Leucovorin – Uses, Dosage, Side Effects, Interaction

Last updated: February 8, 2026Reviewed date: February 8, 2026Reading time: 26 min read
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Leucovorin - Uses, Dosage, Side Effects, Interaction
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Leucovorin is a derivative of folic acid with chemoprotection, antidote, and synergistic activity. Leucovorin does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonist-type chemotherapeutic drugs, and is converted to a tetrahydrofolate, which is the necessary folate for purine and pyrimidine synthesis....

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Article Summary

Leucovorin is a derivative of folic acid with chemoprotection, antidote, and synergistic activity. Leucovorin does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonist-type chemotherapeutic drugs, and is converted to a tetrahydrofolate, which is the necessary folate for purine and pyrimidine synthesis. As this agent allows for some purine/pyrimidine synthesis to occur, the toxic effects of folic acid antagonist-type chemotherapeutic drugs are...

Key Takeaways

  • This article explains Mechanism of Action in simple medical language.
  • This article explains Indications in simple medical language.
  • This article explains Contraindications in simple medical language.
  • This article explains Dosage in simple medical language.
Educational health guideWritten for patient understanding and clinical awareness.
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  • Any symptom that feels urgent, unusual, or unsafe for the patient.
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Definition

Leucovorin is a derivative of folic acid with chemoprotection, antidote, and synergistic activity. Leucovorin does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonist-type chemotherapeutic drugs, and is converted to a tetrahydrofolate, which is the necessary folate for purine and pyrimidine synthesis. As this agent allows for some purine/pyrimidine synthesis to occur, the toxic effects of folic acid antagonist-type chemotherapeutic drugs are counteracted while still permitting the antitumor activity of the folic acid antagonist through dihydrofolate reductase inhibition. This agent also potentiates the effects of 5-fluorouracil and its derivatives by stabilizing the binding of 5-fluorouracil’s converted form fluorodeoxyuridylic acid to its target enzyme thymidylate synthase, thus prolonging drug activity.

Folinic Acid (also known as 5-formyl tetrahydrofolic acid or leucovorin) is the 5-formyl derivative of tetrahydrofolic acid, a necessary co-factor in the body. Commercially available leucovorin is composed of a 1:1 racemic mixture of the dextrorotary and levorotary isomers, while levoleucovorin contains only the pharmacologically active levo-isomer. In vitro, the levo-isomer has been shown to be rapidly converted to the biologically available methyl-tetrahydrofolate form while the dextro form is slowly excreted by the kidneys. Despite this difference in activity, the two commercially available forms have been shown to be pharmacokinetically identical and may be used interchangeably with limited differences in efficacy or side effects (Kovoor et al, 2009). As folate analogs, leucovorin and levoleucovorin are both used to counteract the toxic effects of folic acid antagonists, such as methotrexate, which act by inhibiting the enzyme dihydrofolate reductase (DHFR). They are indicated for use as rescue therapy following use of high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Injectable forms are also indicated for use in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible and for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Folic acid is an essential B vitamin required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. However, in order to function in this role, it must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted when high-dose methotrexate is used for cancer therapy. As methotrexate functions as a DHFR inhibitor to prevent DNA synthesis in rapidly dividing cells, it also prevents the formation of DHF and THF. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects associated with methotrexate therapy. As levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF), they are able to bypass DHFR reduction and act as a cellular replacement for the co-factor THF, thereby preventing these toxic side effects.

Mechanism of Action

As leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.

Leucovorin is a derivative of tetrahydrofolic acid, the reduced form of folic acid, which is involved as a cofactor for 1-carbon transfer reactions in the biosynthesis of purines and pyrimidines of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective DNA synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Because of its ready conversion to other tetrahydrofolic acid derivatives, leucovorin is a potent antidote for both the hematopoietic and reticuloendothelial toxic effects of folic acid antagonists (eg, methotrexate, pyrimethamine, trimethoprim). It is postulated that in some cancers leucovorin enters and rescues normal cells from the toxic effects of folic acid antagonists, in preference to tumor cells, because of a difference in membrane transport mechanisms; this principle is the basis of high dose methotrexate therapy with leucovorin rescue.

