Interactions : אינטראקציות

4.5     Interaction with other medicinal products and other forms of interaction

Limited studies of the interaction of mifamurtide with chemotherapy have been conducted.
Although these studies are not conclusive, there is no evidence of interference of mifamurtide with the anti-tumour effects of chemotherapy and vice versa.

It is recommended to separate the administration times of mifamurtide and doxorubicin or other lipophilic medicinal products if used in the same chemotherapy regimen.

The use of mifamurtide concurrently with ciclosporin or other calcineurin inhibitors is contraindicated due to their hypothesised effect on splenic macrophages and mononuclear phagocytic function (see section 4.3).

Also, it has been demonstrated in vitro that high-dose NSAIDs (cyclooxygenase inhibitors) can block the macrophage activating effect of liposomal mifamurtide. Therefore, the use of high-dose NSAIDs is contraindicated (see section 4.3).

Because mifamurtide acts through stimulation of the immune system, the chronic or routine use of corticosteroids should be avoided during treatment with mifamurtide.

In vitro interaction studies showed that liposomal and non-liposomal mifamurtide do not inhibit the metabolic activity of cytochrome P450 in pooled human liver microsomes. Liposomal and non-liposomal mifamurtide do not induce the metabolic activity or the transcription of cytochrome P450 in primary cultures of freshly isolated human hepatocytes. Mifamurtide is, therefore, not expected to interact with the metabolism of substances that are hepatic cytochrome P450 substrates.

In a large controlled randomised study, mifamurtide used at the recommended dose and schedule with other medicinal products that have known renal (cisplatin, ifosfamide) or hepatic (high-dose methotrexate, ifosfamide) toxicities did not exacerbate those toxicities and there was no need to adjust mifamurtide dose.