DBL Calcium Folinate Special Precautions

HSP Calcium folinate hydrate 10 mg/mL Injection should be administered only by intramuscular or intravenous injection and must not be administered intrathecally. When folinic acid has been administered intrathecally following intrathecal overdose of methotrexate, death has been reported.
HSP Calcium folinate hydrate 10 mg/mL Injection should only be used with folic acid antagonists, e.g., methotrexate, or fluoropyrimidines, e.g., fluorouracil, under the direct supervision of a clinician experienced in the use of cancer chemotherapeutic agents.
Parenteral administration is preferable to oral dosing if there is a possibility that the patient may vomit or not absorb HSP Calcium folinate hydrate 10 mg/mL Injection.
Because of the calcium ion content of the HSP Calcium folinate hydrate 10 mg/mL Injection, no more than 160 mg (16 mL of the 300 mg/30 mL formulation) should be injected intravenously per minute.
Folinic acid may enhance the toxicity of fluorouracil. Deaths from severe enterocolitis, diarrhoea and dehydration have been reported in elderly patients receiving folinic acid and fluorouracil. Concomitant granulocytopenia and fever were present in some, but not all, of the patients.
Seizures and/or syncope have been reported rarely in cancer patients receiving folinic acid, usually in association with fluoropyrimidine administration, and most commonly in those with CNS metastases.
Since three patients had recurrent neurological symptoms on rechallenge with folinic acid, further treatment with folinic acid is not recommended in these circumstances.
Simultaneous therapy with a folic acid antagonist and folinic acid is not recommended because the effect of the folic acid antagonist is either reduced or completely inhibited.
Folinic acid has no effect on nonhaematological toxicities of methotrexate, such as the nephrotoxicity resulting from drug and/or metabolite precipitation in the kidney.
Many cytotoxic medicinal products - direct or indirect DNA synthesis inhibitors - lead to macrocytosis (hydrocarbamide, cytarabine, mercaptopurine, thioguanine). Such macrocytosis should not be treated with folinic acid.
Folinic acid is not suitable for the treatment if pernicious anaemias and other anaemias resulting from lack of vitamin B₁₂. Haematological remissions may occur, while the neurological manifestations remain progressive.
Folinic acid/Methotrexate: An accidental overdose with a folate antagonist, such as methotrexate, should be treated quickly as a medical emergency. As the time interval between methotrexate administration and folinic acid rescues increases, folinic acid effectiveness in counteracting toxicity decreases.
The presence of pre-existing or methotrexate-induced renal insufficiency is potentially associated with delayed excretion of methotrexate and may increase the need for higher doses or more prolonged use of folinic acid. Folinic acid has no effect on non-haematological toxicities of methotrexate, such as nephrotoxicity resulting from drug methotrexate and/or metabolite precipitation in the kidney.
Excessive folinic acid doses must be avoided since this might impair the antitumour activity of methotrexate, especially in CNS tumours where folinic acid accumulates after repeated courses.
Resistance to methotrexate as a result of decreased membrane transport implies resistance to folinic acid rescue as both medicinal products share the same transport system.
Folinic Acid/Fluorouracil: Folinic acid must not be mixed with fluorouracil in the same IV injection or infusion. Folinic acid may enhance the toxicity profile of fluorouracil, particularly in elderly or debilitated patients. Deaths from severe enterocolitis, diarrhoea and dehydration have been reported in elderly patients receiving fluorouracil and folinic acid. Concomitant granulocytopenia and fever were present in some but not all patients. When folinic acid and fluorouracil are used in combination, in cases of toxicity the fluorouracil dosage has to be reduced more than when fluorouracil is used alone.
Combined folinic acid/fluorouracil treatment should not be initiated or maintained in patients with symptoms of gastrointestinal (GI) toxicity, regardless of the severity, until all of these symptoms have completely disappeared. Because diarrhoea may be a sign of GI toxicity, patients presenting with diarrhoea must be carefully monitored until the symptoms have disappeared completely, since rapid clinical deterioration leading to death can occur. If diarrhoea and/or stomatitis occur, it is advisable to reduce the dose of fluorouracil until symptoms have fully disappeared. Especially the elderly and patients with a low physical performance due to their illness are prone to these toxicities.
Seizures and/or syncope have been reported rarely in cancer patients receiving folinic acid, usually in association with fluoropyrimidine administration, and most commonly in those with CNS metastases.
Calcium levels should be monitored in patients receiving combined folinic acid/fluorouracil treatment and calcium supplementation should be provided if calcium levels are low.
Under circumstances leading to delayed methotrexate elimination, treatment with folinic acid may need to be prolonged.
Use in pregnancy (Category A^†): There are no adequate and well-controlled clinical studies conducted in pregnant or breastfeeding woman. No formal animal reproductive toxicity studies with folinic acid have been conducted. There are no indications that folic acid induces harmful effects if administered during pregnancy.
Fluorouracil use is generally contraindicated during pregnancy and contraindicated during breastfeeding; this applies also to the combined use of folinic acid with fluorouracil.
^†Category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without proven increase in frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
Use in lactation: It is not known whether this medicine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when folinic acid is administered to a breastfeeding mother.
Use in Children: There are no data available on use in children.
Use in the elderly: Elderly patients are at increased risk of severe toxicity when receiving combination therapy of folinic acid and fluorouracil. Particular care should be taken when treating these patients.