Leucovorin is one of several active, chemically reduced derivatives of folic acid. It is useful as an antidote to drugs which act as folic acid antagonists. Leucovorin is a mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid (THF). The biologically active compound of the mixture is the (-)-l-isomer, known as Citrovorum factor or (-)-folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase. Leucovorin has also been used to enhance the activity of fluorouracil.

Indications

  • For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
  • Leucovorin is indicated for use in combination with agents such as fluorouracil or high-dose methotrexate, as second-line treatment of squamous cell head and neck carcinoma.
  • Leucovorin is indicated as a antidote to the toxic effects of folic acid antagonists such as methotrexate, pyrimethamine, or trimethoprim. Leucovorin also is indicated as a rescue after high-dose methotrexate therapy in osteosarcoma and as a part of chemotherapeutic treatment programs in the management of several forms of cancer.
  • Leucovorin is indicated to treat megaloblastic anemias associated with sprue, nutritional deficiency, pregnancy, and infancy when oral folic acid therapy is not feasible. Leucovorin is not recommended for use in the treatment of pernicious anemia or other megaloblastic anemias secondary to lack of vitamin B12, since it may produce a hematologic remission while neurologic manifestations continue to progress.
  • For use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer
  • Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages.
  • Advanced Colorectal Cancer
  • Advanced Esophageal Cancers
  • Advanced Gastric Cancer
  • Anemia of Pregnancy
  • Bladder Cancer, Cancer
  • Folate and iron deficiency
  • Folate deficiency
  • Folic acid antagonist overdose
  • Iron Deficiency (ID)
  • Macrocytic anemia
  • Megaloblastic anemia
  • Pancreatic Metastatic Cancer
  • Postpartum Anemia
  • Hypochromic anemia
  • Methotrexate toxicity
  • Normochromic anemia
  • Pyrimethamine hematologic toxicity

Use in Cancer

Leucovorin calcium is approved to be used alone or with other drugs to treat:

  • Colorectal cancer. It is used with fluorouracil as a palliative treatment in patients with advanced disease.
  • Anemia. It is used to treat megaloblastic anemia which occurs when the body does not get enough of a vitamin called folic acid. It is used by patients who cannot take the vitamin by mouth.

Leucovorin calcium is also used to prevent and treat the toxic effects of high-dose methotrexate when used to treat osteosarcoma and other types of cancer. It is also used to treat overdoses of methotrexate or other folic acid antagonists. The drug is also being studied in the treatment of other conditions and types of cancer.

Contraindications

  • If the clinician is using leucovorin alone to treat megaloblastic anemia, they must rule out B12 deficiency. Treating vitamin B12 deficient patients with leucovorin may reverse the megaloblastic anemia; however, it will worsen the neurological manifestations of B12 deficiency.
  • inadequate vitamin B12
  • anemia due to vitamin B12 deficiency-pernicious anemia

Dosage

Strengths: 15 mg; 5 mg; 10 mg; 25 mg; 10 mg/mL; 100 mg; 200 mg; 350 mg; 50 mg; 500 mg

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
  • 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.

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
  • 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.

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
  • 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.

Megaloblastic Anemia

  • Up to 1 mg, IV or IM, once a day
  • 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.
  • Treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible

Folic Acid Antagonist Overdose

  • 5 to 15 mg orally once a day
  •  Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists.

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
  • Use in combination with trimetrexate.
  • Treatment of pneumocystis pneumonia in HIV infected patients

Pneumocystis Pneumonia Prophylaxis

  • Prophylaxis of pneumocystis pneumonia is not a labeled indication.
  • 25 mg, orally, once a week, in combination with dapsone and pyrimethamine
  • 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.
  • Pneumocystis pneumonia prophylaxis in immunocompromised patients

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

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
  • 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.

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
  • 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.

Pediatric Dose for Megaloblastic Anemia

  • Up to 1 mg, IV or IM, once a day
  • 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.

Pediatric Dose for Folic Acid Antagonist Overdose

  • 5 to 15 mg orally once a day
  • Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists.

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.

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.

