Indication

Colorectal cancer, Methotrexate toxicity, Megaloblastic anaemia

Adult Dose

Oral Antidote for methotrexate toxicity Adult: 15 mg every 6 hr for 10 doses starting 24 hr after the start of methotrexate infusion. Continue admin until serum levels of methotrexate is <0.05 micromolar. May also be given via IM/IV inj. Folate-deficient megaloblastic anaemia Adult: 15 mg daily. Intravenous Adjunct to fluorouracil in colorectal cancer Adult: 200 mg/m2 BSA by slow IV inj over at least 3 min followed by 370 mg/m2 fluorouracil by IV inj. Treatment is given for 5 consecutive days and repeated at intervals of 28 days for 2 courses. Subsequently, may repeat at 4-5 wkly intervals if the patient has recovered completely from the toxic effects of the prior treatment course. Intramuscular Folate-deficient megaloblastic anaemia Adult: Up to 1 mg/day.

Contraindication

Hypersensitivity, pernicious anaemia and other megaloblastic anaemias secondary to vit B12-deficiency, intrathecal and intraventricular admin.

Mode of Action

Calcium folinate enters the cells as 5-methyl tetrahydrofolate and supplies the cofactor blocked by methotrexate. It stabilises the binding of 5-dUMP and thrymidylate synthetase, enhances flourouracil activity and neutralises the effects of folic acid antagonists such as methotrexate but increases those of 5-fluorouracil.

Precaution

Undiagnosed megaloblastic anaemia, folate dependent tumors; pregnancy. Monitor calcium levels in patients receiving combined 5-Fluorouracil/Folinic acid treatment. To be given parenterally in the presence of GI toxicity, nausea or vomiting. Monitor serum levels of methotrexate to determine the optimal dose and duration of folinic acid admin. Monitor CBC, electrolytes and liver function tests before and regularly during treatment.

Side Effect

Allergic sensitisation, rash, pruritus, eythema, urticaria, nausea, vomiting, pyrexia.

Interaction

Fluorouracil: Folinic acid may increase the toxicity associated with fluorouracil if the two are administered together. Some adverse effects that have occurred, particularly in elderly patients, include severe enterocolitis, diarrhea, and dehydration. Sulfamethoxazole-trimethoprim: A potential drug interaction exists with concomitant use of sulfamethoxazole-trimethoprim and folinic acid. Folinic acid has been shown to decrease the efficacy of sulfamethoxazole-trimethoprim in the treatment of pneumocystis carinii, a common cause of pneumonia in AIDs patients