⚠️ Warnings
Patients treated with bleomycin require regular monitoring of pulmonary function, as well as weekly chest X-ray examinations. Monitoring should continue for up to 4 weeks after completion of treatment, and patients should be under clinical supervision for approximately 8 weeks.
In the case of 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 diffusing capacity and vital capacity, often allow early diagnosis of pulmonary toxicity.
If unexplained cough, dyspnoea, or basal crepitations occur, or if a chest X-ray shows diffuse reticular shadowing, bleomycin administration must be immediately discontinued until bleomycin toxicity is excluded as a possible cause. Administration of antibiotics is recommended and, if necessary, corticosteroids (for example, hydrocortisone sodium succinate 100 mg intramuscularly daily for 5 days, followed by prednisolone 10 mg twice daily).
In the event of pulmonary damage due to bleomycin administration, bleomycin must never be administered again (see section 4.3).
The pulmonary toxicity of bleomycin appears to be dose-dependent, with a dramatic increase at total doses exceeding 400 × 10³ IU. Total doses above 400 × 10³ IU should be administered with great caution.
Although pulmonary toxicity of bleomycin clearly increases at a total dose 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, after previous lung irradiation, and in 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 pulmonary 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, following 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 sections 4.8).
Bleomycin must be administered with utmost caution in patients with lung carcinoma, as these patients have an increased incidence of pulmonary toxicity.
Sensitivity to bleomycin increases in elderly persons.
Pulmonary toxicity has occasionally been observed in younger patients receiving low doses.
Since two-thirds of the administered dose of bleomycin is excreted unchanged in the urine, the rate of excretion 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 completion of treatment (see section 4.6).
As with other cytotoxic substances, bleomycin may induce tumour lysis syndrome in patients with rapidly growing tumours. Appropriate supportive care and pharmacological measures can prevent or mitigate these complications.
Acute myeloid leukaemia and myelodysplastic syndrome have been reported in patients who were concomitantly treated with bleomycin and other cytostatic agents.