Side Effects

The Most Common

  • Stomatitis (75%, when used with fluorouracil), nausea (74%, when used with fluorouracil), diarrhea (66%, when used with fluorouracil), vomiting (46%, when used with fluorouracil), dehydration (when used with fluorouracil)
  • Constipation (when used with fluorouracil)
  • Gastrointestinal disorders (after high doses)
  • diarrhea
  • rash
  • hives
  • itching
  • difficulty breathing or swallowing

More Common

  • Mucositis (when used with fluorouracil), cheilitis (when used with fluorouracil)
  • Leucopenia (69%, when used with fluorouracil)
  • Thrombocytopenia (when used with fluorouracil)
  • Allergic reactions (sensitization, including anaphylactoid reactions, shock, and urticaria)
  • Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (in combination with other agents)
  • Alopecia (42%, when used with fluorouracil), dermatitis (21%, when used with fluorouracil)
  • Palmar-plantar erythrodysesthesia (when used with fluorouracil)
  • Lethargy/malaise/fatigue (13%, when used with fluorouracil)
  • Pyrexial reactions (following parenteral administration)[rx]

Rare

  • Skin rash, hives, or itching
  • wheezing
  • Convulsions (seizures)
  • Anorexia (14%, when used with fluorouracil)
  • Hyperammonemia (when used with fluorouracil)
  • Infection (when used with fluorouracil)
  • Increase in the frequency of attacks in epileptics, seizures, syncope
  •  Insomnia, agitation, depression

Drug Interactions

Pregnancy and Lactation

FDA Pregnancy Category C

Pregnancy

Animal reproduction studies have not been conducted with leucovorin. It is also not known whether leucovorin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Leucovorin should be given to a pregnant woman only if clearly needed.

Lactation

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human
milk, caution should be exercised when leucovorin is administered to a nursing mother.

How should this medicine be used?

Leucovorin comes as a tablet to take by mouth. It is usually taken every 6 hours until laboratory tests show it is no longer needed. Sometimes leucovorin is taken on a different schedule, depending on the reason it is needed. Take leucovorin at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take leucovorin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

What special precautions should I follow?

Before taking leucovorin,

  • tell your doctor and pharmacist if you are allergic to leucovorin, levoleucovorin, folic acid (Folicet, in multivitamins), any other medications, or any of the ingredients in leucovorin tablets. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain medications for seizures such as phenobarbital, phenytoin (Dilantin), and primidone (Mysoline); and trimethoprim-sulfamethoxazole (Bactrim, Septra). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have anemia (low number of red blood cells) caused by lack of vitamin B12 or inability to absorb vitamin B12. Your doctor will not prescribe leucovorin to treat this type of anemia.
  • tell your doctor if you have or have ever had a buildup of fluid in the chest cavity or the stomach area or kidney disease. Also tell your doctor if you are nauseated.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking leucovorin, call your doctor.

References

Doctor visit helper

Prepare before seeing a doctor

A simple rural-patient checklist to help you explain symptoms clearly, ask better questions, and avoid unsafe self-treatment.

Safety note: This is not a prescription or diagnosis. For severe symptoms, pregnancy danger signs, children with serious illness, chest pain, breathing difficulty, stroke-like weakness, or major injury, seek urgent care.

Which doctor may help?

Start with a registered doctor or the nearest qualified health center.

What to tell the doctor

  • Write when the problem started and how it changed.
  • Bring old prescriptions, investigation reports, and current medicines.
  • Write allergies, pregnancy status, diabetes, kidney/liver disease, and major past illnesses.
  • Bring one family member if the patient is weak, elderly, confused, or a child.

Questions to ask

  • What is the most likely cause of my symptoms?
  • Which danger signs mean I should go to hospital quickly?
  • Which tests are necessary now, and which can wait?
  • How should I take medicines safely and what side effects should I watch for?
  • When should I come for follow-up?

Tests to discuss

  • Vital signs: temperature, pulse, blood pressure, oxygen saturation
  • Basic physical examination by a clinician
  • CBC, urine test, blood sugar, or imaging only when clinically needed

Avoid these mistakes

  • Do not use antibiotics, steroid tablets/injections, or strong painkillers without proper medical advice.
  • Do not hide pregnancy, kidney disease, ulcer, allergy, or blood thinner use.
  • Do not delay emergency care when danger signs are present.

Medicine safety and first-aid guide

This section is for patient education only. It does not replace a doctor, pharmacist, or emergency care.

Safe first steps

  • Avoid heavy lifting, sudden bending, and prolonged bed rest.
  • Use comfortable posture and gentle movement as tolerated.
  • Discuss physiotherapy, X-ray, or MRI only when clinically needed.

