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

(fō-lĭn′ĭk)
n.
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.
References in periodicals archive ?
When comparing folic acid versus folinic acid, a 2013 Cochrane review found no statistically significant difference in efficacy between the two agents.
Anaphylactoid shock due to folinic acid during treatment of metastatic colorectal cancer.
Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases.
However, due to genetic variants in the DHFR enzyme, or variants that can reduce folate, folinic acid and SAMe, BH2 is not converted back into BI-14.
Folate nephropathy occurring during cytotoxic chemotherapy with high-dose folinic acid and 5-fluorouracil.
Folinic acid, at the dose of 12 mg/[m.sup.2] IV was administered to adjust to MTX concentrations according to protocol guidelines, at 36 h after the initiation of MTX infusion and repeated every 6 h until MTX concentration was <0.02 [micro]mol/L.
Bruzzese et al., "Synergistic antitumour effect of raltitrexed and 5-fluorouracil plus folinic acid combination in human cancer cells," Anti-Cancer Drugs, vol.
Jena, "Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid," Mutation Research, vol.
It is also known as folinic acid and is generally used as calcium or sodium folinate.
Because 14 out of 24 lymph nodes had been invaded by the tumor, he had undergone a 28-day period of radiotherapy and 6 chemotherapy sessions with FUFA (5-fluorouracil and folinic acid).
Therapy should include pyrimethamine and sulfadiazine, with folinic acid or clindamycin added.Alternative regimens include, trimethoprim-sulfamethoxazole, pyrimethamine and folinic acid plus one of the drugs e.g.atovaquone, clarithromycin, and azithromycin and dapssone .Corticsosteroids are often given to patients with ocular toxoplasmosis and patients with TE.
As a rule intelligent handling of situation would have been withdrawing of all the drugs immediately and sending their samples to the Drug testing laboratories to pin point the offending drug, treating the patients with folinic acid, steroid and leucovorin and giving compensation to the patients relatives.