- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
To be given orally.Although calcium folinate may also be available as a solution for injection, Calcium Folinate should not be administered intrathecally.
Adults and children:Calcium folinate rescue: Depending upon the dose of methotrexate administered, dosage regimens of calcium folinate vary. Up to 120 mg calcium folinate are generally given, usually in divided doses over 12-24 hours by intramuscular injection, bolus intravenous injection or intravenous infusion in normal saline. This is followed by 12-15 mg intramuscularly or 15 mg orally every 6 hours for 48 hours. Rescue therapy is usually started 24 hours after the commencement of methotrexate administration.Neutralising the immediate toxic effects of folic acid antagonists: If overdosage of methotrexate is suspected, the dose of calcium folinate should be equal to or greater than the dose of methotrexate and should be administered within one hour of the methotrexate administration. Megaloblastic anaemia (folate deficiency): One tablet of calcium folinate per day.
Immune system disordersVery rare (<0.01%): allergic reactions, including anaphylactoid / anaphylactic reactions, and urticaria.
Psychiatric disordersRare (0.01-0.1%): insomnia, agitation and depression after high doses.
Gastrointestinal disordersRare (0.01-0.1%): gastrointestinal disorders after high doses.
Neurological disordersRare (0.01-0.1%): increase in the frequency of attacks in epileptics (see also section 4.5 Interactions).
General disorders and administration site conditionsUncommon (0.1-1%): fever has been observed after administration of calcium folinate as solution for injection.
Combination therapy with 5-fluorouracil only:
Generally, the safety profile depends on the applied regimen of 5-fluorouracil due to enhancement of the 5-fluorouracil induced toxicities.Metabolism and Nutritional Disorder: Not known: Hyperammonaemia Blood and lymphatic system disorders: Very common: bone marrow failure, including fatal cases
General disorders and administration site conditionsVery common: (severe) mucosal toxicity, mucositis, including stomatitis and chelitis. Fatalities have occurred as a result of mucositis Skin and subcutaneous tissue disorders: Common: Palmar-Plantar Erythrodysaesthesia
Gastrointestinal disordersVery common (>10%): vomiting and nausea No enhancement of other 5-fluorouracil induced toxicities (e.g. neurotoxicity).
Gastrointestinal disordersVery common (>10%): diarrhoea with higher grades of toxicity, and dehydration, resulting in hospital admission for treatment and even death.
Reporting of suspected adverse reactionsReporting 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 SchemeWebsite: www.mhra.gov.uk/yellowcardBy reporting side effects you can help provide more information on the safety of this medicine
ABSORPTION AND DISTRIBUTIONIn vivo, Calcium Folinate is rapidly and extensively converted to other tetrahydrofolic acid derivatives including 5-methyl tetrahydrofolate, which is the major transport and storage form of folate in the body.Normal total serum folate concentrations have been reported to range from 0.005-0.015 µg/mL. Folate is actively concentrated in CSF, and normal CSF concentrations are reported to be about 0.016-0.021 µg/mL. Normal erythrocyte folate concentrations range from 0.175-0.316 µg/mL. In general, serum folate concentrations less than 0.005 µg/mL indicate folate deficiency and concentrations less than 0.002 µg/mL usually result in megaloblastic anemia. Following I.M. administration of a 15mg (7.5mg/m²) dose in healthy men, mean peak serum folate concentrations of 0.241 µg/mL occur within about 40 minutes. Following oral administration of a 15mg (7.5mg/m²) dose in healthy men, mean peak serum folate concentrations of 0.268 µg/mL occur within about 1.72 hours. Areas under the serum folate concentration-time curves (AUCs) are reported to be about 8% less following I.M. injection in the gluteal region than in the deltoid region and about 12% less following I.M. injection in the gluteal region than following I.V. or oral administration.Tetrahydrofolic acid and its derivatives are distributed to all body tissues; the liver contains about one-half of total body folate stores. In a small number of patients, biliary concentration of folates was about 4.5 times the plasma folate concentration after oral administration of a 2mg dose of Folinate; this is believed to represent the hepatic folate pool rather than excretion of the administered dose.
ELIMINATIONFolinate is excreted in urine, mainly as 10-formyl tetrahydrofolate and 5, 10-methenyl tetrahydrofolate. There is some evidence that 5-methyl tetrahydrofolate may be conserved by the kidneys in preference to 5-formyl tetrahydrofolate (Folinate). Loss of folate in the urine becomes approximately logarithmic as the amount of Folinate administered exceeds 1mg.
Hospira UK Ltd
Horizon, Honey Lane, Hurley, Maidenhead, SL6 6RJ, UK
+44 (0)800 098 8653
+44 (0)1628 515500
0800 0885133 UK or +44 (0)1423 850 671 - Ireland