OTC medicine safety

  • For mild back pain, pain-relief medicine may be discussed with a doctor or pharmacist.
  • Avoid repeated painkiller use if you have kidney disease, stomach ulcer, uncontrolled blood pressure, or are taking blood thinners.

Avoid these mistakes

  • Do not start antibiotics without a proper medical decision.
  • Do not use steroid tablets or injections casually for quick relief.
  • Do not delay emergency care because of home remedies.

Get urgent help if

  • Back pain with leg weakness, numbness around private area, loss of urine/stool control, fever, cancer history, or major injury needs urgent care.
Medicine names, dose, and timing must be decided by a qualified clinician or pharmacist after checking age, pregnancy, allergy, other diseases, and current medicines.

For rural patients and family caregivers

Patient health record and symptom diary

Write your symptoms, medicines already taken, test results, and questions before visiting a doctor. This note stays on your device unless you print or copy it.

Doctor to discuss: Doctor / qualified healthcare provider
Tests to discuss with doctor
  • Basic vital signs: temperature, pulse, blood pressure, oxygen level if needed
  • Relevant blood, urine, imaging, or specialist tests only after clinical assessment
Questions to ask
  • What is the most likely cause of my symptoms?
  • Which warning signs mean I should go to emergency care?
  • Which tests are really needed now?
  • Which medicines are safe for my age, pregnancy status, allergy, kidney/liver/stomach condition, and current medicines?

Emergency warning signs such as chest pain, severe breathing difficulty, sudden weakness, confusion, severe dehydration, major injury, or loss of bladder/bowel control need urgent medical care. Do not wait for online information.

Safe pathway to proper treatment

Care roadmap for: Leucovorin – Uses, Dosage, Side Effects, Interaction

Use this simple roadmap to understand the next safe steps. It is educational and does not replace examination by a doctor.

Go to emergency care if you notice:
  • Severe or rapidly worsening symptoms
  • Breathing difficulty, chest pain, fainting, confusion, severe weakness, major injury, or severe dehydration
Doctor / service to discuss: Qualified healthcare provider; specialist depends on symptoms and examination.
  1. Step 1

    Check danger signs first

    If danger signs are present, seek emergency care and do not wait for online information.

  2. Step 2

    Record the symptom story

    Write when symptoms started, severity, medicines already taken, allergies, pregnancy status, and test results.

  3. Step 3

    Visit a qualified clinician

    A doctor, nurse, or qualified healthcare provider can examine you and decide which tests or treatment are needed.

  4. Step 4

    Do only useful tests

    Do tests after clinical assessment. Avoid unnecessary tests, random antibiotics, or repeated medicines without diagnosis.

  5. Step 5

    Follow up and return early if worse

    If symptoms worsen, new warning signs appear, or treatment is not helping, return for review quickly.

Rural patient practical tips
  • Take a written symptom diary and all previous prescriptions/test reports.
  • Do not hide medicines already taken, even herbal or over-the-counter medicines.
  • Ask which warning signs mean urgent referral to hospital.

This roadmap is for education. A real diagnosis and treatment plan requires history, examination, and clinical judgment.

RX Patient Help

Ask a health question safely

Write your symptom story. A health professional or site editor can review it before any answer is prepared. This box is not for emergency care.

Emergency first: Severe chest pain, breathing trouble, unconsciousness, stroke signs, severe injury, heavy bleeding, or rapidly worsening symptoms need urgent local medical care now.

