folinic acid


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folinic acid

 [fo-lin´ik]
the 5-formyl derivative of tetrahydrofolic acid, a metabolically active derivative of folic acid used to treat folic acid deficiencies and as an antidote to folic acid antagonists. Called also citrovorum factor and leucovorin.

leucovorin calcium (citrovorum factor, folinic acid)

Calcium Folinate (UK), Lederfolin (UK), Refolinon (UK)

Pharmacologic class: Water-soluble vitamin

Therapeutic class: Vitamin, antidote to folic acid antagonist, antianemic, antineoplastic adjunct

Pregnancy risk category C

Action

Counteracts therapeutic and toxic effects of folic acid antagonists; may enhance therapeutic and toxic effects of fluoropyrimidines used in cancer therapy. Also supplements folic acid in folic acid deficiency.

Availability

Injection (expressed as base): 10 mg/vial, 50 mg/vial, 100 mg/vial, 200 mg/vial, 350 mg/vial, 500 mg/vial

Injection, preservative-free (expressed as base): 10 mg/vial, 50 mg/vial, 200 mg/vial, 350 mg/vial, 500 mg/vial

Tablets: 5 mg, 15 mg, 25 mg

Indications and dosages

Leucovorin rescue after high-dose methotrexate therapy

Adults: 15 mg (approximately 10 mg/m2) P.O., I.M., or I.V. q 6 hours, starting 24 hours after methotrexate infusion begins and continuing until serum methotrexate level drops below 10-8 M. If 24-hour serum creatinine level rises 50% over baseline or if 24-hour methotrexate level exceeds 5 × 10-6 M or 48-hour level exceeds 9 × 10-7 M, increase leucovorin dosage to 100 mg/m2 I.V. q 3 hours and continue hydration and urinary alkalization until methotrexate level drops below 10-8 M.

To reduce toxicity and counteract effects of impaired methotrexate elimination or inadvertent overdose of folic acid antagonist

Adults: 15 mg (roughly 10 mg/m2) I.M., I.V., or P.O. q 6 hours until serum methotrexate level drops below 10-8 M. If 24-hour serum creatinine level rises 50% over baseline or if 24-hour methotrexate level exceeds 5 × 10-6 M or 48-hour level exceeds 9 × 10-7 M, increase leucovorin dosage to 100 mg/m2 I.V. q 3 hours and continue hydration and urinary alkalization until methotrexate level drops below 10-8 M.

Advanced colorectal cancer

Adults: Usually given in one of the following regimens: 200 mg/m2 slow I.V. injection over at least 3 minutes, followed by I.V. injection of 5-fluorouracil (5-FU); or 20 mg/m2 I.V. injection, followed by I.V. injection of 5-FU. Treatment is repeated daily for 5 days, and may then be repeated at 28-day intervals for two courses and then at 4- to 5-week intervals, as prescribed.

Megaloblastic anemia secondary to folic acid deficiency

Adults: Up to 1 mg I.M. daily

Dosage adjustment

• In leucovorin rescue after high-dose methotrexate therapy: delayed early or late methotrexate elimination (serum methotrexate level still above 0.2 µM at 72 hours and above 0.05 µM [5 × 10-8] at 96 hours after administration)
• Evidence of acute renal injury

Contraindications

• Treatment of pernicious anemia and other megaloblastic anemias caused by vitamin B12 deficiency

Precautions

Use cautiously in:
• anemia (when vitamin B12 deficiency has been ruled out)
• patients receiving 5-FU concomitantly
• pregnant or breastfeeding patients
• children.

Administration

Recheck leucovorin dosage in current published protocols before giving as methotrexate rescue.
• Give parenterally in patients with GI toxicity, nausea, or vomiting.
• Reconstitute leucovorin injection with sterile or bacteriostatic water for injection containing benzyl alcohol. (When giving with 5-FU for colorectal cancer in dosages above 10 mg/m2, reconstitute only with sterile water for injection.)

Don't mix leucovorin injection with 5-FU, because precipitation will occur.

Give I.V. leucovorin slowly (no faster than 160 mg/minute) because of calcium content. Large doses may be infused over 1 to 6 hours as directed.

Don't give intrathecally; drug may be harmful or fatal by this route.
• Be aware that P.O. dosages above 25 mg are not recommended.

