Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
If bleomycin is used as part of combination chemotherapy, its toxicity should be taken into account when selecting and dosing other agents with a similar spectrum of toxicity.

Careful case-specific assessment of the risks and benefits is required before any planned concomitant or sequential use of other agents or treatments that may increase the likelihood or severity of toxicity (as a result of pharmacodynamic or pharmacokinetic interactions). Patients treated with such combinations must be closely monitored for signs of toxicity to allow for early intervention.

An increased risk of pulmonary toxicity has been reported with concomitant use of BCNU, mitomycin, cyclophosphamide, methotrexate and gemcitabine.
Prior or concurrent thoracic radiotherapy contributes significantly to an increase in the frequency and severity of pulmonary toxicity.

Because of the potential of bleomycin to sensitize lung tissue, pulmonary toxicity increases when bleomycin is administered during surgical procedures requiring increased oxygen supplementation. The inspiratory O2 concentration must therefore be reduced both intra- and postoperatively.

Raynaud like phenomena ranging from acral ischemia to necrosis of distal parts of the body (fingers, toes, tip of the nose) have been reported in patients with testicular cancer treated with a combination of bleomycin and vinca alkaloids.


A positive correlation between GFR (glomerular filtration rate) and lung function was observed in patients receiving combination therapy with cisplatin, vinblastine and bleomycin. Bleomycin should therefore be used with caution in patients with severe renal impairment. In another study, increasing doses of cisplatin were shown to be associated with a decrease in creatinine clearance and thus in the elimination of bleomycin.

Combination therapy with cisplatin in particular increases the pulmonary toxicity of bleomycin.
Particular caution is therefore required with this combination. Data from the literature suggest that cisplatin should be administered after bleomycin.

An increase in the number of neutrophils and stimulation of the ability to produce oxygen free radicals after administration of granulocyte colony- stimulating factor may promote lung injury.
The rate and amount of absorption of oral acetyldigoxin and phenytoin may be decreased during treatment with bleomycin.

The bacteriostatic efficacy of gentamycin, amikacin and ticarcillin may be reduced.

Administration of live vaccines may result in severe to life-threatening infections in patients whose immune systems are compromised by chemotherapeutic agents, including bleomycin. Vaccination with live vaccines should be avoided in patients receiving bleomycin.