Classifications: blood former; antianemic agent; antidote; Therapeutic: antianemic; antidote
Pregnancy Category: C
5 mg, 10 mg, 15 mg, 25 mg tablets; 50 mg, 100 mg, 350 mg vials
A reduced form of folic acid; unlike folic acid, it does not require enzymatic reduction and therefore is readily available
to participate in reactions. Functions as an essential cell growth factor. During antineoplastic therapy, it prevents serious
toxicity by protecting cells from the action of folic acid antagonists such as methotrexate.
Antidote against folic acid antagonists such as methotrexate.
Folate-deficient megaloblastic anemias due to sprue, pregnancy, and nutritional deficiency when oral therapy is not feasible.
Also to prevent or diminish toxicity of antineoplastic folic acid antagonists, particularly methotrexate. Also to treat
advanced colorectal cancer when given concurrently with 5-fluorouracil (5-FU).
Undiagnosed anemia, pernicious anemia, or other megaloblastic anemias secondary to vitamin B12 deficiency; intrathecal administration; oral form with stomatitis; pregnancy (category C).
Renal dysfunction, elderly; seizure disorders; lactation.
Route & Dosage
Adult/Child: IV/IM Up to 1 mg/d
Leucovorin Rescue for Methotrexate Toxicity
Adult/Child: PO/IM/IV 10 mg/m2 q6h until serum methotrexate levels are reduced
Leucovorin Rescue for Other Folate Antagonist Toxicity
Adult/Child: PO/IM/IV 515 mg/d
Advanced Colorectal Cancer
Adult: IV 200 mg/m2 followed by fluorouracil 370 mg/m2
- Note: Oral route is NOT recommended for doses higher than 25 mg or if patient is likely to vomit.
- Use 3 mg ampules for IM injection.
- Give deep into a large muscle.
PREPARE: Direct: Give 1 mL (3 mg) ampules, which contain benzyl alcohol, undiluted. IV Infusion: ??For doses <10 mg/m2, reconstitute each 50 mg in 5 mL (10 mg per 1 mL in 10 mL) of bacteriostatic water for injection with benzyl alcohol as
a preservative. For doses >10 mg/m2 reconstitute, as above, but with sterile water for injection without a preservative. Final concentration is 10 mg/mL. ??Further dilute in 100500 mL of IV solutions (e.g., D5W, NS, RL) to yield a concentration of 1020 mg/mL of IV
ADMINISTER: Direct: Give 160 mg or fraction thereof over 1 min. IV Infusion: Do not exceed direct IV rate. Give more slowly if the volume of IV solution to be infused is large.
INCOMPATIBILITIES Solution/additive: Fluorouracil. Y-site: Amphotericin B cholesteryl complex, droperidol, foscarnet, sodium bicarbonate.
- Use solution reconstituted with bacteriostatic water within 7 d. Use solution reconstituted with sterile water for injection
- Protect from light.
Adverse Effects (≥1%)Body as a Whole:
Allergic sensitization (urticaria, pruritus, rash, wheezing). Hematologic:
May enhance adverse effects of fluorouracil;
may reverse therapeutic effects of trimethoprim-sulfamethoxazole.
Within 30 min. Duration:
36 h. Distribution:
Crosses placenta; distributed into breast milk. Metabolism:
In liver and intestinal mucosa
to tetrahydrofolic acid derivatives. Elimination:
8090% in urine, 58% in feces.
Assessment & Drug Effects
- Monitor neurologic status. Use of leucovorin alone in treatment of pernicious anemia or other megaloblastic anemias associated
with vitamin B12 deficiency can result in an apparent hematological remission while allowing already present neurologic damage to progress.
- Lab tests: Do Clcr determinations prior to initiation of leucovorin, urine pH prior to and about every 6 h throughout therapy; daily serum
creatinine levels are recommended to detect onset of kidney function impairment.
Patient & Family Education
- Notify physician of S&S of a hypersensitivity reaction immediately (see Appendix F).