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Oral formulations containing calcium folinate

Drugs List

  • calcium folinate 15mg tablets
  • REFOLINON 15mg tablets
  • Therapeutic Indications


    Anaemia - megaloblastic due to folic acid deficiency
    Neutralisation of immediate toxic effects of folic acid antagonists

    Unlicensed Uses

    Metabolic disorders leading to folate deficiency



    Calcium Folinate Rescue

    Treatment should commence 24 hours after initiation of the methotrexate infusion and should be given over 12 to 24 hours.

    The regimen for treatment is dependent on the dose of methotrexate administered. Treatment is initially administered by intramuscular or intravenous bolus or intravenous infusion. Please consult the dosage instructions for calcium folinate injections. After initial treatment, the regimen may be continued with 15 mg of calcium folinate orally every 6 hours for 48 hours.

    An over-rescue may impair the efficacy of methotrexate.

    Megaloblastic anaemia due to folate deficiency

    15 mg of calcium folinate once per day.


    Calcium Folinate Rescue
    (See Dosage; Adult)

    Megaloblastic anaemia due to folate deficiency
    (See Dosage; Adult)
    Some brands suggest that more suitable formulations are available.


    Pernicious anaemia
    Vitamin B12 deficiency

    Precautions and Warnings

    Glucose-galactose malabsorption syndrome
    Lactose intolerance

    Folinic acid rescue: administer 24 hrs after start of methotrexate infusion
    Some formulations contain lactose
    Replace with IV preparation in patients with severe vomiting
    Treatment to be administered by or under supervision of specialist
    Interrupt or reduce dose if significant gastrointestinal disturbances occur

    Measures to ensure the prompt excretion of methotrexate should be carried out in conjunction with calcium folinate administration. The following measures should continue until the plasma level of methotrexate is below 0.1 micromolar:
    Ensuring the alkalinisation of urine (pH greater than 7.0) before initiating methotrexate infusion;
    Ensuring a urinary output of 1.8 to 2 litres/metre squared/day;
    Measuring plasma methotrexate concentration, BUN and creatinine on days 2, 3 and 4.

    Calcium folinate should not be given simultaneously with an anti-neoplastic folic acid antagonist for the purpose of reducing or preventing clinical toxicity. This is because the therapeutic effect of the antagonist may be nullified. However, calcium folinate will not inhibit the antibacterial activity of other folic acid antagonists (such as pyrimethamine or trimethoprim).

    In the event of a folic acid antagonist overdose, folinate should be administered as soon as possible, ideally in under 4 hours, otherwise the treatment may not be effective.

    Pregnancy and Lactation


    Use calcium folinate with caution during pregnancy.

    Animal studies, exposing rats to 50 times the human dose of calcium folinate, have revealed no evidence of harm to the foetus. However, at the time of writing, there have been few reported, well controlled studies regarding the use of calcium folinate in human pregnancy. Consequently, calcium folinate should only be used in pregnancy if the expected benefit outweighs any potential risk to the foetus.

    Calcium folinate is a derivative of the active metabolite of folic acid. It is unknown if calcium folinate crosses the placenta but folic acid does cross the placental barrier (Briggs, 2015).

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Use calcium folinate with caution during breastfeeding.

    Calcium folinate can be used cautiously during breast feeding if considered necessary with regards to the indications. It is unknown if calcium folinate is excreted into human breast milk.

    Calcium folinate is a derivative of the active metabolite of folic acid and The American Academy of Paediatrics suggests that maternal use of folic acid is compatible with breastfeeding (Briggs, 2015).

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Side Effects

    Allergic reaction
    Anaphylactic reaction
    Anaphylactoid reaction
    Exacerbation of epilepsy
    Gastrointestinal disorder
    Sleep disturbances


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: May 2017

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

    Summary of Product Characteristics: Calcium Folinate 15 mg Tablets. Generics UK T/A Mylan. Revised August 2016.

    Summary of Product Characteristics: Calcium Folinate 15 mg Tablets. Hospira UK Ltd. Revised July 2016.

    Summary of Product Characteristics: Refolinon Tablets. Pfizer Limited. Revised November 2016.

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