LEUCOVORIN CALCIUM

LEUCOVORIN CALCIUM
(loo-koe-vor'in)
Classifications: blood former; antianemic agent; antidote;
Therapeutic: antianemic
; antidote
Pregnancy Category: C

Availability

5 mg, 10 mg, 15 mg, 25 mg tablets; 50 mg, 100 mg, 350 mg vials

Action

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.

Therapeutic Effect

Antidote against folic acid antagonists such as methotrexate.

Uses

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).

Contraindications

Undiagnosed anemia, pernicious anemia, or other megaloblastic anemias secondary to vitamin B12 deficiency; intrathecal administration; oral form with stomatitis; pregnancy (category C).

Cautious Use

Renal dysfunction, elderly; seizure disorders; lactation.

Route & Dosage

Megaloblastic Anemia
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 5–15 mg/d

Advanced Colorectal Cancer
Adult: IV 200 mg/m2 followed by fluorouracil 370 mg/m2

Administration

  • Note: Oral route is NOT recommended for doses higher than 25 mg or if patient is likely to vomit.
Intramuscular
  • Use 3 mg ampules for IM injection.
  • Give deep into a large muscle.
Intravenous

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 100–500 mL of IV solutions (e.g., D5W, NS, RL) to yield a concentration of 10–20 mg/mL of IV solution. 

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 immediately.
  • Protect from light.

Adverse Effects (≥1%)

Body as a Whole: Allergic sensitization (urticaria, pruritus, rash, wheezing). Hematologic: Thrombocytosis.

Interactions

Drug: May enhance adverse effects of fluorouracil; may reverse therapeutic effects of trimethoprim-sulfamethoxazole.

Pharmacokinetics

Onset: Within 30 min. Duration: 3–6 h. Distribution: Crosses placenta; distributed into breast milk. Metabolism: In liver and intestinal mucosa to tetrahydrofolic acid derivatives. Elimination: 80–90% in urine, 5–8% in feces.

Nursing Implications

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).

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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