leucovorin (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablets

  • 5mg
  • 10mg
  • 15mg
  • 25mg

injection, powder for reconstitution

  • 50mg
  • 100mg
  • 200mg
  • 350mg
  • 500mg

injectable solution

  • 10mg/mL

Methotrexate Overdose

Administer as soon as possible and within 24 hr methotrexate level is >10-6 M or 48 hour level is >9 x 10-7 M, the dose of leucovorin should be increased to 100 mg/m2 IV every 3 hours until methotrexate level is <10-8 M

Dosing considerations

  • Hydration (3 L/day) and urinary alkalinization with sodium bicarbonate solution should be employed concomitantly; bicarbonate dose should be adjusted to maintain urine pH at 7.0 or greater

High Dose Methotrexate Rescue

10 mg/m² IV q6hr for 10 doses; starts 24 hours after beginning of methotrexate infusion  

May give PO after 1st IV dose

Adjust dose as follows:

Normal methotrexate elimination

  • Serum methotrexate level approximately 10 micromolar, 24 hr after administration, 1 micromolar at 48 hr, <0.2 micromolar at 72 hr
    • Administer 15 mg PO, IM, or IV q6hr for 60 hr (10 doses starting at 24 hr after start of methotrexate infusion

Delayed late methotrexate elimination

  • Serum methotrexate level remaining above 0.2 micromolar at 72 hr, and more than 0.05 micromolar at 96 hr after administration
    • Continue 15 mg PO, IM, or IV q6hr, until methotrexate level <0.05 micromolar

Delayed early methotrexate elimination and/or evidence of acute renal injury

  • Serum methotrexate level of 50 micromolar or more at 24 hr, or 5 micromolar or more at 48 hr after administration, or a 100% or greater increase in serum creatinine level at 24 hr after methotrexate administration (eg, increase from 0.5 mg/dL to a level of 1 mg/dL or more)
    • Administer 150 mg IV q3hr until methotrexate level is <1 micromolar; then 15 mg IV q3hr until methotrexate level is <0.05 micromolar

Dosing considerations

  • In presence of gastrointestinal toxicity, nausea or vomiting, administer leucovorin parenterally; do not administer leucovorin intrathecally; serum creatinine and methotrexate levels should be determined at least once daily
  • Administration, hydration, and urinary alkalization (pH of 7.0 or greater) should be continued until methotrexate level is below 5 x 10-8 M (0.05 micromolar)

Megaloblastic Anemia Due to Folate Deficiency

Up to 1 mg daily; there is no evidence that doses >1 mg/day have greater efficacy than those of 1 mg; additionally, loss of folate in urine becomes roughly logarithmic as the amount administered exceeds 1 mg

Coadministration with Trimetrexate (Discontinued)

20 mg/m² IV/PO q6hr (for PO, round dose up to next 25 mg increment)  

Dose adjustment for both trimetrexate & leucovorin may be necessary if hematologic toxicity occurs

Advanced Colorectal Carcinoma (with 5FU)

Recommended 20 mg/m² IV followed by 425 mg/m² fluorouracil  

Dose reduction treatment pause may be necessary based on hematologic toxicity

Methanol Poisoning

1 mg/kg (50-70 mg adults) IV q4-6hr

Trimethoprim Toxicity

10 mg/m² PO q6hr

Other Indications & Uses

Bone marrow suppression due to folic acid antagonism

Dosage Forms & Strengths

tablets

  • 5mg
  • 10mg
  • 15mg
  • 25mg

injection, powder for reconstitution

  • 50mg
  • 100mg
  • 200mg
  • 350mg
  • 500mg

injectable solution

  • 10mg/mL

Methotrexate Overdose

Administer as soon as possible and within 24 hr methotrexate level is >10-6 M or 48 hour level is >9 x 10-7 M, the dose of leucovorin should be increased to 100 mg/m2 IV every 3 hours until methotrexate level is <10-8 M

Dosing considerations

  • Hydration (3 L/day) and urinary alkalinization with sodium bicarbonate solution should be employed concomitantly; bicarbonate dose should be adjusted to maintain urine pH at 7.0 or greater

High Dose Methotrexate Rescue

10 mg/m² IV q6hr for 10 doses; starts 24 hr after beginning of methotrexate infusion

May give PO after 1st IV dose

Adjust dose as follows:

Normal methotrexate elimination

  • Serum methotrexate level approximately 10 micromolar, 24 hr after administration, 1 micromolar at 48 hr, <0.2 micromolar at 72 hr
    • Administer 15 mg PO, IM, or IV q6hr for 60 hr (10 doses starting at 24 hr after start of methotrexate infusion

Delayed late methotrexate elimination

  • Serum methotrexate level remaining above 0.2 micromolar at 72 hr, and more than 0.05 micromolar at 96 hr after administration
    • Continue 15 mg PO, IM, or IV q6hr, until methotrexate level <0.05 micromolar

