DrugindexOnline^{2nd edition}

( Citrovorum Factor ; Folinic Acid ) Pronouncation: (loo-koe-VORE-in KAL-see-uhm)
Class: Folic acid derivative

Trade Names:
Wellcovorin
- Tablets 5 mg
- Tablets 25 mg

Lederle Leucovorin Calcium (Canada)

Mechanism of Action

Pharmacology

Acts as antidote to drugs that antagonize folic acid, such as methotrexate.

Pharmacokinetics

Absorption

Following a 25-mg dose C _max is 393 ng/mL (160 to 550 ng/mL), T _max is 2.3 h, and apparent bioavailability is 97% for 25-mg dose.

Metabolism

Metabolites are L-leucovorin, d-leucovorin, and 5-methyl-THF.

Elimination

Terminal t _½ is 5.7 h.

Indications and Usage

Oral and parenteral

Treatment to diminish toxicity and counteract effect of overdosage of folic acid antagonists.

Parenteral

Treatment of megaloblastic anemia caused by folic acid deficiency when oral therapy is not feasible.

Contraindications

Pernicious anemia and other megaloblastic anemias secondary to vitamin B ₁₂ deficiency.

Dosage and Administration

Colorectal Cancer
Adults

IV Either 200 mg/m ² followed by 5-fluorouracil (5-FU) 370 mg/m ² or 20 mg/m ² followed by 5-FU 425 mg/m ² every day for 5 days.

Leucovorin Rescue
Adults

PO / IV / IM 10 mg/m ² every 6 h for 10 doses.

Megaloblastic Anemia Caused by Folic Acid Deficiency
Adults

IV / IM 1 mg/day.

General Advice

• When drug is given for leucovorin rescue after high-dose methotrexate therapy, administer first dose 24 h after beginning methotrexate infusion.
• When drug is given as antidote for inadvertent overdosage of folic acid antagonists (eg, methotrexate), administer as soon as overdose is detected, preferably within first hour.
• Reconstitute parenteral solution using bacteriostatic water for injection or sterile water for injection. Bacteriostatic water mixtures must be used within 7 days; sterile water mixtures, immediately. If doses more than 10 mg/m ² are needed, reconstitute with sterile water for injection.
• Administer IV solution slowly, at rate of less than 160 mg/min, because of calcium content.
• If necessary, further dilution with 100 to 500 mL dextrose or saline solutions for intermittent infusion if possible.
• Tablets can be crushed if necessary.

Storage/Stability

Store at room temperature and protect from light.

Drug Interactions

Barbiturates, hydantoins (eg, phenytoin), primidone

May decrease anticonvulsant activity.

Fluorouracil

Enhances toxicity of fluorouracil.

Methotrexate

May decrease efficacy of intrathecal methotrexate.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Miscellaneous

Hypersensitivity, including anaphylaxis and urticaria. No other adverse reactions have been attributed to leucovorin alone.

Precautions

Monitor Methotrexate levels Ensure that daily methotrexate levels are obtained when leucovorin is used for high-dose methotrexate rescue.

Pregnancy

Category C .

Lactation

Undetermined.

Benzyl alcohol

Present in 1 mL amp and some diluents. Benzyl alcohol has been associated with fatal “gasping syndrome” in premature infants.

5-FU toxicity

Leucovorin enhances toxicity of 5-FU; decrease dosage. Administer only under supervision of health care provider experienced in use of antimetabolite cancer chemotherapy.

Patient Information

• Instruct patient not to double up doses, and to notify health care provider if dose is missed.
• Instruct patient to report the following symptoms to health care provider: nausea, vomiting, diarrhea, sores in mouth, fatigue, difficulty breathing or skin disorders.
• Advise patient to notify health care provider if unable to keep dose down (ie, if vomiting occurs). Patient may need IM or IV therapy instead of oral medication.