Class: Antineoplastic Agents
VA Class: AN200
CAS Number: 9041-93-4
Brands: Blenoxane
Administer only under supervision of qualified clinicians experienced in use of cytotoxic therapy and only in a setting where adequate diagnostic and treatment facilities are readily available.121
Risk of developing pulmonary toxicity (e.g., pneumonitis, pulmonary fibrosis), particularly in geriatric patients >70 years of age and in patients receiving total bleomycin dosage >400 units.121 (See Pulmonary Toxicity under Cautions.)
Risk of severe idiosyncratic reaction (e.g., hypotension, mental confusion, fever, chills, wheezing) in patients with Hodgkin’s or non-Hodgkin’s disease.121 (See Sensitivity Reactions under Cautions.)
Introduction
Antineoplastic agent; mixture of basic cytotoxic glycopeptide antibiotics produced by Streptomyces verticillus (bleomycin A2 and bleomycin B2 are the major components).121
Uses for Bleomycin Sulfate
Hodgkin’s Disease
Treatment of Hodgkin’s disease.121 122 142 143 144 217
Combination therapy for induction of remissions is superior to single-drug therapy.142 143 144
Various combination regimens are used.142 143 144
Commonly used in combination with doxorubicin, vinblastine, and dacarbazine (ABVD regimen).121 122 142 143 144 217
Non-Hodgkin’s Disease
Has been used for treatment of non-Hodgkin’s lymphoma.121 122
Second- or third-generation combination regimens containing bleomycin no more effective than the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) for the treatment of advanced intermediate-grade or high-grade non-Hodgkin’s lymphoma.235 236 237 238 239
Testicular Cancer
Treatment of testicular embryonal cell carcinoma, choriocarcinoma, and teratocarcinoma.121 123 126 127 128 129 130 132 140
Combination chemotherapy with bleomycin, cisplatin, and etoposide is a regimen of choice for the treatment of advanced nonseminomatous testicular carcinoma.122 123 126 127 128 129 130 132
Combination chemotherapy with bleomycin, cisplatin, and etoposide is used for the treatment of disseminated seminoma testis.123 128 129 131 132 140
Pleural Effusions
Intracavitary injection as a sclerosing agent for intrapleural management and prevention of recurrent pleural effusions (pleurodesis) caused by metastatic tumors.121
At least as effective and possibly better tolerated than intrapleural tetracycline.121 147 148 149 151 154 155 156
Intrapleural talc may be preferred because of cost considerations.c d e f g
Has been used for intrapleural management of pneumothorax† associated with AIDS Pneumocystis jiroveci (Pneumocystis carinii) pneumonia.108 112
Head and Neck Cancer
Palliative treatment of squamous cell carcinomas of the head and neck (including mouth, tongue, tonsils, nasopharynx, oropharynx, sinuses, palate, lip, buccal mucosa, gingiva, epiglottis, larynx, skin).121
Poorer response to bleomycin in patients who have received prior radiation therapy for the treatment of head and neck cancer.121
Combination chemotherapy with cisplatin, methotrexate, and vincristine for advanced head and neck cancer.122 225
Cervical Cancer
Has been used for palliative treatment of squamous cell carcinoma of the cervix.121
Not considered a drug of choice for the treatment of advanced cervical cancer.232
Penile or Vulval Cancer
Palliative treatment of squamous cell carcinomas of the penis and vulva (in combination with other antineoplastic agents).121 234
AIDS-related Kaposi’s Sarcoma
Has been used for the palliative treatment of AIDS-related Kaposi’s sarcoma† (alone or in combination with doxorubicin, and a vinca alkaloid).122 146 172 173 174 175 176 177
Has been used as monotherapy for palliative treatment of early-stage disease.146 169 170 171
Bleomycin combination chemotherapy has been considered a regimen of choice for advanced disease,122 146 175 177 but a liposomal anthracycline currently considered first-line therapy.146 185
Ovarian Cancer
Has been used for the treatment of ovarian germ cell tumors† (in combination with cisplatin and etoposide).122 216
Intracranial Germ Cell Tumors
Has been used for the treatment of intracranial germ cell tumors† (in combination with cisplatin and vinblastine).122 178
Bleomycin Sulfate Dosage and Administration
General
Sensitivity Testing
Risk of anaphylactoid reactions in lymphoma patients (e.g., those with Hodgkin’s and non-Hodgkin’s disease).121
Administer 2 test doses (i.e., ≤2 units of bleomycin) before initiating full-dose therapy.121
After each test dose, monitor carefully for severe idiosyncratic reactions (see Boxed Warning).121 If no acute reaction occurs, recommended dosage regimen may then be administered.121
Take precautions to treat potential allergic reactions.121
Premedication
Administration
Administer by IV, IM, sub-Q, or intrapleural (intracavitary) injection.121
IV Administration
Administer by IV injection once or twice weekly.121
For solution and drug compatibility information, see Compatibility under Stability.
