Pronunciation: BLEE-oh-MYE-sin SUL-fate
Class: Antineoplastic, Antibiotic
- Injection, lyophilized powder for solution 15 units (15 units = 15 mg)
- Injection, lyophilized powder for solution 30 units (30 units = 30 mg)
Bleomycin is a mixture of cytotoxic glycopeptide antibiotics. It inhibits DNA synthesis. When administered intrapleurally, bleomycin acts as a sclerosing agent.
Rapidly absorbed. T max is 30 to 60 min. Bioavailability is 100% and 70% following IM and subcutaneous administration, respectively, and 45% following intraperitoneal and intrapleural administration.
Mean Vd is 17.5 L/m 2 . Widely distributed throughout the body.
The half-life is approximately 2 h; 65% and 40% is excreted in urine as active bleomycin after IV and intrapleural administration, respectively.
Special PopulationsRenal Function Impairment
In those with CrCl less than 35 mL/min, the half-life increases.Hepatic Function Impairment
Pharmacokinetics have not been evaluated.Elderly
Pharmacokinetics have not been evaluated.Children
Children younger than 3 yr of age have a higher total body Cl than adults.
Indications and Usage
Palliative treatment for Hodgkin disease and non-Hodgkin lymphoma; as palliative treatment for testicular carcinoma (eg, embryonal cell, choriocarcinoma, teratocarcinoma); sclerosis of malignant pleural effusions (eg, treatment, prevention); as palliative treatment for squamous cell carcinomas (eg, head, neck, penis, cervix, vulva).
Malignant pericardial effusion; malignant peritoneal effusion; warts (intralesional); mycosis fungoides; osteosarcoma; AIDS-related Kaposi sarcoma.
None well documented.
Dosage and AdministrationHodgkin Disease
IV / IM / Subcutaneous 2 units or less for the first 2 doses. If no acute reaction occurs, follow the regular dosage schedule of 10 to 20 units/m 2 1 or 2 times/wk. After a 50% regression of tumor size, a maintenance dose of 1 unit/day or 5 units/wk can be given IV or IM.Non-Hodgkin Lymphoma
IV / IM / Subcutaneous 2 units or less for the first 2 doses. If no acute reaction occurs, follow the regular dosage schedule of 10 to 20 units/m 2 1 or 2 times/wk.Malignant Pleural Effusions
Thoracostomy tube 60 units as a single-bolus dose intrapleural injection.Squamous Cell Carcinoma, Testicular Carcinoma
IV / IM / Subcutaneous 10 to 20 units/m 2 1 or 2 times/wk.Renal Function Impairment
CrCl 40 to 50 mL/min, administer 70% of dose. CrCl 30 to 40 mL/min, administer 60% of dose. CrCl 20 to 30 mL/min, administer 55% of dose. CrCl 10 to 20 mL/min, administer 45% of dose. CrCl 5 to 10 mL/min, administer 40% of dose.
- Pulmonary toxicity of bleomycin appears to be dose-related, with a striking increase when the total dose is more than 400 units. Total doses of more than 400 units should be given with great caution.
- Diligently follow institutional and National Institutes of Health procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering bleomycin. Avoid exposure by direct contact of the skin, mucous membranes, and eyes.
- If accidental skin or mucous membrane contact occurs, wash thoroughly with soap and water. If accidental eye contact occurs, immediately institute standard irrigation techniques.
- Do not reconstitute or dilute bleomycin with dextrose 5% in water or any other dextrose-containing diluent. Loss of bleomycin potency will occur.
- For subcutaneous or IM administration, reconstitute powder for injection with sterile water for injection, sodium chloride 0.9% injection, or bacteriostatic water for injection. Reconstitute 15-unit vial with 1 to 5 mL of diluent; reconstitute 30-unit vial with 2 to 10 mL of diluent.
- For IV administration, reconstitute powder for injection with sodium chloride 0.9% injection. Reconstitute 15-unit vial with 5 mL of diluent; reconstitute 30-unit vial with 10 mL of diluent. Infuse prescribed dose slowly over 10 min.
- For intrapleural administration, dissolve 60 units of bleomycin in 50 to 100 mL of sodium chloride 0.9% injection. Clamp thoracostomy tube after instilling bleomycin. Move patient from supine to left and right lateral positions several times over next 4 h, then remove clamp and reestablish suction.
- Do not administer if particulate matter or cloudiness is noted.
- When bleomycin is used in combination with other antineoplastic agents, pulmonary toxicities may occur at lower doses.
- Improvement of Hodgkin disease and testicular tumors is prompt and noted within 2 wk. If no improvement is seen by this time, improvement is unlikely. Squamous cell cancers respond more slowly, sometimes requiring as long as 3 wk before any improvement is noted.
