Leucovorin

Leucovorin is a prescription medication used to treat Methotrexate Overdose, High Dose Methotrexate Rescue, Megaloblastic Anemia Due to Folate Deficiency, Advanced Colorectal Carcinoma (with 5FU), Methanol Poisoning, and Trimethoprim Toxicity.

• Leucovorin is available under different brand names.

Adult and pediatric dosage

Tablets

• 5mg
• 10mg
• 15mg
• 25mg

Injection, powder for reconstitution

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

Injectable solution

• 10mg/mL

Methotrexate Overdose

Adult and pediatric dosage

• Administer as soon as possible and within 24 hours methotrexate level is greater than 10-6 M or 48 hours level is over 9x10-7 M, the dose of leucovorin should be increased to 100 mg/m2 IV every 3 hours until methotrexate level is less than 10-8 M. 

High Dose Methotrexate Rescue

Adult and pediatric dosage

• 10 mg/m2 IV every 6 hours for 10 doses; starts 24 hours after beginning of methotrexate infusion. 
• May give orally after 1st IV dose

Megaloblastic Anemia Due to Folate Deficiency 

Adult and pediatric dosage

• Up to 1 mg daily; there is no evidence that doses greater than 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

Advanced Colorectal Carcinoma (with 5FU)

Adult dosage

• Recommended 20 mg/m2 IV followed by 425 mg/m2 fluorouracil
• Dose reduction treatment pause may be necessary based on hematologic toxicity 

Methanol Poisoning

Adult dosage

• 1 mg/kg (50-70 mg adults) IV every 4-6 hours

Trimethoprim Toxicity

Adult and pediatric dosage

• 10 mg/m2 orally every 6 hours

Dosage Considerations – Should be Given as Follows: 

• See "Dosages."

Common side effects of Leucovorin include:

• hives,
• infection, 
• nausea, 
• vomiting, 
• diarrhea, 
• constipation, 
• oral inflammation, 
• cold sores, 
• fatigue, 
• hair loss, and
• loss of appetite 

Serious side effects of Leucovorin include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, and
• severe dizziness

Rare side effects of Leucovorin include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Leucovorin has severe interactions with no other drugs. 
• Leucovorin has serious interactions with the following drug:
  • trimethoprim
• Leucovorin has moderate interactions with the following drugs:
  • capecitabine
  • fluorouracil
  • glucarpidase 
• Leucovorin has minor interactions with no other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• Vitamin B12 deficiency anemia and pernicious anemia

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Leucovorin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Leucovorin?”

Cautions

• Hypersensitivity reactions including anaphylactoid reactions and 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 (e.g., 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 (i.e., 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 over 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-fluorouracil 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

Pregnancy and Lactation

• Use with caution if benefits outweigh risks in pregnancy. 
• Not known whether distributed in breast milk; use caution.