Reconstitution
Add a minimum of 5 or 10 mL of 0.9% sodium chloride injection to the vial labeled as containing 15 or 30 units, respectively, to provide a solution containing not more than 3 units/mL.121
Rate of Administration
Administer IV slowly over a 10-minute period.121
IM Administration
Administer by IM injection once or twice weekly.121
Reconstitution
Add 1–5 or 2–10 mL of sterile water for injection, 0.9% sodium chloride injection, or bacteriostatic water for injection to the vial containing 15 or 30 units, respectively, to provide solutions containing 3–15 units/mL.121
Sub-Q Administration
Administer by sub-Q injection once or twice weekly.121
Reconstitution
Add 1–5 or 2–10 mL of sterile water for injection, 0.9% sodium chloride injection, or bacteriostatic water for injection to the vial containing 15 or 30 units, respectively, to provide solutions containing 3–15 units/mL.121
Intrapleural Administration
Administer as a single bolus dose by intrapleural (intracavitary) injection through a thoracostomy tube.121
Drain pleural fluid via the thoracostomy by gravity or suction prior to instillation;102 103 104 110 118 119 120 121 confirmation of complete expansion of the lungs is recommended.121 148 153
Initiate therapy when chest tube drainage <100 mL in a 24 hour period or 100–300 mL in 24 hours under certain special circumstances.121
Reconstitution
Dissolve 60 units in 50–100 mL of 0.9% sodium chloride injection.121
Dosage
Available as bleomycin sulfate; dosage expressed in terms of bleomycin.121
Consult published protocols for the dosage of bleomycin and other chemotherapeutic agents and the method and sequence of administration.121
Adults
Hodgkin’s Disease
Increased sensitivity risk in lymphomas; administer test doses.121 (See Sensitivity Testing under Dosage and Administration.)
IV, IM, or Sub-Q
0.25–0.5 units/kg (10–20 units/m2) once or twice weekly.121
Following a 50% regression of tumor size, a maintenance dose of 1 unit daily or 5 units weekly can be given.121
Improvement unlikely to occur if not evident by week 2 of therapy.121
Non-Hodgkin’s Lymphoma
Increased sensitivity risk in lymphomas; administer test doses.121 (See Sensitivity Testing under Dosage and Administration.)
IV, IM, or Sub-Q
0.25–0.5 units/kg (10–20 units/m2) once or twice weekly.121
Testicular Cancer
IV, IM, or Sub-Q
0.25–0.5 units/kg (10–20 units/m2) once or twice weekly.121
Improvement in testicular cancer disease unlikely to occur if not evident by week 2 of therapy.121
Squamous Cell Carcinomas
IV, IM, or Sub-Q
0.25–0.5 units/kg (10–20 units/m2) once or twice weekly.121
Improvement in squamous cell carcinomas may not be evident for 3 weeks after initiation of therapy.121
Pleural Effusions
Intrapleural
50–60 units diluted and instilled into the chest through a thoracostomy tube followed by clamping of the tube, periodic rotation (optional)148 149 of the patient during the next 4 hours, and subsequent removal of the fluid.101 104 105 107 110 113 118 119 120 121
Length of time the chest tube remains in the pleural space after instillation of the drug should be individualized depending on the clinical status of the patient;121 allowing the chest tube to remain for at least 4 days after instillation may prevent pneumothorax.153
Dosage Modification for Toxicity
Contraindications to Continued Therapy121133
Pulmonary:
|
Clinical manifestations or radiologic evidence of pulmonary toxicity unless drug excluded as cause
|
Pulmonary diffusion capacity for carbon monoxide (DLco) <30–35% of the pretreatment value
|
Cardiovascular:
|
Intractable pain or ECG changes suggestive of pericarditis
|
Reduce Infusion Rate or Discontinue121133
Dermatologic:
|
Mucocutaneous toxicity (e.g., erythema, rash, striae, vesiculation, hyperpigmentation, and skin tenderness)
|
Pulmonary:
|
Rapid decline in forced vital capacity
|
Cardiovascular:
|
Acute chest pain syndrome suggestive of pleuropericarditis
|
Further courses of bleomycin therapy do not appear to be contraindicated, but careful evaluation of the patient must precede continuation of therapy.121
|
Prescribing Limits
Adults
IV, IM, or Sub-Q
Pulmonary toxicity: Administer cumulative dosages >400 units with great caution.121
When bleomycin is used in conjunction with other antineoplastic agents, pulmonary toxicity may occur at lower cumulative dosages of bleomycin.121
Intrapleural
Generally, maximum of 1 unit/kg or 40 units/m2 in geriatric patients.b
Special Populations
Renal Impairment
No dosage adjustment established by manufacturer for mild to moderate renal impairment; use with extreme caution in severe renal impairment.121
Cautions for Bleomycin Sulfate
Contraindications
Warnings/Precautions
Warnings
Patient Monitoring
Has a low therapeutic index; monitor patients carefully and frequently during and after therapy.121
Sensitivity Reactions
Severe Idiosyncratic Reactions
Potentially life-threatening, severe idiosyncratic (anaphylactoid) reactions (see Boxed Warning);121 may be immediate or delayed for several hours, and usually occurs after the first or second dose.121 Monitor carefully.121 (See Sensitivity Testing under Dosage and Administration.)