Store powder for injection at 36° to 46°F. Bleomycin is stable for 24 h at room temperature when reconstituted with sodium chloride 0.9% injection.
Elimination of bleomycin may be decreased secondary to cisplatin-induced renal dysfunction, increasing the risk of bleomycin toxicity. Use with caution. Monitor renal function and adjust the bleomycin dose as needed.Digoxin, hydantoins (eg, phenytoin)
Bleomycin may decrease serum concentrations of digoxin and hydantoins. Monitor phenytoin plasma levels and adjust the phenytoin dosage appropriately. IV phenytoin may be useful.Oxygen
Risk for pulmonary toxicity is increased. Preventive measures include maintaining the inspired oxygen fraction at concentrations approximating those of room air (25%) during surgery and the postoperative period and carefully monitoring fluid replacement, focusing more on colloid administration rather than crystalloid.
Hypotension; cerebral arteritis, cerebrovascular accidents, MI, Raynaud phenomenon, thrombotic microangiopathy (with combination chemotherapy).
Alopecia, erythema, hyperkeratosis, hyperpigmentation, nail changes, pruritus, rash, skin tenderness, stomatitis, striae, vesiculation (approximately 50%); scleroderma-like skin changes (postmarketing).
Pain, pain at tumor site, phlebitis.
Dyspnea, pneumonitis, pulmonary fibrosis, rales.
Idiosyncratic reaction including chills, fever, hypotension, mental confusion, and wheezing (about 1% of lymphoma patients); acute chest pain, chills, fever.
It is recommended that bleomycin be administered under the supervision of a qualified health care provider experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Pulmonary fibrosis is the most severe toxicity associated with bleomycin. The most frequent presentation is pneumonitis occasionally progressing to pulmonary fibrosis. Its occurrence is higher in elderly patients and in those receiving more than 400 units total dose, but pulmonary toxicity has been observed in young patients and those treated with low doses.
A severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing has been reported in approximately 1% of lymphoma patients treated with bleomycin.
Monitor patients carefully and frequently for pulmonary toxicity and hypersensitivity reactions during and after therapy. Monitor renal function during administration in patients with CrCl less than 50 mL/min. Monitor patient for extravasation during therapy.
Ensure chest x-rays are obtained and evaluated every 1 to 2 wk during therapy to monitor for onset of pulmonary toxicity. If changes are noted, ensure that therapy is discontinued until it is determined if changes are drug-related.
Ensure diffusion capacity for carbon monoxide (DL co ) is determined before starting therapy and then monthly during treatment. Ensure that therapy is discontinued if DL co falls below 30% to 35% of pretreatment value.
Category D .
Safety and efficacy not established.
Pulmonary toxicity was more common in patients older than 70 yr of age. Take care with dose selection.
Has occurred, usually after the first or second dose.
Use extreme caution. Dosage adjustment required in patients with CrCl 50 mL/min or less.
Special Risk Patients
Use with extreme caution in patients with compromised pulmonary function.
Local irritation or phlebitis may occur. Refer to your institution-specific protocol.
Hepatic toxicity has occurred infrequently. This toxicity may occur at any time.
Skin toxicity, a relatively late manifestation, appears to be related to the cumulative dose. It usually develops in the second and third week of treatment after administration of 150 to 200 units of the drug.
If patient is to undergo surgical intervention, ensure that surgical team (including anesthesiologist) is aware of treatment with bleomycin and that FIO 2 should be maintained, if possible, at concentrations no more than 25%. Fluid replacement should consist of colloids rather than crystalloids to reduce the risk of lung damage.
- Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
- Advise patient that medication may be used in combination with other agents to achieve max benefit possible.
- Inform patients that antibiotics, including bleomycin, should only be used to treat bacterial infections. They do not treat viral infections (eg, the common cold).
- Advise patient that medication may cause hair loss but that this is reversible when therapy is stopped.
- Advise patient to immediately report any of the following to health care provider: rash; hives; difficulty breathing or unexplained shortness of breath; chest pain; fever, chills, or other signs of infection; sores in mouth; pain, redness, or swelling at injection site.
- Advise patient to report any of the following to health care provider: persistent nausea, vomiting, or appetite loss; persistent or worsening general body weakness; skin changes; nail changes.
- Caution women of childbearing potential to avoid becoming pregnant during therapy.
- Advise breast-feeding women not to breast-feed during therapy.
- Advise patient that frequent follow-up visits, laboratory tests, x-rays, and breathing tests will be required to monitor therapy, and to keep appointments.
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