Posology : מינונים

4.2   Posology and method of administration

Methotrexate should only be prescribed by doctors with experience in the use of methotrexate and who are fully familiar with the risks associated with a methotrexate treatment.

WARNINGS
The dose must be carefully adjusted to the body surface area if methotrexate is used to treat tumour diseases.
Cases of intoxication with fatal outcome have been reported after the administration of incorrectly calculated doses. The medical personnel and the patients must be comprehensively informed about the toxic effects.



Dose

Malignant tumors and hemoblastoses:
In polychemotherapy of malignant tumors and hemoblastoses the dosage of methotrexate has to be adjusted according to the indication, general condition and the blood counts of the patient.
The administered dose in conventional low-dose MTX therapy (single dose lower than 100 mg/m2), medium-dose MTX therapy (single dose 100 mg/m2–1000 mg/m2) and high-dose MTX therapy (single dose higher than 1000 mg/m2) depends on the respective therapy protocol.

The following dosage instructions are only guidelines:
Conventional dose of methotrexate therapy – no calcium folinate rescue required: 15–20 mg/m2 IV - twice weekly
30–50 mg/m2 IV - once weekly
15 mg/m2/day IV/IM - given at 2–3 weeks intervals

Intermediate dose of methotrexate therapy:
50–150 mg/m2 IV injection; no calcium folinate rescue required, given at 2–3 weeks intervals 240 mg/m2 IV infusion over 24 h; calcium folinate rescue required, given at 4–7 days intervals
500–1000 mg/m2 IV infusion over 36–42 h; calcium folinate rescue required, given at 2–3 weeks intervals

High-dose methotrexate therapy – calcium folinate rescue required:
1–12 gm/m2 IV over 1–6 hours, given at 1–3 weeks intervals

For intrathecal or intraventricular methotrexate therapy a maximum dose of 15 mg/m2 is administered.
Intrathecal route of administration: 0.2–0.5 mg/kg or 8–12 mg/m2 methotrexate is administered every 2–3 days, after disappearance of the symptoms at weekly intervals, and subsequently at monthly intervals until CSF findings return to normal. Prophylactic intrathecal instillation should be carried out every 6–8 weeks.


Method of administration
For intravenous, intramuscular, intra-arterial, intrathecal and intraventricular use after dilution.

Methotrexat “EBEWE” 500 mg, 1000 mg and 5000 mg – concentrate for infusion has to be diluted with standard solutions for infusions before administration according to therapy protocol and duration of infusion. Use 5% glucose solution or physiological saline solution.
Generally 1–2% methotrexate solution is administered (in osteosarcoma higher concentrations are described in the literature).
These methotrexate solutions for infusion are stable at room temperature over 24 hours when exposed to light or protected from light. If longer infusion period is required, the infusion bags/bottle should be changed.
Dosages higher than 100 mg/m2 are generally administered as IV infusion.
Avoid contact with skin or mucosa.
For single use only!