Frequently Asked Questions

Mechanism of Action As leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase. Leucovorin is a derivative of tetrahydrofolic acid, the reduced form of folic acid, which is involved as a cofactor for 1-carbon transfer reactions in the biosynthesis of purines and pyrimidines of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective DNA synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Because of its ready conversion to other tetrahydrofolic acid derivatives, leucovorin is a potent antidote for both the hematopoietic and reticuloendothelial toxic effects of folic acid antagonists (eg, methotrexate, pyrimethamine, trimethoprim). It is postulated that in some cancers leucovorin enters and rescues normal cells from the toxic effects of folic acid antagonists, in preference to tumor cells, because of a difference in membrane transport mechanisms; this principle is the basis of high dose methotrexate therapy with leucovorin rescue. Leucovorin is one of several active, chemically reduced derivatives of folic acid. It is useful as an antidote to drugs which act as folic acid antagonists. Leucovorin is a mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid (THF). The biologically active compound of the mixture is the (-)-l-isomer, known as Citrovorum factor or (-)-folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase. Leucovorin has also been used to enhance the activity of fluorouracil. Indications For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Leucovorin is indicated for use in combination with agents such as fluorouracil or high-dose methotrexate, as second-line treatment of squamous cell head and neck carcinoma. Leucovorin is indicated as a antidote to the toxic effects of folic acid antagonists such as methotrexate, pyrimethamine, or trimethoprim. Leucovorin also is indicated as a rescue after high-dose methotrexate therapy in osteosarcoma and as a part of chemotherapeutic treatment programs in the management of several forms of cancer. Leucovorin is indicated to treat megaloblastic anemias associated with sprue, nutritional deficiency, pregnancy, and infancy when oral folic acid therapy is not feasible. Leucovorin is not recommended for use in the treatment of pernicious anemia or other megaloblastic anemias secondary to lack of vitamin B12, since it may produce a hematologic remission while neurologic manifestations continue to progress. For use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages. Advanced Colorectal Cancer Advanced Esophageal Cancers Advanced Gastric Cancer Anemia of Pregnancy Bladder Cancer, Cancer Folate and iron deficiency Folate deficiency Folic acid antagonist overdose Iron Deficiency (ID) Macrocytic anemia Megaloblastic anemia Pancreatic Metastatic Cancer Postpartum Anemia Hypochromic anemia Methotrexate toxicity Normochromic anemia Pyrimethamine hematologic toxicity Use in Cancer Leucovorin calcium is approved to be used alone or with other drugs to treat: Colorectal cancer. It is used with fluorouracil as a palliative treatment in patients with advanced disease. Anemia. It is used to treat megaloblastic anemia which occurs when the body does not get enough of a vitamin called folic acid. It is used by patients who cannot take the vitamin by mouth. Leucovorin calcium is also used to prevent and treat the toxic effects of high-dose methotrexate when used to treat osteosarcoma and other types of cancer. It is also used to treat overdoses of methotrexate or other folic acid antagonists. The drug is also being studied in the treatment of other conditions and types of cancer. Contraindications If the clinician is using leucovorin alone to treat megaloblastic anemia, they must rule out B12 deficiency. Treating vitamin B12 deficient patients with leucovorin may reverse the megaloblastic anemia; however, it will worsen the neurological manifestations of B12 deficiency. inadequate vitamin B12 anemia due to vitamin B12 deficiency-pernicious anemia Dosage Strengths: 15 mg; 5 mg; 10 mg; 25 mg; 10 mg/mL; 100 mg; 200 mg; 350 mg; 50 mg; 500 mg 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 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. 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 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. 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 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. Megaloblastic Anemia Up to 1 mg, IV or IM, once a day 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. Treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible Folic Acid Antagonist Overdose 5 to 15 mg orally once a day  Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists. 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 Use in combination with trimetrexate. Treatment of pneumocystis pneumonia in HIV infected patients Pneumocystis Pneumonia Prophylaxis Prophylaxis of pneumocystis pneumonia is not a labeled indication. 