⚠️ Warnings
Regular pulmonary function tests must be performed in patients treated with bleomycin, as well as weekly chest X-rays. Monitoring should continue for up to 4 weeks after the end of treatment, and patients should be under clinical supervision for approximately 8 weeks.
With concurrent thoracic radiotherapy, pulmonary function tests and chest X-rays should be performed more frequently as appropriate. Pulmonary function tests, particularly measurement of carbon monoxide diffusion capacity and vital capacity, often allow early diagnosis of pulmonary toxicity.
If unexplained cough, dyspnoea, or basal crepitations occur, or if diffuse reticular markings appear on chest X-ray, bleomycin administration must be immediately discontinued until bleomycin toxicity has been excluded as a possible cause. Administration of antibiotics and, if necessary, corticosteroids (e.g. intramuscular hydrocortisone sodium succinate 100 mg daily for 5 days, followed by prednisolone 10 mg twice daily) is recommended.
In cases of pulmonary damage due to bleomycin administration, bleomycin must never be administered again (see section 4.3).
Pulmonary toxicity of bleomycin appears to be dose-dependent, with a dramatic increase at total doses above 400 × 10³ IU. Total doses above 400 × 10³ IU should be administered with great caution.
Although bleomycin pulmonary toxicity clearly increases at total doses of 400 × 10³ IU, it may also occur at considerably lower doses, particularly in elderly patients, patients with impaired hepatic or renal function, patients with pre-existing pulmonary disease, patients with prior pulmonary irradiation, and patients receiving oxygen. In these cases, a risk factor for pulmonary toxicity is present.
Pulmonary function tests with 100% oxygen should not be performed in patients who have been treated with bleomycin. Pulmonary function tests with 21% oxygen are recommended.
Due to the effect of bleomycin on lung tissue, patients who have received this medicinal product are at increased risk of developing pulmonary toxicity when oxygen is administered during surgery. Prolonged exposure to very high oxygen concentrations is a known cause of lung damage; however, after bleomycin administration, lung damage may occur at oxygen concentrations lower than those usually considered safe. Optimal surgical management therefore requires administration of the lowest inspired oxygen fraction (FiO₂) compatible with adequate oxygenation (see section 4.8).
Bleomycin must be administered with maximum caution in patients with lung carcinoma, as these patients have an increased incidence of pulmonary toxicity.
Sensitivity to bleomycin increases in elderly individuals.
Pulmonary toxicity has occasionally been observed in younger patients receiving low doses.
Because two-thirds of the administered dose of bleomycin is excreted unchanged in the urine, the rate of elimination is greatly influenced by renal function.
Plasma concentrations increase significantly when standard doses are administered to patients with renal impairment.
This medicinal product should not be administered to pregnant patients or breast-feeding women. Animal studies have shown that bleomycin, like most cytostatic medicinal products, may have teratogenic and mutagenic properties. Therefore, patients of both sexes should use effective contraception for up to six months after the end of treatment (see section 4.6).
As with other cytotoxic medicinal products, bleomycin may induce tumour lysis syndrome in patients with rapidly growing tumours. Appropriate supportive care and pharmacological measures may prevent or mitigate these complications.
Acute myeloid leukaemia and myelodysplastic syndrome have been reported in patients treated concomitantly with bleomycin and other cytostatic agents.
