Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

The decrease in serum proteins caused by pegaspargase can increase the toxicity of other medicinal products that are protein bound.

In addition, by inhibiting protein synthesis and cell division, pegaspargase can disturb the mechanism of action of other substances which require cell division for their effect, e.g., methotrexate.
Methotrexate and cytarabine can interact differently with Oncaspar: their prior administration can increase the action of pegaspargase synergistically. If these substances are given subsequently, the effect of pegaspargase can be weakened antagonistically.

Pegaspargase can interfere with metabolism and clearance of other medicinal products, based on its effects on protein synthesis and hepatic function, as well as from its combined use with other chemotherapy products known to interact with CYP enzymes.

The use of Oncaspar can lead to fluctuation in coagulation factors. This can promote the tendency to bleeding and/or thrombosis. Caution is therefore needed when anticoagulants such as coumarin, heparin, dipyridamole, acetylsalicylic acid or non-steroidal anti-inflammatory medicinal products are given concomitantly, or when concomitant chemotherapy regimen including methotrexate, daunorubicin, corticosteroids is administered.

When glucocorticoids (e.g., prednisone) and pegaspargase are given at the same time, alterations in coagulation parameters (e.g., fall in fibrinogen and antithrombin III deficiency, ATIII) can be more pronounced.

Pegaspargase may increase the risk of glucocorticoid-induced osteonecrosis in children and adolescents when both treatments are given simultaneously, with a higher incidence seen in girls, through a potential increase in exposure of dexamethasone. (see sections 4.4 and 4.8).

Immediately preceding or simultaneous treatment with vincristine can increase the toxicity of pegaspargase. Administration of Oncaspar before vincristine may increase the neurotoxicity of vincristine. Therefore, vincristine should be given at least 12 hours prior to administration of Oncaspar in order to minimise toxicity.

An indirect interaction cannot be ruled out between pegaspargase and oral contraceptives due to pegaspargase hepatotoxicity that may impair the hepatic clearance of oral contraceptives. Therefore, the concomitant use of Oncaspar with oral contraceptives is not recommended. Another method than oral contraception should be used in women of childbearing potential (see sections 4.4 and 4.6).

Simultaneous vaccination with live vaccines may increase the risk of severe infections attributable to the immunosuppressive activity of pegaspargase, the presence of the underlying disease and combination chemotherapy (see section 4.4). Vaccination with live vaccines should therefore be given no earlier than 3 months after termination of the entire antileukaemic treatment.