 hours after the start of methotrexate. Toxicity to normal tissues may be irreversible if leucovorin is not initiated by ~40 hours after the start of methotrexate.

As a rescue after folate antagonists: Administer by IV bolus, IM, or orally.

Do not administer orally in the presence of nausea or vomiting. Doses >25 mg should not be administered orally (should be converted to parenteral therapy).

Combination therapy with fluorouracil: Fluorouracil is usually given after, or at the midpoint, of the leucovorin infusion. Leucovorin is usually administered by IV bolus injection or short (10 to 120 minutes) IV infusion. Other administration schedules have been used; refer to individual protocols.

For the treatment of methanol toxicity, infuse over 30 to 60 minutes (Barceloux, 2002)

Frequency not defined. Toxicities (especially gastrointestinal toxicity) of fluorouracil are enhanced when used in combination with leucovorin.

Dermatologic: Erythema, pruritus, skin rash, urticaria

Hematologic & oncologic: Thrombocythemia

Hypersensitivity: Anaphylactoid reaction, hypersensitivity reaction

Respiratory: Wheezing

Animal reproduction studies have not been conducted. Leucovorin is a biologically active form of folic acid. Adequate amounts of folic acid are recommended during pregnancy. Refer to Folic Acid monograph.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber seizures, severe dizziness, or passing out (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.