Calcium Folinate

What it is and how it works

Calcium folinate is the calcium salt of 5-formyltetrahydrofolic acid, a reduced folate that does not require dihydrofolate reductase for activation. It therefore bypasses the block produced by methotrexate and other folate antagonists, rescuing normal cells. With fluorouracil it stabilises the binding of the fluorouracil metabolite to thymidylate synthase, enhancing its cytotoxicity.

Indications

Rescue after high-dose methotrexate and treatment of overdose or toxicity of folic acid antagonists; in combination with fluorouracil for colorectal and other cancers; megaloblastic anaemia due to folate deficiency when oral folic acid is not appropriate.

Dosage and administration (summary)

Dosing is according to the oncology protocol: for methotrexate rescue typically about 15 mg (around 10 mg/m²) every 6 hours by injection or orally, starting 24 hours after methotrexate and adjusted according to methotrexate plasma levels; with fluorouracil, doses are set by the specific regimen. Intravenous injection should not exceed 160 mg/min because of the calcium content.

Contraindications

Pernicious anaemia or other megaloblastic anaemia due to vitamin B12 deficiency; intrathecal administration.

Warnings and precautions

Must not be given intrathecally, as this can be fatal. It may mask the haematological signs of vitamin B12 deficiency while neurological damage progresses; when combined with fluorouracil it increases fluorouracil toxicity (especially diarrhoea, mucositis and myelosuppression), particularly in the elderly. It can reduce the efficacy of antiepileptics such as phenobarbital, phenytoin and primidone.

Pregnancy

May be used in pregnancy when indicated; its use is linked to that of methotrexate or fluorouracil, which are themselves contraindicated or hazardous in pregnancy.

Storage and supply

Injection: store at 2–8 °C, protected from light (unless the product information states otherwise). Tablets: store below 25 °C, protected from light.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.