What is leucovorin

Leucovorin is a form of folic acid. Folic acid helps your body produce and maintain new cells, and also helps prevent changes to DNA that may lead to cancer. Folic acid is present in many foods such as dried beans, peas, oranges, spinach, and others. Leucovorin is used as an antidote to prevent harmful effects of methotrexate (Rheumatrex, Trexall; cancer chemotherapy medication) when methotrexate is used to treat certain types of cancer. Leucovorin is also used to treat people who have accidentally received an overdose of methotrexate or similar medications, pyrimethamine (Daraprim), trimethoprim (Trimpex, Proloprim), and others. Leucovorin is used also to prevent or treat megaloblastic anemia. Leucovorin acts the same way in the body as folic acid, which may be low in these patients. You should not take leucovorin if you have pernicious anemia or other types of anemia caused by a lack of vitamin B12.

Leucovorin is in a class of medications called folic acid analogs. It works by protecting healthy cells from the effects of methotrexate or similar medications while allowing methotrexate to enter and kill cancer cells.

Leucovorin is also used along with fluorouracil (a cancer medicine) to treat cancer of the colon (bowel).

Leucovorin is available only with a prescription.

Leucovorin is available in the following dosage forms:

• Tablet
• Powder for Solution
• Solution

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.

Leucovorin injection comes as a solution (liquid) and a powder to be mixed with liquid and injected intravenously (into a vein) or into a muscle. When leucovorin injection is used to prevent harmful effects of methotrexate or to treat an overdose of methotrexate or a similar medication, it is usually given every 6 hours until laboratory tests show it is no longer needed. When leucovorin injection is used to treat anemia, it is usually given once a day. When leucovorin injection is used to treat colorectal cancer, it is usually given once a day for five days as part of a treatment that may be repeated once every 4 to 5 weeks.

Leucovorin special precautions

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.

Pediatric

• In children with seizures, leucovorin may increase the number of seizures that occur.

Geriatric

• Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of leucovorin in the elderly with use in other age groups.

Pregnancy

• Pregnancy Category C: Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breastfeeding

• There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking leucovorin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using leucovorin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Sulfamethoxazole
• Trimethoprim

Using leucovorin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Capecitabine
• Doxifluridine
• Fluorouracil
• Glucarpidase
• Phenobarbital
• Primidone
• Tegafur

Other interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Kidney disease—Levels of methotrexate may be increased because of its slower removal from the body, so the dose of leucovorin may not be enough to block the unwanted effects of methotrexate
• Nausea and vomiting—Not enough leucovorin may be absorbed into the body to block the unwanted effects of methotrexate

Leucovorin dose

Adult dose for colorectal cancer

Use: For use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.

• 200 mg/m², by slow IV injection (minimum 3 minutes), followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days
  OR
• 20 mg/m², IV, followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days

Comments:

• Do not 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.

Adult dose for methotrexate rescue

Uses: Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages.

Leucovorin Rescue:

• 15 mg (approximately 10 mg/m2), orally, IV, or IM, every 6 hours for 10 doses; start 24 hours after beginning of methotrexate infusion (based on a methotrexate dose of 12 to 15 g/m2 IV over 4 hours)

Impaired Methotrexate Elimination or Inadvertent Overdosage:

• 10 mg/m² orally, IV, or IM, every 6 hours until methotrexate level is less than 10(-8) mol

Comments:

• Determine serum creatinine and methotrexate levels at least once a day.
• Continue leucovorin, hydration, and urinary alkalization until methotrexate levels are below 5 x 10(-8) mol.
• Give parenterally if gastrointestinal toxicity, nausea, or vomiting are present.

Adult dose for methotrexate overdosage

Uses: Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages.

