creased use of parenteral nutrition.
4.5 Interaction with other medicinal products and other forms of interaction
Limited studies of the interaction of MEPACT with chemotherapy have been conducted. Although these studies are not conclusive, there is no evidence of interference of MEPACT with the anti-tumour effects of chemotherapy and vice versa.
It is recommended to separate the administration times of MEPACT and doxorubicin or other lipophilic medicinal products if used in the same chemotherapy regimen.
The use of MEPACT 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 MEPACT.
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, MEPACT 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.
4.6 Pregnancy and lactation
Pregnancy
There are no data from the use of mifamurtide in pregnant patients. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). MEPACT should not be used during pregnancy and in women not using effective contraception.
Lactation
It is unknown whether mifamurtide is excreted in human milk. The excretion of mifamurtide in milk has not been studied in animals. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy should be made taking into account the benefit of breast-feeding to the child and the benefit of MEPACT therapy to the woman.
4.7 Effects on ability to drive and use machines
No studies of the effects on the ability to drive and use machines have been performed. Some very common or common undesirable effects of MEPACT treatment (such as dizziness, vertigo, fatigue and blurred vision) may have an effect on the ability to drive and use machines.
4.8 Undesirable effects
Each of the 248 patients treated with MEPACT during the early phase single arm studies in patients with mostly advanced malignancies experienced at least one undesirable effect. Many of the most frequently reported undesirable effects as shown in the following summary table are thought to be related to the mechanism of action of mifamurtide. The majority of these events were reported as either mild or moderate. This profile is consistent whether summarising all early studies (n=248) or only those studies in osteosarcoma (n=51). It is likely that und |