25 mg, orally, once a week, in combination with dapsone and pyrimethamine 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. Pneumocystis pneumonia prophylaxis in immunocompromised patients 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 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 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. 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 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. Pediatric Dose for Megaloblastic Anemia Up to 1 mg, IV or IM, once a day 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. Pediatric Dose for Folic Acid Antagonist Overdose 5 to 15 mg orally once a day Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists. 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. 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. Side Effects The Most Common Stomatitis (75%, when used with fluorouracil), nausea (74%, when used with fluorouracil), diarrhea (66%, when used with fluorouracil), vomiting (46%, when used with fluorouracil), dehydration (when used with fluorouracil) Constipation (when used with fluorouracil) Gastrointestinal disorders (after high doses) diarrhea rash hives itching difficulty breathing or swallowing More Common Mucositis (when used with fluorouracil), cheilitis (when used with fluorouracil) Leucopenia (69%, when used with fluorouracil) Thrombocytopenia (when used with fluorouracil) Allergic reactions (sensitization, including anaphylactoid reactions, shock, and urticaria) Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (in combination with other agents) Alopecia (42%, when used with fluorouracil), dermatitis (21%, when used with fluorouracil) Palmar-plantar erythrodysesthesia (when used with fluorouracil) Lethargy/malaise/fatigue (13%, when used with fluorouracil) Pyrexial reactions (following parenteral administration)[rx] Rare Skin rash, hives, or itching wheezing Convulsions (seizures) Anorexia (14%, when used with fluorouracil) Hyperammonemia (when used with fluorouracil) Infection (when used with fluorouracil) Increase in the frequency of attacks in epileptics, seizures, syncope  Insomnia, agitation, depression Drug Interactions Acamprosate The excretion of Acamprosate can be decreased when combined with Leucovorin. Acetylsalicylic acid The excretion of Leucovorin can be decreased when combined with Acetylsalicylic acid. Acyclovir The excretion of Acyclovir can be decreased when combined with Leucovorin. Allopurinol The excretion of Allopurinol can be decreased when combined with Leucovorin. Alprostadil The excretion of Alprostadil can be decreased when combined with Leucovorin. Aminohippuric acid The excretion of Leucovorin can be decreased when combined with Aminohippuric acid. Apalutamide The excretion of Leucovorin can be decreased when combined with Apalutamide. Ataluren The excretion of Leucovorin can be decreased when combined with Ataluren. Avatrombopag The excretion of Leucovorin can be decreased when combined with Avatrombopag. Avibactam The excretion of Avibactam can be decreased when combined with Leucovorin. Baricitinib The serum concentration of Baricitinib can be increased when it is combined with Leucovorin. Benzoic acid The excretion of Leucovorin can be decreased when combined with Benzoic acid. Benzylpenicillin The excretion of Benzylpenicillin can be decreased when combined with Leucovorin. Bumetanide The excretion of Bumetanide can be decreased when combined with Leucovorin. Cabotegravir The excretion of Leucovorin can be decreased when combined with Cabotegravir. Capecitabine The risk or severity of adverse effects can be increased when Leucovorin is combined with Capecitabine. Captopril The excretion of Captopril can be decreased when combined with Leucovorin. Carbamazepine The serum concentration of Leucovorin can be decreased when it is combined with Carbamazepine. Cefaclor The excretion of Cefaclor can be decreased when combined with Leucovorin. Cefadroxil The excretion of Leucovorin can be decreased when combined with Cefadroxil. Cefalotin The excretion of Leucovorin can be decreased when combined with Cefalotin. Cefamandole The excretion of Leucovorin can be decreased when combined with Cefamandole. Cefazolin The excretion of Cefazolin can be decreased when combined with Leucovorin. Cefdinir The excretion of Cefdinir can be decreased when combined with Leucovorin. Cefoperazone The excretion of Leucovorin can be decreased when combined with Cefoperazone. Cefotaxime The excretion of Leucovorin can be decreased when combined with Cefotaxime. Cefotiam The excretion of Leucovorin can be decreased when combined with Cefotiam. Ceftibuten The excretion of Ceftibuten can be decreased when combined with Leucovorin. Ceftizoxime The excretion of Ceftizoxime can be decreased when combined with Leucovorin. Ceftriaxone The excretion of Leucovorin can be decreased when combined with Ceftriaxone. Cephalexin The excretion of Leucovorin can be decreased when combined with Cephalexin. Cholic Acid The excretion of Cholic Acid can be decreased when combined with Leucovorin. Cilastatin The excretion of Leucovorin can be decreased when combined with Cilastatin. Cimetidine The