Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Patients receiving chemotherapy with bleomycin should be closely monitored by experienced oncologists.
A particularly strict benefit/risk assessment is required after pulmonary or mediastinal radiotherapy.
In case of renal impairment, bleomycin should only be used with particular caution and at a reduced dose.
Due to possible mutagenic effects of bleomycin on male and female germ cells, reliable contraception must be used during and for 6 months after the end of treatment.


Pulmonary reactions
Patients receiving treatment with bleomycin should be closely monitored for any signs of pulmonary dysfunction.
Pulmonary reactions are the most serious side effects and occur in approximately 10 % of treated patients either during or after the end of a treatment cycle. The most common form is interstitial lung disease. If not recognized and treated immediately, this can progress to pulmonary fibrosis. Approximately 1 % of treated patients die as a result of pulmonary fibrosis.
Regular chest X-rays (preferably weekly) and lung function tests are recommended and should continue for 4 weeks after completion of a treatment cycle.
Pulmonary toxicity is both dose- and age- dependent; it is more common in patients over 70 years of age and those receiving a total dose greater than 400 units. It is significantly increased by thoracic radiotherapy and by hyperoxia during anesthesia for surgical procedures.
Pulmonary toxicity has also been observed occasionally in young patients receiving low doses.
Vascular changes occur in the lungs that lead to partial destruction of elastic components of the vessel wall. The earliest symptoms of bleomycin- induced lung injury are dyspnea and fine crackles. If pulmonary changes are noted, treatment must be discontinued until it is determined whether they are due to bleomycin. Patients should be given broad- spectrum antibiotics and corticosteroids.
Bleomycin sensitivity increases in older age.
If shortness of breath or pulmonary infiltrates occur that cannot be unequivocally attributed to the malignancy or concomitant pulmonary disease, bleomycin should be discontinued immediately and the patient treated with a corticosteroid and broad-spectrum antibiotics.

Although pulmonary toxicity of bleomycin appears to occur in a dose-dependent manner when the total dose exceeds 400 units (equivalent to approximately 225 units/m2 BSA) it may also be observed at lower doses, particularly in elderly patients, patients with impaired renal function, preexisting pulmonary disease, previous thoracic radiotherapy and patients requiring oxygen therapy.
Fever and chills
Like most cytotoxic agents, bleomycin can cause immediate or delayed toxicity. Fever on the day of injection is the most common immediate reaction.
Fever and chills are common. These sometimes occur 2-6 hours after the first injection. In cases of persistent high fever, administration of antipyretics may be required. The frequency of febrile episodes decreases with further injections.


Skin and mucous membranes
If cutaneous adverse reactions occur in AIDS patients, treatment should be discontinued and not resumed.
Induration, edema, hyperkeratosis, nail changes, formation of blisters on skin areas where there is prolonged pressure, e.g., the elbows, hair loss and stomatitis may also occur. These side effects are rarely serious and usually resolve after discontinuation of treatment.
Using bleomycin in combination with radiotherapy or other medications associated with mucosal damage appears to worsen stomatitis. Skin toxicity occurs relatively late and is correlated with the total dose; it usually develops in the second and third week after administration of 150 to 200 units (USP) of bleomycin.


Idiosyncratic reactions
An idiosyncratic reaction clinically similar to anaphylaxis has been reported in approximately 1% of patients treated with bleomycin for lymphoma. The reaction may occur immediately or after several hours, usually after the first or second dose. It manifests as hypotension, confusion, fever, chills, wheezing and stridor. Treatment is symptomatic and includes fluid replacement, vasopressors antihistamines and corticosteroids.


Hypersensitivity
Because of the possibility of an anaphylactoid reaction (in 1 % of patients with lymphoma, according to the literature), patients should start with a test dose of 1-2 units (USP). If no acute reaction occurs the regular dosage regimen can be administered.


Gastrointestinal tract
Gastrointestinal adverse reactions such as nausea and vomiting rare possible, but are more commonly observed with high-dose regimens. Antiemetics may be helpful. Loss of appetite and weight loss are common and may persist for an extended period beyond the end of treatment.


Blood and lymphatic system disorders
Acute myeloid leukaemia and myelodysplastic syndrome have been reported in patients who have received concomitant treatment with bleomycin and other antineoplastic agents.


Other
Vascular toxicity has been reported with the use of bleomycin, particularly in combination with other antineoplastic agents. Events are clinically inconsistent and include myocardial infarction, stroke, thrombotic microangiopathies such as hemolytic uremic syndrome and cerebral vasculitis. Like other cytotoxic agents, bleomycin can cause tumor lysis syndrome in patients with rapidly growing tumors. Appropriate supportive treatment and pharmacological measures may be able to prevent or mitigate such complications.
Pediatric population
Insufficient data are available on the use of bleomycin in children and adolescents. Until more information is available, bleomycin should only be administered to this patient group in exceptional cases and at dedicated centers. If its use is indicated, the individual doses specified in relation to BSA should be administered.
No studies have been conducted by Baxter Healthcare Corporation in children and adolescents.

Effects on Driving

4.7 Effects on ability to drive and use machines
Possible undesirable effects of chemotherapy with bleomycin, such as nausea and vomiting, may indirectly affect the patient's ability to drive and use machines.