In approximately 1% of the lymphoma patients treated with bleomycin, an idiosyncratic reaction, similar to anaphylaxis clinically, has been reported. The reaction may be immediate or delayed for several hours, and usually occurs after the first or second dose (see WARNINGS). It consists of hypotension, mental confusion, fever, chills, and wheezing. Treatment is symptomatic including volume expansion, pressor agents, antihistamines, and corticosteroids.
These adverse reactions have been reported in approximately 50% of treated patients. They consist of erythema, rash, striae, vesiculation, hyperpigmentation, and tenderness of the skin. Hyperkeratosis, nail changes, alopecia, pruritus, and stomatitis have also been reported. It was necessary to discontinue bleomycin therapy in 2% of treated patients because of these toxicities.
Scleroderma-like skin changes have been reported.
Skin toxicity is a relatively late manifestation usually developing in the second and third week of treatment after 150 to 200 units of bleomycin have been administered and appears to be related to the cumulative dose.
Intrapleural administration of bleomycin has been associated with local pain. Hypotension possibly requiring symptomatic treatment has been reported. Death has been reported in association with bleomycin pleurodesis in seriously ill patients.
Vascular toxicities coincident with the use of bleomycin in combination with other antineoplastic agents have been reported. The events are clinically heterogeneous and may include myocardial infarction, cerebrovascular accident, thrombotic microangiopathy (HUS), or cerebral arteritis. Various mechanisms have been proposed for these vascular complications. There are also reports of Raynaud’s phenomenon occurring in patients treated with bleomycin in combination with vinblastine with or without cisplatin or, in a few cases, with bleomycin as a single agent. It is currently unknown if the cause of Raynaud’s phenomenon in these cases is the disease, underlying vascular compromise, bleomycin, vinblastine, hypomagnesemia, or a combination of any of these factors.
Fever, chills, and vomiting have been reported. Anorexia and weight loss have been reported and may persist long after termination of this medication. Pain at tumor site, phlebitis, and other local reactions have been reported.
Malaise has been reported.
Because of the possibility of an anaphylactoid reaction, lymphoma patients should be treated with 2 units or less for the first 2 doses. If no acute reaction occurs, then the regular dosage schedule may be followed.
The following dose schedule is recommended:
Squamous cell carcinoma, non-Hodgkin’s lymphoma, testicular carcinoma– 0.25 to
0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly.
Hodgkin’s Disease – 0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. After a 50% response, a maintenance dose of 1 unit daily or 5 units weekly intravenously or intramuscularly should be given.
Pulmonary toxicity of Bleomycin for Injection, USP appears to be dose-related with a striking increase when the total dose is over 400 units. Total doses over 400 units should be given with great caution.
Note: When Bleomycin for Injection, USP is used in combination with other antineoplastic agents, pulmonary toxicities may occur at lower doses.
Improvement of Hodgkin’s disease and testicular tumors is prompt and noted within 2 weeks. If no improvement is seen by this time, improvement is unlikely. Squamous cell cancers respond more slowly, sometimes requiring as long as 3 weeks before any improvement is noted.
Use in Patients with Renal Insufficiency
The following dosing reductions are proposed for patients with creatinine clearance (CrCL) values of less than 50 mL/min:
for Injection, USP
50 and above
40 to 50
30 to 40
20 to 30
10 to 20
5 to 10
CrCL can be estimated from the individual patient’s measured serum creatinine (Scr) values using the Cockcroft and Gault formula:
Males CrCL = [weight x (140 – Age)]/(72 x Scr)
Females CrCL = 0.85 x [weight x (140 – Age)]/(72 x Scr)
Where CrCL in mL/min/1.73m2 , weight in kg, age in years, and Scr in mg/dL.
Bleomycin for Injection may be given by the intramuscular, intravenous, subcutaneous, or intrapleural routes.
Caution should be exercised when handling Bleomycin for Injection. Procedures for proper handling and disposal of anticancer drugs should be utilized. Several guidelines on this subject have been published.1-4 To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing Bleomycin for Injection. If Bleomycin for Injection contacts the skin, immediately wash the skin thoroughly with soap and water. If contact with mucous membranes occurs, the membranes should be flushed immediately and thoroughly with water. More information is available in the references listed below.
The Bleomycin for Injection 15 units vial should be reconstituted with 1 to 5 mL of Sterile Water for Injection, USP, Sodium Chloride for Injection, 0.9%, USP, or Sterile Bacteriostatic Water for Injection, USP. The Bleomycin for Injection 30 units vial should be reconstituted with 2 to 10 mL of the above diluents.
The contents of the 15 units or 30 units vial should be dissolved in 5 mL or 10 mL, respectively, of Sodium Chloride for Injection, 0.9%, USP, and administered slowly over a period of 10 minutes.
Sixty units of Bleomycin for Injection are dissolved in 50 to 100 mL Sodium Chloride for Injection, 0.9%,USP, and administered through a thoracostomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The literature suggests that successful pleurodesis is, in part, dependent upon complete drainage of the pleural fluid and re-establishment of negative intrapleural pressure prior to instillation of a sclerosing agent. Therefore, the amount of drainage from the chest tube should be as minimal as possible prior to instillation of Bleomycin for Injection. Although there is no conclusive evidence to support this contention, it is generally accepted that chest tube drainage should be less than 100 mL in a 24-hour period prior to sclerosis. However, Bleomycin for Injection instillation may be appropriate when drainage is between 100 to 300 mL under clinical conditions that necessitate sclerosis therapy. The thoracostomy tube is clamped after Bleomycin for Injection instillation. The patient is moved from the supine to the left and right lateral positions several times during the next four hours. The clamp is then removed and suction re-established. The amount of time the chest tube remains in place following sclerosis is dictated by the clinical situation.
The intrapleural injection of topical anesthetics or systemic narcotic analgesia is generally not required.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.