excretion of Leucovorin can be decreased when combined with Cimetidine. Clofarabine The excretion of Clofarabine can be decreased when combined with Leucovorin. Colestipol The serum concentration of Leucovorin can be decreased when it is combined with Colestipol. Conjugated estrogens The excretion of Leucovorin can be decreased when combined with Conjugated estrogens. Cycloguanil The therapeutic efficacy of Cycloguanil can be decreased when used in combination with Leucovorin. Dabrafenib The excretion of Leucovorin can be decreased when combined with Dabrafenib. Dapsone The therapeutic efficacy of Dapsone can be decreased when used in combination with Leucovorin. Dexamethasone The excretion of Dexamethasone can be decreased when combined with Leucovorin. Dexamethasone acetate The excretion of Dexamethasone acetate can be decreased when combined with Leucovorin. Diclofenac The excretion of Leucovorin can be decreased when combined with Diclofenac. Dinoprostone The excretion of Dinoprostone can be decreased when combined with Leucovorin. Dolutegravir The excretion of Leucovorin can be decreased when combined with Dolutegravir. Doripenem The excretion of Doripenem can be decreased when combined with Leucovorin. Dronedarone The excretion of Leucovorin can be decreased when combined with Dronedarone. Eluxadoline The excretion of Eluxadoline can be decreased when combined with Leucovorin. Enalapril The excretion of Leucovorin can be decreased when combined with Enalapril. Enasidenib The excretion of Leucovorin can be decreased when combined with Enasidenib. Esomeprazole The excretion of Leucovorin can be decreased when combined with Esomeprazole. Estradiol The excretion of Estradiol can be decreased when combined with Leucovorin. Famotidine The excretion of Famotidine can be decreased when combined with Leucovorin. Favipiravir The excretion of Leucovorin can be decreased when combined with Favipiravir. Fexinidazole The excretion of Leucovorin can be decreased when combined with Fexinidazole. Fexofenadine The excretion of Fexofenadine can be decreased when combined with Leucovorin. Flucytosine The risk or severity of adverse effects can be increased when Leucovorin is combined with Flucytosine. Fluorescein The excretion of Fluorescein can be decreased when combined with Leucovorin. Fluorouracil The risk or severity of adverse effects can be increased when Leucovorin is combined with Fluorouracil. Fosphenytoin The serum concentration of Fosphenytoin can be decreased when it is combined with Leucovorin. Furosemide The excretion of Leucovorin can be decreased when combined with Furosemide. Ganciclovir The excretion of Leucovorin can be decreased when combined with Ganciclovir. Gemfibrozil The excretion of Leucovorin can be decreased when combined with Gemfibrozil. Glucarpidase The serum concentration of the active metabolites of Leucovorin can be reduced when Leucovorin is used in combination with Glucarpidase resulting in a loss in efficacy. Guanidine The excretion of Leucovorin can be decreased when combined with Guanidine. Hydrochlorothiazide The excretion of Hydrochlorothiazide can be decreased when combined with Leucovorin. Hydrocortisone The excretion of Hydrocortisone can be decreased when combined with Leucovorin. Ibuprofen The excretion of Leucovorin can be decreased when combined with Ibuprofen. Indomethacin The excretion of Leucovorin can be decreased when combined with Indomethacin. Ketoprofen The excretion of Leucovorin can be decreased when combined with Ketoprofen. Lansoprazole The excretion of Leucovorin can be decreased when combined with Lansoprazole. Lenvatinib The excretion of Leucovorin can be decreased when combined with Lenvatinib. Letermovir The excretion of Leucovorin can be decreased when combined with Letermovir. Levocarnitine The excretion of Levocarnitine can be decreased when combined with Leucovorin. Linezolid The excretion of Leucovorin can be decreased when combined with Linezolid. Liothyronine The excretion of Leucovorin can be decreased when combined with Liothyronine. Liotrix The excretion of Leucovorin can be decreased when combined with Liotrix. Melatonin The excretion of Leucovorin can be decreased when combined with Melatonin. Mercaptopurine The excretion of Mercaptopurine can be decreased when combined with Leucovorin. Methotrexate The excretion of Leucovorin can be decreased when combined with Methotrexate. Methyltestosterone The excretion of Leucovorin can be increased when combined with Methyltestosterone. Minocycline The excretion of Leucovorin can be decreased when combined with Minocycline. Novobiocin The excretion of Leucovorin can be decreased when combined with Novobiocin. Oseltamivir The excretion of Oseltamivir can be decreased when combined with Leucovorin. Ouabain The excretion of Leucovorin can be decreased when combined with Ouabain. Oxytetracycline The excretion of Leucovorin can be decreased when combined with Oxytetracycline. Pafolacianine Leucovorin may decrease effectiveness of Pafolacianine as a diagnostic agent. Pantoprazole The excretion of