Delayed early methotrexate elimination and/or evidence of acute renal injury

  • Serum methotrexate level of 50 micromolar or more at 24 hr, or 5 micromolar or more at 48 hr after administration, or a 100% or greater increase in serum creatinine level at 24 hr after methotrexate administration (eg, increase from 0.5 mg/dL to a level of 1 mg/dL or more)
    • Administer 150 mg IV q3hr until methotrexate level is <1 micromolar; then 15 mg IV q3hr until methotrexate level is <0.05 micromolar

Dosing considerations

  • In presence of gastrointestinal toxicity, nausea or vomiting, leucovorin should be administered parenterally; do not administer leucovorin intrathecally; serum creatinine and methotrexate levels should be determined at least once daily
  • Administration, hydration, and urinary alkalization (pH of 7.0 or greater) should be continued until methotrexate level is below 5 x 10-8 M (0.05 micromolar)

Megaloblastic Anemia Due to Folate Deficiency

Up to 1 mg daily; there is no evidence that doses > 1 mg/day have greater efficacy than those of 1 mg; additionally, loss of folate in urine becomes roughly logarithmic as the amount administered exceeds 1 mg

Trimethoprim Toxicity

10 mg/m² PO q6hr

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Interactions

Interaction Checker

and leucovorin

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              Serious - Use Alternative (1)

              • trimethoprim

                leucovorin decreases effects of trimethoprim by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Monitor for trimethoprim treatment failure or decreased efficacy when coadministered with leucovorin, especially when used with sulfamethoxazole for Pneumocystis jiroveci pneumonia in patients who are HIV positive .

              Monitor Closely (3)

              • capecitabine

                leucovorin increases effects of capecitabine by pharmacodynamic synergism. Use Caution/Monitor.

              • fluorouracil

                leucovorin increases toxicity of fluorouracil by pharmacodynamic synergism. Use Caution/Monitor.

              • glucarpidase

                glucarpidase will decrease the level or effect of leucovorin by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)

              Minor (0)

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                Adverse Effects

                Frequency Not Defined

                Diarrhea

                Nausea

                Vomiting

                Stomatitis

                Thrombocytosis

                Anaphylactoid reaction

                Wheezing

                Urticaria

                Anaphylactoid reactions

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                Warnings

                Contraindications

                Vitamin B12 deficiency anemia and pernicious anemia

                Cautions

                Hypersensitivity reactions including anaphylactoid reactions & urticaria

                Risk of severe neurological complications in patients with undiagnosed anemia

                Geriatric or debilitated patients receiving cotreatment with fluorouracil

                May increase treatment failure of sulfamethoxazole-trimethoprim therapies

                Formulations containing benzyl alcohol not to be used in infants

                Thrombocytosis reported during intra-arterial infusion of methotrexate

                In treatment of accidental overdosages of folic acid antagonists, IV leucovorin should be administered as promptly as pos­sible; as the time interval between antifolate administration (eg, methotrexate) and leucovorin rescue increases, leucovorin’s effective­ness in counteracting toxicity decreases

                In the treatment of accidental overdosages of intrathecally administered folic acid antagonists, do not administer leucovorin intrathecally (may be fatal)

                Monitoring of serum methotrexate concentration is essential in determining optimal dose and duration of treatment with leucovorin; delayed methotrexate excretion may be caused by a third space fluid accumulation (ie, ascites, pleural effusion), renal insufficiency, or inadequate hydration; under such circumstances, higher doses of leucovorin or prolonged administration may be indicated

                Doses higher than those recommended for oral use must be given IV; because of the benzyl alcohol contained in certain diluents used for reconstituting drug for Injection, when doses > 10 mg/m2 administered, reconstitute leucovorin calcium for Injection with sterile water for Injection, USP, and used immediately

                Because of calcium content of leucovorin solution, no more than 160 mg of leucovorin should be injected intravenously per minute (16 mL of a 10 mg/mL, or 8 mL of a 20 mg/mL solution per minute)

                Leucovorin enhances toxicity of 5-fluorouracil; when these drugs are administered concurrently in the palliative therapy of advanced colorectal cancer, the dosage of 5-fluorouracil must be lower than usually administered

                Although toxicities observed in patients treated with combination of leucovorin plus 5-fluorouracil are qualitatively similar to those observed in patients treated with 5-fl uoro­uracil alone, gastrointestinal toxicities (particularly stomatitis and diarrhea) are observed more commonly and may be more severe and of prolonged duration in patients treated with the combination

                Therapy with leucovorin and 5-fluorouracil must not be initiated or continued in patients who have symptoms of gastrointestinal toxicity of any severity until those symptoms have completely resolved

                Patients with diarrhea must be monitored with particular care until diarrhea has resolved, as rapid clinical deterioration leading to death can occur; in an additional study utilizing higher weekly doses of 5-fluorouracil and leucovorin, elderly and/or debilitated patients were found to be at greater risk for severe gastrointestinal toxicity

