Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Brivudine: A clinically significant interaction between brivudine and fluoropyrimidines (e.g., capecitabine, fluorouracil, tegafur) was reported, which is based on an inhibition of dihydropyrimidine dehydrogenase by brivudine. This interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal. For this reason, brivudine should not be co-administered with fluorouracil (see sections 4.3 and 4.4). After the end of therapy with brivudine, at least 4 weeks must pass before therapy with fluorouracil may be initiated. Therapy with brivudine may be initiated 24 hours after the last dose of fluorouracil.

Any treatment measure that worsens the patient's general condition or interferes with bone marrow function (e.g., other cytotoxic agents) may increase the toxicity of fluorouracil. Fluorouracil may increase the cutaneous toxicity of radiation therapy.

Calcium folinate enhances the action of fluorouracil. Serious, including sometimes lethal, diarrhea may occur as a clinical consequence of this interaction.
An accumulation of such deaths has been reported particularly in the case of the administration regimen of a single weekly I.V. bolus injection of 600 mg/m² body surface area of fluorouracil in combination with calcium folinate.

Concomitant administration of phenytoin and fluorouracil has been reported to increase the plasma levels of phenytoin, which resulted in symptoms of phenytoin intoxication (see section 4.4).

Cimetidine, metronidazole and interferons may increase the plasma levels of fluorouracil. This can increase the toxic effects of fluorouracil.

In female patients who received a thiazide diuretic in addition to cyclophosphamide, methotrexate and fluorouracil, the granulocyte count decreased more than after the same cytostatic cycles not containing thiazide.

In isolated cases, a drop in Quick-type PT was observed in patients treated with warfarin who also received fluorouracil alone or in combination with levamisole.

When treated with fluorouracil and levamisole, hepatotoxic effects (elevated serum levels of alkaline phosphatase, transaminases or bilirubin) are frequently observed.

Female patients with breast cancer who received combination treatment with cyclophosphamide, methotrexate, fluorouracil and tamoxifen displayed an increased risk of developing thromboembolic events.

Co-administration of vinorelbine with fluorouracil/folinic acid may cause severe mucositis leading to death.

The detection methods for bilirubin and 5-hydroxyindoleacetic acid in the urine may reveal elevated or false-positive values.

General comments:
Cytostatic agents may reduce antibody production after influenza vaccination.
Cytostatic agents may increase the risk of infection after the administration of live vaccines.