Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Hospira UK Limited, Horizon, Honey Lane, Hurley, Maidenhead, SL6 6RJ, United Kingdom
Folinate is a derivative of tetrahydrofolic acid, the reduced form of folic acid, which is involved as a cofactor for 1-carbon transfer reactions in the biosynthesis of purine and pyrimidines of nucleic acids.
Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective DNA synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Because of its ready conversion to other tetrahydrofolic acid derivatives, Folinate is a potent antidote for both hematopoietic and reticuloendothelia toxic effects of folic acid antagonists, (e.g. Methotrexate, Pyrimethamine, Trimethoprim). It is postulated that in some cancers, Folinate enters and “rescues” normal cells from the toxic effects of folic acid antagonists, in preference to tumour cells, because of a difference in membrane transport mechanisms; this principle is the basis of high-dose Methotrexate therapy with “Folinate rescue”.
In vivo, Calcium Folinate is rapidly and extensively converted to other tetrahydrofolic acid derivatives including 5-methyl tetrahydrofolate, which is the major transport and storage form of folate in the body.
Normal total serum folate concentrations have been reported to range from 0.005-0.015 µg/mL. Folate is actively concentrated in CSF, and normal CSF concentrations are reported to be about 0.016-0.021 µg/mL. Normal erythrocyte folate concentrations range from 0.175-0.316 µg/mL.
In general, serum folate concentrations less than 0.005 µg/mL indicate folate deficiency and concentrations less than 0.002 µg/mL usually result in megaloblastic anemia. Following I.M. administration of a 15mg (7.5mg/m²) dose in healthy men, mean peak serum folate concentrations of 0.241 µg/mL occur within about 40 minutes. Following oral administration of a 15mg (7.5mg/m²) dose in healthy men, mean peak serum folate concentrations of 0.268 µg/mL occur within about 1.72 hours. Areas under the serum folate concentration-time curves (AUCs) are reported to be about 8% less following I.M. injection in the gluteal region than in the deltoid region and about 12% less following I.M. injection in the gluteal region than following I.V. or oral administration.
Tetrahydrofolic acid and its derivatives are distributed to all body tissues; the liver contains about one-half of total body folate stores. In a small number of patients, biliary concentration of folates was about 4.5 times the plasma folate concentration after oral administration of a 2mg dose of Folinate; this is believed to represent the hepatic folate pool rather than excretion of the administered dose.
Folinate is excreted in urine, mainly as 10-formyl tetrahydrofolate and 5, 10-methenyl tetrahydrofolate. There is some evidence that 5-methyl tetrahydrofolate may be conserved by the kidneys in preference to 5-formyl tetrahydrofolate (Folinate). Loss of folate in the urine becomes approximately logarithmic as the amount of Folinate administered exceeds 1mg.
There is no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
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