Leucovorin can be decreased when combined with Pantoprazole. Pemetrexed Leucovorin may decrease the excretion rate of Pemetrexed which could result in a higher serum level. Phenobarbital The serum concentration of Phenobarbital can be decreased when it is combined with Leucovorin. Phenylbutazone The excretion of Leucovorin can be decreased when combined with Phenylbutazone. Phenytoin The serum concentration of Phenytoin can be decreased when it is combined with Leucovorin. Piperacillin The excretion of Piperacillin can be decreased when combined with Leucovorin. Piroxicam The excretion of Leucovorin can be decreased when combined with Piroxicam. Polythiazide The excretion of Polythiazide can be decreased when combined with Leucovorin. Pralatrexate The therapeutic efficacy of Pralatrexate can be decreased when used in combination with Leucovorin. Pravastatin The excretion of Leucovorin can be decreased when combined with Pravastatin. Prednisolone phosphate The excretion of Prednisolone phosphate can be decreased when combined with Leucovorin. Primidone The serum concentration of Primidone can be decreased when it is combined with Leucovorin. Probenecid The excretion of Leucovorin can be decreased when combined with Probenecid. Proguanil The therapeutic efficacy of Proguanil can be decreased when used in combination with Leucovorin. Pyrimethamine The therapeutic efficacy of Pyrimethamine can be decreased when used in combination with Leucovorin. Quinapril The excretion of Quinapril can be decreased when combined with Leucovorin. Quinidine The excretion of Leucovorin can be decreased when combined with Quinidine. Raltitrexed The therapeutic efficacy of Raltitrexed can be decreased when used in combination with Leucovorin. Ranitidine The excretion of Ranitidine can be decreased when combined with Leucovorin. Relebactam The excretion of Relebactam can be decreased when combined with Leucovorin. Rifampicin The excretion of Leucovorin can be decreased when combined with Rifampicin. Rosuvastatin The excretion of Rosuvastatin can be decreased when combined with Leucovorin. Salicylic acid The excretion of Leucovorin can be decreased when combined with Salicylic acid. Saxagliptin The excretion of Saxagliptin can be decreased when combined with Leucovorin. Sitagliptin The excretion of Sitagliptin can be decreased when combined with Leucovorin. Succinic acid The excretion of Succinic acid can be decreased when combined with Leucovorin. Sulfasalazine The serum concentration of Leucovorin can be decreased when it is combined with Sulfasalazine. Tafamidis The excretion of Leucovorin can be decreased when combined with Tafamidis. Taurocholic acid The excretion of Taurocholic acid can be decreased when combined with Leucovorin. Tazobactam The excretion of Tazobactam can be decreased when combined with Leucovorin. Tegafur The risk or severity of adverse effects can be increased when Leucovorin is combined with Tegafur. Tenofovir alafenamide The excretion of Tenofovir alafenamide can be decreased when combined with Leucovorin. Tenofovir disoproxil The excretion of Tenofovir disoproxil can be decreased when combined with Leucovorin. Tenoxicam The excretion of Leucovorin can be decreased when combined with Tenoxicam. Teriflunomide The excretion of Leucovorin can be decreased when combined with Teriflunomide. Testosterone The excretion of Leucovorin can be increased when combined with Testosterone. Testosterone cypionate The excretion of Leucovorin can be increased when combined with Testosterone cypionate. Testosterone enanthate The excretion of Leucovorin can be increased when combined with Testosterone enanthate. Tetracycline The excretion of Tetracycline can be decreased when combined with Leucovorin. Trifluridine The excretion of Trifluridine can be decreased when combined with Leucovorin. Trimetrexate The therapeutic efficacy of Trimetrexate can be decreased when used in combination with Leucovorin. Valaciclovir The excretion of Valaciclovir can be decreased when combined with Leucovorin. Valproic acid The serum concentration of Leucovorin can be decreased when it is combined with Valproic acid. Zidovudine The excretion of Leucovorin can be decreased when combined with Zidovudine. Pregnancy and Lactation FDA Pregnancy Category C Pregnancy Animal reproduction studies have not been conducted with leucovorin. It is also not known whether leucovorin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Leucovorin should be given to a pregnant woman only if clearly needed. Lactation It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when leucovorin is administered to a nursing mother. How should this medicine be used?

Leucovorin comes as a tablet to take by mouth. It is usually taken every 6 hours until laboratory tests show it is no longer needed. Sometimes leucovorin is taken on a different schedule, depending on the reason it is needed. Take leucovorin at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take leucovorin exactly as directed. Do not take more…

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