This site is intended for UK healthcare professionals
Medscape UK Univadis Logo
Medscape UK Univadis Logo

Calcium folinate parenteral


Parenteral formulations of calcium folinate.

Drugs List

  • calcium folinate 100mg/10ml injection (solution)
  • calcium folinate 15mg/2ml injection (solution)
  • calcium folinate 200mg/20ml solution for injection vial
  • calcium folinate 300mg/30ml injection (solution)
  • calcium folinate 350mg/35ml solution for injection vial
  • calcium folinate 500mg/50ml solution for injection vial
  • calcium folinate 50mg/5ml injection (solution)
  • Therapeutic Indications


    Cytotoxic therapy in combination with 5-fluorouracil
    Neutralisation of immediate toxic effects of folic acid antagonists

    To diminish toxicity and counteract the action of folic acid antagonists ('folinate rescue') such as methotrexate.

    Treatment of suspected methotrexate overdosage.

    In combination with 5-fluorouracil in cytotoxic therapy.

    Unlicensed Uses

    Metabolic disorders leading to folate deficiency


    Due to the complexity and specialist nature of dosage regimens for this agent, specific dosing information is not included.
    Doses may vary significantly if this agent is used as monotherapy or different combinations.
    When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.


    For intramuscular injection, intravenous injection or intravenous infusion only. Maximum administration rate of 160mg per minute.


    Gastrointestinal toxicity - if combined with 5-fluorouracil therapy
    Pernicious anaemia
    Severe diarrhoea - if combined with 5-fluorouracil therapy
    Vitamin B12 deficiency

    Precautions and Warnings

    Recent radiotherapy
    Restricted sodium intake
    Epileptic disorder
    Renal impairment

    May mask pernicious anaemia or vitamin B12 deficiency
    Not suitable for treatment of cytotoxic induced macrocytosis
    Calcium supplements may be required if risk of calcium/vitamin D deficiency
    Not all available brands are licensed for all indications
    Treatment to be initiated and supervised by a specialist
    Consult local policy on the safe use of anti-cancer drugs
    Folinic acid rescue: ensure adequate hydration and alkalinisation of urine
    Staff: Not to be handled by pregnant staff
    Concurrent methotrexate: monitor serum methotrexate levels
    Monitor adverse reactions, especially gastrointestinal toxicity
    Monitor antiepileptic drug treatment
    Monitor serum creatinine daily
    Monitor toxicity - discontinue or modify dose if necessary
    Advise patient to report diarrhoea and/or stomatitis immediately
    Suspend treatment if gastrointestinal toxicity occurs
    Combination myelosuppressive drug therapy may necessitate dose adjustment

    Serum monitoring of the folic acid antagonist is essential in determining dosage and duration of calcium folinate treatment. Antagonist excretion may be delayed by third space fluid accumulation, renal insufficiency, inadequate hydration, non steroidal anti-inflammatory drugs or salicylate drugs. In these cases, higher doses and prolonged treatment with calcium folinate may be required.

    Avoid excessive doses of calcium folinate as this may impair the anti-tumour activity of methotrexate. This should especially be observed in CNS tumours as calcium folinate accumulates here after repeated doses.

    Resistance to methotrexate as a result of decreased membrane transport also implies resistance to folinate rescue as both medicinal products share the same transport system.

    Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure and methotrexate associated toxicities. Renal insufficiency is potentially associated with delayed excretion of methotrexate and may increase the need for higher doses or more prolonged use of calcium folinate.

    Pregnancy and Lactation


    Use calcium folinate with caution in pregnancy.

    Calcium folinate is a derivative of the active metabolite of folic acid. It is unknown if calcium folinate crosses the placenta, but folic acid is known to cross the placental barrier. Briggs considers that calcium folinate itself is compatible for use in pregnancy if the potential risk justifies its use, but concurrent therapies must be considered.

    There should be no limitations on the use of calcium folinate during pregnancy when used as folinate rescue from toxicity or to counteract the effects of a folic acid antagonist.

    Calcium folinate is contraindicated in pregnancy when used in combination therapy with 5-fluorouracil.


    Use calcium folinate with caution in breastfeeding.

    The manufacturer states that calcium folinate can be used during breastfeeding when considered necessary. It is unknown if calcium folinate is excreted into breast milk.

    There are currently no adequate or well controlled studies in breastfeeding women. The manufacturers suggest that calcium folinate may be used during breastfeeding if considered clinically necessary. Briggs (2015) considers calcium folinate acid compatible with breastfeeding.

    Concurrent therapies must be considered.

    Side Effects

    Anaphylactic shock
    Anaphylactoid reaction
    Bone marrow failure
    Disturbances of gastrointestinal function
    Exacerbation of epilepsy
    Gastro-intestinal toxicity
    Hypersensitivity reactions
    Injection site reactions
    Mucosal toxicity
    Palmar-plantar erythrodysaesthesia


    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: March 2019

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Summary of Product Characteristics: Calcium folinate 3mg/ml solution for injection. Hospira. Revised January 2018.
    Summary of Product Characteristics: Calcium folinate 7.5mg/ml solution for injection. Hospira. Revised January 2018.
    Summary of Product Characteristics: Calcium folinate 10mg/ml solution for injection. Hospira. Revised January 2018.

    Summary of Product Characteristics: Calcium folinate 10mg/ml solution for injection. Consilient Health Ltd. Revised April 2017 .

    Summary of Product Characteristics: Calcium folinate 10 mg/ml solution for injection. TEVA UK Ltd. Revised February 2008.

    Summary of Product Characteristics: Refolinon Injection 3 mg/ml. Pfizer Ltd. Revised May 2016.

    Summary of Product Characteristics: Calcium folinate 10mg/ml solution for injection or infusion. Fresenius Kabi. Revised October 2020.

    NICE Evidence Services Available at: Last accessed: 10 May 2022

    Access the full UK drug database with a FREE Medscape UK Account
    It takes just a few minutes, and you’ll get unlimited access to information on over 11,000 UK drugs.
    Register for Free

    Already a member? Log in

    Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content

    FDB Logo

    FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.