Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Following previous therapy with L-asparaginase, cytarabine can lead to acute pancreatitis.
Myelotoxic interactions with other treatment methods which may have a toxic effect on the bone marrow (especially other cytostatics and radiation therapy) must be expected according to the current co-medication.


5-fluorocytosine
5-fluorocytosine should not be administered with cytarabine as the therapeutic efficacy of 5-fluorocytosine has been shown to be inhibited during such therapy. Limited data indicates that cytarabine may antagonise the anti-infective effect of 5-fluorocytosine, possibly through competitive inhibition of the anti-infective intake by fungi.

Cardiac glycosides
The gastrointestinal absorption of oral digoxin tablets can be significantly reduced in patients receiving a combined chemotherapy (including cytarabine chemotherapy), possibly due to transient damage of the intestinal mucosa by cytostatics.
In patients who received beta-acetyldigoxin and chemotherapeutic treatment with cyclophosphamides, vincristine and prednisone with or without cytarabine or procarbazine, a reversible decrease in steady-state digoxin levels and reduced renal glycoside elimination occurred.
Limited data suggest that the extent of gastrointestinal absorption of digitoxin is not significantly affected by concomitant administration of combined chemotherapy known to decrease digoxin absorption. Therefore, plasma digoxin levels should be monitored in patients receiving similar chemotherapeutic combined treatments. The use of digitoxin in these patients can be considered as an alternative.

Anti-infectives
An in-vitro interaction study of gentamicin and cytarabine showed a cytarabine-related antagonism regarding the susceptibility of K. pneumoniae strains. In patients receiving cytarabine who were treated with gentamicin for a K. pneumoniae infection, the lack of immediate response to gentamicin may require a re-evaluation of the antibacterial therapy.

Methotrexate
Intravenous cytarabine administered concomitantly with intrathecal methotrexate may increase the risk of severe neurological undesirable effects such as headaches, paralysis, coma, and stroke-like episodes (see section 4.4).

Furthermore, at least 4 weeks must pass between treatment with Alexan and brivudine, sorivudine, and analogues.
If applicable, determination of DPD enzyme activity is indicated prior to the treatment with Alexan.
In concomitant administration of phenytoin and Alexan, an increase of phenytoin plasma concentration has been reported, resulting in symptoms of phenytoin intoxication (see also section 4.4).

Cytarabine can interfere with the determination of the protein fraction in the cerebrospinal fluid by turbidimetry (turbidity measurement) or by the Folin-Ciocalteu method.