CALCIUM FOLINATE Tablet Ref.[7911] Active ingredients: Calcium folinate

Calcium Folinate should only be used with methotrexate or 5-FU under the direct supervision of a clinician experienced in the use of cancer chemotherapeutic agents.

In the treatment of inadvertent overdosage of a folic acid antagonist, folinate should be administered as soon as possible; if a period exceeding 4 hours intervenes, the treatment may not be effective.

In general, Calcium Folinate should not be given simultaneously with folic acid antagonists, e.g. methotrexate, to abort clinical toxicity as the therapeutic effect of the antagonist may be nullified. However, Calcium Folinate given concurrently with folate antagonists, such as pyrimethamine and trimethoprim does not inhibit their antibacterial activity.

Parenteral administration of folinate is preferable to oral dosing following chemotherapy with folic acid antagonists if there is a possibility that the patient may vomit and not absorb the folinate.

Measures to ensure the prompt excretion of methotrexate are important as part of Calcium Folinate Rescue Therapy. These measures include:

1. Alkalinisation of urine so that the urinary pH is greater than 7.0 before methotrexate infusion (to increase solubility of methotrexate and its metabolites)
2. Maintenance of urine output of 1800-2000 cc/m²/24 hr by increased oral or intravenous fluids on days 2, 3 and 4 following methotrexate therapy.
3. Plasma methotrexate concentration, BUN and creatinine should be measured on days 2, 3 and 4.

These measures must be continued until the plasma methotrexate level is less than 10-7 molar (0.1μM).

Folinates given in large amounts may counteract the antiepileptic effect of phenobarbitone, phenytoin and primidone and increase the frequency of seizures in susceptible patients.

Caution is required during concurrent administration of Calcium Folinate with fluoropyrimidine as this has been associated with seizures and syncope (see Section 4.8).

Reproduction studies have been performed in rats and rabbits at doses of at least 50 times the human dose. These studies have revealed no evidence of harm to the foetus due to Calcium Folinate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, Calcium Folinate should only be used in pregnant women if the potential benefit justifies the potential risk to the foetus.

Since it is not known if Folinate is distributed into milk, the drug should be used with caution in nursing women.

Not applicable.

Frequencies are defined using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Immune system disorders

Very rare (<0.01%): allergic reactions, including anaphylactoid/anaphylactic reactions, and urticaria.

Psychiatric disorders

Rare (0.01-0.1%): insomnia, agitation and depression after high doses.

Gastrointestinal disorders

Rare (0.01-0.1%): gastrointestinal disorders after high doses.

Neurological disorders

Rare (0.01-0.1%): increase in the frequency of attacks in epileptics (see also section 4.5 Interactions).

General disorders and administration site conditions

Uncommon (0.1-1%): fever has been observed after administration of calcium folinate as solution for injection.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Immediate precipitation results when Calcium Folinate injection is combined with Droperidol in syringe.