Adverse reactions

Skin: urticaria

Other: allergic sensitization reactions, anaphylactoid reactions

Interactions

Drug-drug.5-FU: enhanced fluorouracil toxicity

Methotrexate, other folic acid antagonists: negated therapeutic and toxic effects of these drugs

Phenobarbital, phenytoin, primidone: negated anticonvulsant effect, increased frequency of seizures in susceptible children

Patient monitoring

Monitor serum creatinine and methotrexate levels every 24 hours.

Monitor closely for adverse reactions. Continue leucovorin therapy, hydration, and urinary alkalization until serum methotrexate level drops below 10-8 M.

Monitor CBC with white cell differential and platelet count before leucovorin/5-FU therapy starts. Repeat weekly during first two courses and then once each cycle at anticipated white blood cell nadir.
• Check electrolyte levels and liver function tests before each treatment for first three cycles. Thereafter, check before every other cycle.
• Assess for adequate hydration when giving with 5-FU or high-dose methotrexate.
• Watch for hypersensitivity reactions, especially anaphylactoid reactions.

Patient teaching

• Teach patient about drug and protocol.

Stress importance of taking leucovorin as prescribed with high-dose methotrexate therapy. Emphasize that it's not just a vitamin.
• Tell patient to immediately report signs or symptoms of allergic reaction, such as hives.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

fo·lin·ic ac·id

(fō-lin'ik as'id),
1. The active form of folic acid that acts as a formyl group carrier in transformylation reactions; the calcium salt, leucovorin calcium, has therapeutic use.
2. The term is occasionally applied to other folates.

folinic acid

/fo·lin·ic ac·id/ (fo-lin´ik) leucovorin; the 5-formyl derivative of tetrahydrofolic acid; it can act as a coenzyme carrier in certain folate-mediated reactions and is used, as the calcium salt leucovorin calcium, in the treatment of some disorders of folic acid deficiency.

folinic acid

(fō-lĭn′ĭk)
n.
Leucovorin.

folinic acid

[fōlin′ik]
an active form of folic acid. It is used to treat megaloblastic anemias that are not caused by vitamin B12 deficiency and to counteract the toxic effects of antineoplastic folic acid antagonists, such as methotrexate. Also called citrovorum factor, leucovorin.

fo·lin·ic ac·id

(fō-lin'ik as'id)
The active form of folic acid, which acts as a formyl group carrier in transformylation reactions; the calcium salt, leucovorin calcium, has therapeutic use.
Synonym(s): citrovorum factor.

folinic acid

A drug used to treat MEGALOBLASTIC ANAEMIA that has resulted from folic deficiency. A brand name is Refolinon.

folinic acid

5-formyltetrahydrofolic acid, a metabolically active derivative of folic acid used to treat folic acid deficiency and as an antidote to folic acid antagonists. Called also citrovorum factor, CF, leucovorin, 5-formyltetrahydropteroylglutamic acid.
References in periodicals archive ?
Recently a number of studies have demonstrated the protective role of folinic acid (FA), a metabolically active form of folic acid, against RA embryopathy.
The MTHFR A 1298C variant impacts the production of folinic acid, which is needed to make BH4, and inhibits the conversion of BH2 to BH4.
Treatment of intrathecal methotrexate overdose with folinic acid rescue and lumbar cerebrospinal fluid exchange: a report of two cases.
Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer.
Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer.
Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution.
This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down syndrome, conclude the authors.
However, despite pleurocentesis and administration of prolonged intravenous folinic acid rescue to counteract methotrexate toxicity, the patient developed confluent blisters on his lower limbs that healed spontaneously with regular dressings.
The first patient was a 61-year-old woman with colorectal carcinoma and liver metastasis, who underwent chemotherapy consisting of 6 cycles of oxaliplatin (the FOLFOX scheme, a chemotherapy regimen consisting of fluorouracil [5 FU], folinic acid, and oxaliplatin).
The mechanism by which MTX causes hepatotoxicity results from binding to the enzyme dihydrofolic reductase, thus preventing conversion of folic acid to its active form, folinic acid.
A dose of 5-10 mg of folinic acid (also known as leucovorin), delivered 24 hours after the methotrexate dose, may reduce toxicity.