Allergic sensitisation, including anaphylactoid reactions and urticaria, has been reported following both oral and parenteral administration of folic acid. Nausea and vomiting with very high doses of HSP Calcium Folinate 10 mg/ml Injection have been reported.
In addition, haematological adverse reactions, such as leucocytopenia and thrombocytopenia, may occur. These adverse reactions are dose dependent and their occurrence can usually be decreased by reducing the dosage of cytotoxic drugs. To control these adverse reactions, haematological values e.g., blood leucocyte and thrombocyte levels, and serum electrolyte (e.g. Na, K, Ca) and creatinine levels should be closely monitored.
Immune system disorders:
Frequency undetermined: allergic reactions, urticaria.
Very rare: Anaphylactoid/anaphylactic reactions.
Insomnia, agitation and depression after high doses.
Nervous system disorders:
Increase in the frequency of attacks in epileptics.
Rare: Seizures and/or syncope.
Gastrointestinal disorders after high disorders, abdominal pain.
General disorders and administrations site conditions:
Frequency undetermined: Fever after administration of folinic acid as solution for injection.
Cases of Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), some fatal, have been reported in patients receiving folinic acid in combination with other agents known to be associated with these disorders. A contributory role of folinic acid in these occurrences of SJS/TEN cannot be excluded.
Folinic Acid in combination with fluorouracil:
Generally the safety profile of folinic acid depends on the applied regimen of fluorouracil due to enhancement of fluorouracil-induced toxicities.
The most common dose-limiting adverse reaction occurring in patients receiving combination of HSP Calcium Folinate 10 mg/ml Injection and fluorouracil are stomatitis and diarrhoea. Fatalities have occurred as a result of gastrointestinal toxicity (predominantly mucositis and diarrhoea) and myelosuppression. In patients with diarrhoea, rapid clinical deterioration leading to death can occur (see PRECAUTIONS).
Seizures and/or syncope have been reported rarely in cancer patients receiving HSP Calcium Folinate 10 mg/ml Injection, usually in association with fluoropyrimidine administration (see PRECAUTIONS).
Additional undesirable effects of HSP Calcium Folinate 10 mg/ml Injection when used in combination with fluorouracil are listed as follows: Hepatobiliary disorders:
Frequency undetermined: Hyperammonaemia.
General disorders and administration site condition:
Frequency undetermined: Mucositis, stomatitis, cheilitis.
Skin and subcutaneous tissue disorders:
Frequency undetermined: Palmar-Palmar Erythrodysaesthesia.
Very common: Nausea and vomiting, diarrhoea.