What is the purpose of leucovorin?
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Leucovorin is not a chemotherapy drug. However, it is often given as part of chemotherapy. Leucovorin is administered to make the treatment more effective or to reduce side effects. Show
This information deals with leucovorin when administered alongside drugs such as fluorouracil (5-FU) or methotrexate. Leucovorin is common given with 5-FU to treat cancers of the colon, rectum, and other parts of the digestive system. It has been proven that adding leucovorin increases the effectiveness of 5-FU. Leucovorin can also be given with the chemotherapy drug tegaful-uracil, which is similar to 5-FU. Leucovorin is commonly given with methotrexate, which is used to treat many different types of cancer. It is mostly given with high doses of methotrexate and can help reduce side effects. This is sometimes referred to as "folinic acid rescue" or "leucovorin rescue." HOW IS LEUCOVORIN ADMINISTERED? Leucovorin is given in the chemotherapy day unit or during a hospital stay. A chemotherapy nurse will give it to you. You will also be able to see a doctor or nurse before having chemotherapy. Chemotherapy drugs may be given in the following ways:
Leucovorin can also be given in tablet form. Before you leave the hospital, your nurse or pharmacist will give you the tablets to take home with you. It is important to take the tablets exactly as explained to you. OTHER INFORMATION ON LEUCOVORIN OTHER DRUGS Some medicines can interact with leucovorin or be harmful if they are taken alongside leucovorin. This includes medications that can be purchased in a store or pharmacy. Tell your doctor if you are taking any medicines, including over-the-counter drugs, complementary therapies, and herbal remedies. 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
High Dose Methotrexate Rescue10 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
Delayed late methotrexate elimination
Delayed early methotrexate elimination and/or evidence of acute renal injury
Dosing considerations
Megaloblastic Anemia Due to Folate DeficiencyUp 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 Poisoning1 mg/kg (50-70 mg adults) IV q4-6hr Trimethoprim Toxicity10 mg/m² PO q6hr Other Indications & UsesBone marrow suppression due to folic acid antagonism Dosage Forms & Strengthstablets
injection, powder for reconstitution
injectable solution
Methotrexate OverdoseAdminister 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
High Dose Methotrexate Rescue10 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
Delayed late methotrexate elimination
Delayed early methotrexate elimination and/or evidence of acute renal injury
Dosing considerations
Megaloblastic Anemia Due to Folate DeficiencyUp 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 Toxicity10 mg/m² PO q6hr Next: InteractionsInteraction CheckerEnter a drug nameand leucovorin No Results
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Previous Next: Adverse EffectsFrequency Not DefinedDiarrhea Nausea Vomiting Stomatitis Thrombocytosis Anaphylactoid reaction Wheezing Urticaria Anaphylactoid reactions Previous Next: WarningsContraindicationsVitamin B12 deficiency anemia and pernicious anemia CautionsHypersensitivity 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 Previous Next: Pregnancy & LactationPregnancy Category: C Lactation: not known whether distributed in breast milk; use caution Pregnancy CategoriesA: 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.Previous Next: PharmacologyMechanism of ActionServes 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 PharmacokineticsDistribution: 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) Previous Next: AdministrationIV IncompatibilitiesAdditive: fluorouracil, trimetrexate Syringe: droperidol, trimetrexate, fluorouracil Y-site: amphotericin B cholesteryl sulfate, droperidol, foscarnet, NaHCO3 IV CompatibilitiesSolution: 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 PreparationReconstitute 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 AdministrationInfusion: not to exceed 160 mg/min Previous Next: ImagesBRANDFORM.UNIT PRICEPILL IMAGEleucovorin calcium injection - 50 mg vial- 100 mg vial- 200 mg vial- 350 mg vial- 350 mg vial- 100 mg vial- 200 mg vial- 500 mg vial- 200 mg vial- 500 mg vial- 350 mg vial- 200 mg vial- 100 mg vial- 50 mg vial- 5 mg tablet- 25 mg tablet- 15 mg tablet- 10 mg tablet- 5 mg tablet- 5 mg tablet- 25 mg tablet- 15 mg tablet- 10 mg tablet- 25 mg tablet- 15 mg tablet- 10 mg tablet- 5 mg tabletCopyright © 2010 First DataBank, Inc. Previous Next: Patient HandoutSelect a drug: Patient Education 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 as directed by your doctor, usually every 6 hours or once daily.The dosage is based on your medical condition and response to treatment.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, get medical help right away 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 away from light and moisture. Do not store in the bathroom. Keep all medications 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. Information last revised September 2022. Copyright(c) 2022 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. Previous Next: FormularyFormularyPatient Discounts Adding plans allows you to compare formulary status to other drugs in the same class. To view formulary information first create a list of plans. Your list will be saved and can be edited at any time. Create Your List of Plans Adding plans allows you to:
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. View explanations for tiers and restrictions TierDescription1This drug is available at the lowest co-pay. Most commonly, these are generic drugs.2This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.3This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.4This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.5This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.6This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.NCNOT COVERED – Drugs that are not covered by the plan.CodeDefinitionPAPrior Authorization Plans Select State: Done Non-Medicare Plans Medicare Plans Done CLOSE Additional Offers CLOSE Email to Patient From: To: The recipient will receive more details and instructions to access this offer. By clicking send, you acknowledge that you have permission to email the recipient with this information. Send CLOSE Email Forms to Patient From: To: The recipient will receive more details and instructions to access this offer. By clicking send, you acknowledge that you have permission to email the recipient with this information. Send Previous Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature. What is the leucovorin used for?Leucovorin is used as an antidote to the harmful effects of methotrexate (a cancer medicine) that is given in high doses. It is used also to prevent or treat certain kinds of anemia. Leucovorin acts the same way in the body as folic acid, which may be low in these patients.
What is the mechanism of action of leucovorin?MECHANISM OF ACTION:
Leucovorin is folic acid in its active (reduced) form, so it allows nucleic acid synthesis to proceed even in the presence of methotrexate. Leucovorin can also compete with methotrexate for the same transport processes into the cell.
What happens if you don't take leucovorin?Severe immunosuppression and toxicity can occur if doses are missed or not given on time.
Is leucovorin always given with methotrexate?Leucovorin is also given with a chemotherapy agent called methotrexate, but in this case it is given to "rescue" normal, healthy cells from the damage caused by the methotrexate. In order to give the methotrexate time to kill the cancer cells, leucovorin is started 12-24 hours after the methotrexate is given.
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