Posology : מינונים

4.2 Posology and Method of Administration

Posology
The use of dacarbazine should be confined to physicians experienced in oncology or haematology.

The following regimes may be used. For further details see current scientific literature.

Malignant melanoma
Dacarbazine can be administered as single agent in doses of 200 to 250 mg/m² body surface area/day as an i.v. injection for 5 days every 3 weeks.
As an alternative to an intravenous bolus injection dacarbazine can be administered as a short-term infusion (over 15 - 30 minutes).
It is also possible to give 850 mg/m² body surface area on day 1 and then once every 3 weeks as intravenous infusion.

Hodgkin's disease
Dacarbazine is administered in a daily dose of 375 mg/m² body surface area i.v. every 15 days in combination with doxorubicin, bleomycin, and vinblastine (ABVD regimen).


During dacarbazine treatment frequent monitoring of blood counts should be conducted as well as monitoring of hepatic and renal function. Since severe gastrointestinal reactions frequently occur, antiemetic and supportive measures are advisable.
Because severe gastrointestinal and haematological disturbances can occur an extremely careful benefit- risk analysis has to be made before every course of therapy with dacarbazine.

Duration of therapy
The treating physician should individually decide about the duration of therapy taking into account the type and stage of the underlying disease, the combination therapy administered and the response to and adverse effects of dacarbazine. In advanced Hodgkin's disease, a usual recommendation is to administer 6 cycles of ABVD combination therapy. In metastasized malignant melanoma, the duration of treatment depends on the efficacy and tolerability in the individual patient.

Renal and/or hepatic impairment
If there is mild to moderate renal or hepatic insufficiency alone, a dose reduction is not usually required. In patients with combined renal and hepatic impairment elimination of dacarbazine is prolonged. However, no validated recommendations on dose reductions can be given currently.

Elderly
As limited experience in elderly patients is available no special instructions for the use in elderly patients can be given.

Paediatric population
No special recommendations for the use of dacarbazine in the paediatric age group can be given until further data become available.


Method of administration
Precautions to be taken before handling or administering the medicinal product Dacarbazine is sensitive to light exposure. All reconstituted solutions should be suitably protected from light also during administration (light-resistant infusion set).
Care should be taken when administering the injection to avoid extravasation into tissues since this will cause local pain and tissue damage. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should be introduced into another vein.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

Rate of administration
Doses up to 200 mg/m2 may be given as a slow intravenous injection. Larger doses (ranging from 200 to 850 mg/m²) should be administered as an i.v. infusion over 15-30 minutes.
It is recommended to test the patency of the vein first with a 5- to 10-ml flush of 0.9 % sodium chloride or 5% glucose solution for infusion. The same solutions should be used after infusion to flush any remaining medicinal product from the tubing.