                Seizures and/or syncope reported rarely in cancer patients receiving leucovorin, usually in association with fluoropyrimidine administration, and most commonly in those with CNS metastases or other predisposing factors, however, a causal relationship has not been established

                Parenteral administration is preferable to oral dosing if there is possibility that patient may vomit and not absorb the leucovorin; leucovorin has no effect on non-hematologic toxicities of methotrexate such as nephrotoxicity resulting from drug and/ or metabolite precipitation in the kidney

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                Pregnancy & Lactation

                Pregnancy Category: C

                Lactation: not known whether distributed in breast milk; use caution

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Serves as a cofactor supplement to counteract folic acid antagonists such as methotrexate; leucovorin is an active metabolite of folic acid

                Displaces methotrexate from intracellular binding sites and restores the folate required for DNA/RNA synthesis

                In methanol toxicity it serves as a tetrahydrofolate source to help the body eliminate the formic acid resulting from methanol's toxicity

                Pharmacokinetics

                Distribution: all body tissues, predominantly in liver

                Metabolism: Rapidly converted to THF derivatives

                Excretion: Urine (primarily); feces

                Half-life elimination: 4-8hr

                Peak plasma time: 2 hr (PO); 10 min (as folate); 1 hr (as tetrahydrofolate)

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                Administration

                IV Incompatibilities

                Additive: fluorouracil, trimetrexate

                Syringe: droperidol, trimetrexate, fluorouracil

                Y-site: amphotericin B cholesteryl sulfate, droperidol, foscarnet, NaHCO3

                IV Compatibilities

                Solution: compatible w/ most common fluids

                Additive: cisplatin, cisplatin w/ floxuridine, floxuridine

                Syringe: bleomycin, cisplatin, cyclophosphamide, doxorubicin, droperidol, fluorouracil, furosemide, heparin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine

                Y-site (partial list): bleomycin, cisplatin, cyclophosphamide, fluorouracil(?), furosemide, heparin, linezolid, methotrexate, metoclopramide, mitomycin

                IV Preparation

                Reconstitute w/ BWI or SWI of 10 mg/mL or 20 mg/mL (for 350 mg vial)

                Available in 10 mg/mL preservative-free solutions

                Do not use benzyl alcohol-containing diluents for doses >10 mg/sq.meter

                Reconstituted solution is stable for 7 d

                Use immediately if reconstituted w/ preservative-free solution

                IV/IM Administration

                Infusion: not to exceed 160 mg/min

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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                leucovorin calcium oral
                -
                5 mg tablet
                leucovorin calcium oral
                -
                25 mg tablet
                leucovorin calcium oral
                -
                10 mg tablet
                leucovorin calcium oral
                -
                15 mg tablet
                leucovorin calcium oral
                -
                5 mg tablet
                leucovorin calcium oral
                -
                25 mg tablet
                leucovorin calcium injection
                -
                100 mg vial
                leucovorin calcium injection
                -
                350 mg vial
                leucovorin calcium injection
                -
                200 mg vial
                leucovorin calcium injection
                -
                500 mg vial
                leucovorin calcium injection
                -
                200 mg vial
                leucovorin calcium injection
                -
                200 mg vial
                leucovorin calcium injection
                -
                350 mg vial
                leucovorin calcium injection
                -
                50 mg vial
                leucovorin calcium injection
                -
                100 mg vial
                leucovorin calcium injection
                -
                500 mg vial
                leucovorin calcium injection
                -
                350 mg vial
                leucovorin calcium injection
                -
                200 mg vial
                leucovorin calcium injection
                -
                100 mg vial
                leucovorin calcium injection
                -
                50 mg vial

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

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                Patient Education
                leucovorin calcium oral

                LEUCOVORIN - ORAL

                (lew-ko-VORE-in)

                USES: This medication is used to treat or prevent serious blood cell disorders (such as thrombocytopenia, neutropenia, anemia) caused by certain drugs (folic acid antagonists such as methotrexate, trimethoprim, pyrimethamine).

                HOW TO USE: Take this medication by mouth with or without food, usually every 6 hours or once daily or as directed by your doctor.Dosage is based on your medical condition and response to treatment. Doses above 25 milligrams are not recommended.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.Tell your doctor if you are unable to take this medication because of nausea/vomiting. You may need to be switched to the injection form of this medication.

                SIDE EFFECTS: Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Before taking leucovorin, tell your doctor or pharmacist if you are allergic to it; or to levoleucovorin; or to folic acid or folinic acid; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain anemias (due to vitamin B12 deficiency).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Leucovorin is very similar to levoleucovorin. Do not use medications containing levoleucovorin while using leucovorin.

                OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as kidney function, complete blood count, folic acid antagonist blood levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

                MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

                STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

                Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

                FormularyPatient Discounts

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                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
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                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.