Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use
Carmustine may be administered only by specialists experienced in the field of chemotherapy.

Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis has been reported to occur with a frequency ranging up to 30%. This may occur within 3 yearsof therapy and appears to be dose related with cumulative doses of 1200-1500 mg/m2being associated with increased likelihood of lung fibrosis. Risk factors include smoking, the presence of a respiratory condition, pre-existing radiographic abnormalities, sequential or concomitant thoracic irradiation and association with other agents that cause lung damage.

Cases of late pulmonary fibrosis, occurring up to 17 years after treatment have also been reported. In a long-term follow-up of 17 patients who survived childhood brain tumors eight (47%) died of lung fibrosis. Of these eight deaths, two occurred within 3years of treatment and 6 occurred 8-13 years after treatment. Of the patient who died,the median age at treatment was 2.5 years (range 1-12); the median age of the long survivors was 10 years (5-16 years at treatment). All five patients treated under the age of 5 years have died of pulmonary fibrosis. In this study the dose of Carmustine did not influence fatal outcome nor did co-administration of vincristine or spinal irradiation. Of the remaining survivors available for follow up, evidence of lung fibrosis was detected in all patients. The risk and benefit of Carmustine therapy mustbe carefully considered especially in young patients, due to extremely high risk of pulmonary toxicity.

Carmustine is carcinogenic in rats and mice, producing a marked increase in tumor incidence in doses approximately those employed clinically.
Bone marrow toxicity is a common and severe toxic effect of Carmustine. Complete blood count should be monitored frequently for at least six weeks after a dose. In addition to this, the liver, kidney and lung function should be examined and monitoredregularly during the carmustine therapy. Repeat doses of Carmustine should not to be given more frequently than every six weeks.

The bone marrow toxicity of Carmustine is cumulative and therefore the dosage adjustment must be considered on the basis of nadir blood counts from prior dose (see section 4.2).

This medicinal product contains 0.57 vol% ethanol (alcohol), it means 7.68 g perdose. This corresponds to 11.32 ml of beer or 4.72 ml wine per dose.

These amounts arise from a calculated example with 320 mg of carmustine (200 mg/m2 for 1.6 m2) dissolved in 9.6 ml (sterile dehydrated ethanol) and a volume of 1686 ml (see section 6.6).

For patients addicted to alcohol, this quantity can be harmful to health.

This must be considered in pregnant and breast-feeding women as well as in high-risk groups (patients with liver disease or epilepsy).

The alcohol content in this medicinal product may alter the effects of other drugs.

The alcohol content in this medicinal product may impair the ability to drive and the ability to use machines.

Effects on Driving

4.7    Effects on ability to drive and use machines
No studies have been undertaken on the consequences the medicine on the competency to drive and the ability to operate machines. However the possibility willhave to be taken into consideration, that the alcohol quantity in these pharmaceuticalmedicines can impair the competency to drive and the ability to operate machines.