Leucovorin Rescue:

• 15 mg (approximately 10 mg/m²), orally, IV, or IM, every 6 hours for 10 doses; start 24 hours after beginning of methotrexate infusion (based on a methotrexate dose of 12 to 15 g/m² IV over 4 hours)

Impaired Methotrexate Elimination or Inadvertent Overdosage:

• 10 mg/m² orally, IV, or IM, every 6 hours until methotrexate level is less than 10(-8) mol

Comments:

• Determine serum creatinine and methotrexate levels at least once a day.
• Continue leucovorin, hydration, and urinary alkalization until methotrexate levels are below 5 x 10(-8) mol.
• Give parenterally if gastrointestinal toxicity, nausea, or vomiting are present.

Adult dose for megaloblastic anemia

Use: Treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible

• Up to 1 mg, IV or IM, once a day

Comments:

• There is no evidence that doses above 1 mg daily have greater efficacy; additionally, urinary folate loss becomes roughly logarithmic as the amount administered exceeds 1 mg.

Adult dose for folic acid antagonist overdose

Use: Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists.

• 5 to 15 mg orally once a day

Adult dose for pneumocystis pneumonia

Use: Treatment of pneumocystis pneumonia in HIV infected patients

Treatment of pneumocystis pneumonia is not is not a labeled indication.

• 20 mg/m2 or 0.5 mg/kg, IV or orally, every 6 hours, continued for 3 days after last trimetrexate dose

Comments:

• Use in combination with trimetrexate.

Adult dose for pneumocystis pneumonia prophylaxis

Use: Pneumocystis pneumonia prophylaxis in immunocompromised patients

Prophylaxis of pneumocystis pneumonia is not a labeled indication.

• 25 mg, orally, once a week, in combination with dapsone and pyrimethamine

Comments:

• Prophylaxis in HIV infected patients usually begins when the CD4+ count is less than 200 cells/mm or for a history of oropharyngeal candidiasis.
• Prophylaxis is usually discontinued when CD4+ count is 200 cells/mm or higher for 3 months.

Adult dose for toxoplasmosis

Use: Toxoplasmosis treatment

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

Use: For use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.

• 200 mg/m², by slow IV injection (minimum 3 minutes), followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days
  OR
• 20 mg/m², IV, followed by 5-fluorouracil (the manufacturer product information should be consulted), once a day for 5 days

Comments:

• Do not be mix in the same infusion as 5-fluorouracil; a precipitate may form.
• May repeat 5 day treatment course at 4 week (28 day) intervals for 2 courses, then repeat at 4 to 5 week (28 to 35 day) intervals provided the patient is completely recovered from toxicities of the prior course.

Pediatric dose for methotrexate rescue

Uses: Leucovorin rescue after high dose methotrexate therapy; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages.

Leucovorin Rescue:

• 15 mg (approximately 10 mg/m²), orally, IV, or IM, every 6 hours for 10 doses; start 24 hours after beginning of methotrexate infusion (based on a methotrexate dose of 12 to 15 g/m² IV over 4 hours)

Impaired Methotrexate Elimination or Inadvertent Overdosage:

• 10 mg/m² orally, IV, or IM, every 6 hours until methotrexate level is less than 10(-8) mol

Comments:

• Determine serum creatinine and methotrexate levels at least once a day.
• Continue leucovorin, hydration, and urinary alkalization until methotrexate levels are below 0.05 micromol.
• Give parenterally if gastrointestinal toxicity, nausea, or vomiting are present.

Pediatric dose for megaloblastic anemia

Use: Treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible

• Up to 1 mg, IV or IM, once a day

Comments:

• There is no evidence that doses above 1 mg daily have greater efficacy; additionally, urinary folate loss becomes roughly logarithmic as the amount administered exceeds 1 mg.

Pediatric dose for folic acid antagonist overdose

Use: Diminish the toxicity and counteract the effects of inadvertent overdosages of folic acid antagonists.

• 5 to 15 mg orally once a day

Renal dose adjustments

• Data not available

Liver dose adjustments

• Data not available

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Leucovorin side effects

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• diarrhea
• rash
• hives
• itching
• difficulty breathing or swallowing
• seizures
• fainting

Leucovorin may cause other side effects. Call your doctor if you have any unusual problems while taking leucovorin.