Interactions : אינטראקציות

4.5 Interactions with other medicinal products and other forms of interaction

Leucovorin is an antidote of folic acid antagonists - e.g. methotrexate. Following the use of methotrexate, leucovorin overdose may lead to a loss of the effect of methotrexate therapy ("over - rescue").

Concomitant use of leucovorin counteracts the antineoplastic activity of methotrexate and increases the cytotoxic effects of fluorouracil.

If calcium folinate is administered in combination with a folic acid antagonist (for instance cotrimoxazole, pyrimethamine) the efficacy of the folic acid antagonist may be reduced or completely neutralised.

Calcium folinate can reduce the effect of anti-epileptics like phenobarbital, primidone, phenytoin and succinimides and can increase the frequency of the attacks (a reduction of the plasma concentrations of enzyme inducing anti-convulsants can be observed because the liver metabolism is increased as folates are one of the co-factors)(see also sections 4.4 and 4.8).

Concomitant administration of calcium folinate and 5-fluorouracil appeared to increase the efficacy and the toxicity of 5-fluorouracil (see sections 4.2, 4.4 and 4.8).