Calcium folinate should only be used intravenously or intramuscularly. In the case of intravenous application, not more than 160 mg per minute should be injected due to the calcium content of the solution.
For intravenous infusion, calcium folinate can be diluted before use with 0.9% sodium chloride solution or 5% glucose solution.
Calcium folinate rescue in methotrexate therapy:
As the dosage regimen of the calcium folinate rescue strongly depends on the type and method of application of the medium or high-dose methotrexate application, the methotrexate protocol dictates the dosage regimen of calcium folinate rescue. Therefore, it is best to refer to the medium or high dose methotrexate protocol as regards the type and method of calcium folinate application.
The following guidelines can be used to illustrate the protocols used in adults, the elderly and children: The calcium folinate rescue must be given parenterally to patients with malabsorption syndromes or other gastrointestinal disorders when enteral absorption is not guaranteed. Dosages above 25-50 mg should be given parenterally due to saturable enteral absorption of calcium folinate.
The calcium folinate rescue becomes necessary if methotrexate is given in doses greater than 500 mg/m2
of body surface, and should be considered at doses of 100 mg-500 mg/m2
of body surface.
The dosage and duration of calcium folinate rescue depend primarily on the type and dosage of methotrexate therapy, the appearance of toxicity symptoms and the individual excretion capacity for methotrexate. As a rule, the first dose of calcium folinate 15 mg (6-12 mg/m2
) should be given 12-24 hours (no more than 24 hours) after the start of methotrexate infusion. The same dose is administered every 6 hours during the next 72 hours. After several parenteral doses, one may switch to the oral form.
There are measures in addition to the use of calcium folinate that ensure the prompt excretion of methotrexate (maintaining a high flow of urine and alkalisation of the urine), which are integral to the calcium folinate rescue. Renal function should be monitored by daily measurements of serum creatinine levels.
Residual methotrexate levels should be measured 48 hours after the start of the methotrexate infusion. If the residual methotrexate level is >0.5 μmol/l, the calcium folinate dosages should be adjusted according to the following table: (See table.)
Click on icon to see table/diagram/image
In combination with 5-fluorouracil in cytotoxic therapy:
Different treatment protocols and dosages are used without one dosage having been demonstrated as optimal.
The following regimens have been used in adults and the elderly for the treatment of advanced or metastatic colorectal cancer and are mentioned as examples. No data are available on the application of these combinations in children.
Two-month treatment protocol:
Calcium folinate at 200 mg/m2
as intravenous infusion for 2 hours, followed by 5-FU as a bolus with 400 mg/m2
and 22 hours of infusion of 5-FU (600 mg/m2
) on 2 consecutive days, every 2 weeks on days 1 and 2.
Weekly treatment protocol:
Calcium folinate 20 mg/m2
as i.v. bolus injection or 200-500 mg/m2
as i.v. infusion over 2 hours with 500 mg/m2
fluorouracil as i.v. bolus injection in the middle or at the end of the calcium folinate infusion.
Monthly treatment protocol:
Calcium folinate at a dose of 20 mg/m2
as i.v. bolus injection or 200-500 mg/m2
i.v. infusion, immediately followed by fluorouracil at a dose of 425 or 370 mg/m2
as an i.v. bolus injection on 5 consecutive days.
In combination therapy with fluorouracil, a modification of the fluorouracil doses and the treatment intervals may be necessary based on the condition of the patient, clinical response and dose limiting toxicity, as specified in the product information for fluorouracil. A reduction of the calcium folinate dose is not necessary.
The number of repeat cycles will be decided on by the physician.
Antidote to the folic acid antagonists trimetrexate, trimethoprim, and pyrimethamine: Trimetrexate toxicity: Prevention:
Calcium folinate should be given daily during treatment with trimetrexate and for 72 hours after the last trimetrexate dose. Calcium folinate can be given either intravenously at a dose of 20 mg/m2
for 5-10 minutes every 6 hours until a total daily dose of 80 mg/m2
has been achieved, or it can be given orally divided into 4 doses per day of 20 mg/m2
each at equal intervals. The daily calcium folinate doses should be adjusted depending on the haematological toxicity of trimetrexate.
Overdose (possibly occurring with trimetrexate doses over 90 mg/m2 without concomitant calcium folinate administration):
After discontinuing trimetrexate: Administration of calcium folinate 40 mg/m2
i.v. every 6 hours for 3 days.
Trimethoprim toxicity: After discontinuing trimethoprim:
Administration of calcium folinate 3-10 mg/day until blood count has returned to normal.
In cases of high-dose therapy with pyrimethamine or in cases of longer treatment with low doses, calcium folinate should be used at a dose of 5 to 50 mg/day based on the results of the peripheral blood count.