Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

In case of previous or concomitant treatment having adverse effects on the bone marrow (particularly cytostatic agents, irradiation) myelotoxic interactions are possible.

Studies to investigate the presence of phenotypic metabolism have not been undertaken but hydroxylation of the parent compound to metabolites with anti-tumour activity has been identified.

Dacarbazine is metabolised by cytochrome P450 (CYP1A1, CYP1A2, and CYP2E1). This has to be taken into account if other medicinal products are co-administered which are metabolised by the same hepatic enzymes.

Dacarbazine can enhance the effects of methoxypsoralen because of photosensitization.
Immunisation with live vaccines should be avoided during therapy with dacarbazine due to the risk of serious and potentially fatal infections. It is advised to use live virus vaccines with caution after stopping chemotherapy and vaccinate not sooner than 3 months after the last dose of chemotherapy.
It is recommended to use an inactivated vaccine if available (see also section 4.4).

Risk of thrombosis is increased in malignant diseases; therefore, use of concomitant anticoagulation is common. If the patient is to receive oral anticoagulants, the frequency of INR monitoring must be increased due to large interindividual variability in coagulation and due to possible interaction between anticoagulants and cytostatics.

Concomitant use with phenytoin may cause reduced absorption of phenytoin from the gastrointestinal tract and may predispose the patient to convulsions (see section 4.4).

Concomitant use of cyclosporine (and in some cases tacrolimus) must be considered carefully because these agents may cause excessive immunosuppression and lymphoproliferation.

Concomitant use of fotemustine can cause acute pulmonary toxicity (adult respiratory distress syndrome) which may lead to a fatal outcome. Fotemustine and dacarbazine should not be used concomitantly.