Treatment of anaphylactoid reactions is supportive and symptomatic and may include volume expansion, vasopressor therapy, antihistamines, and corticosteroids.121
Major Toxicities
Pulmonary Toxicity
Risk of dose- and age-related pulmonary toxicity (see Boxed Warning); use with extreme caution in compromised pulmonary function.121
Most severe toxicity.121
Pneumonitis can progress to potentially fatal pulmonary fibrosis.121
Most frequently with total dosages >400 units, but can occur with lower dosages.121
Risk may be increased with filgrastim or other cytokines.121
Dyspnea and fine rales are early manifestations.121
Perform chest radiographs every 1–2 weeks and sequential measurement of pulmonary diffusion capacity for carbon monoxide (DLco) monthly during therapy.121
Dosage modification or drug discontinuance may be necessary.121 (See Dosage Modification for Toxicity under Dosage and Administration.)
Cardiovascular Toxicity
Risk of pleuropericarditis and/or vascular toxicities (e.g., MI, cerebrovascular accident, thrombotic microangiography, cerebral arteritis).121
Sudden onset of acute chest pain may be first sign of pleuropericarditis.121
Dosage modification may be necessary in patients experiencing acute chest pain syndrome suggestive of pleuropericarditis.121 133
Raynaud's phenomenon, possibly due to bleomycin, combination therapy (e.g., vinblastine, cisplatin), underlying cancer or vascular compromise, or combination of factors.121 134 135 136 137
Dermatologic and Mucocutaneous Toxicity
Risk of developing dose-related adverse mucocutaneous effects (e.g., erythema, rash, striae, vesiculation, hyperpigmentation, skin tenderness, and less commonly hyperkeratosis, nail changes, alopecia, pruritus, stomatitis).121
Usually occurs during the second or third week of bleomycin therapy after a cumulative dose of 150–200 units.121
Most frequent toxicity, occurring in 50% of patients.121
Discontinuance of bleomycin may be necessary.121
Renal and Hepatic Toxicity
Begins as deterioration in renal or liver function tests; may occur anytime after bleomycin initiation.121
Febrile Reactions
Fever and chills are frequent, mainly with large single doses within a few hours of administration and persisting for 4–12 hours.b
General Precautions
Surgery
Sensitizes lung tissue to damaging effects of oxygen administered during surgery; lung damage can occur at Fl O2 concentrations that are usually considered safe.121
Maintain Fl O2 at concentrations approximating that of room air (25%) during surgery and the postoperative period and monitor carefully fluid replacement, focusing more on colloid administration rather than crystalloid.121
Intrapleural Risks
Rarely, pulmonary toxicity.121
Local pain.121
Hypotension, which may require treatment.121
Very rarely, death, but patients were very seriously ill prior to treatment.121
Specific Populations
Pregnancy
Category D.121
Lactation
Not known whether bleomycin is distributed into milk.121 Use not recommended.121
Pediatric Use
Safety and efficacy not established in pediatric patients.121
Geriatric Use
Greater risk of pulmonary toxicity in patients >70 years of age than in younger patients.240
Titrate dosage carefully.240
Renal Impairment
Use with extreme caution in patients with clinically important renal impairment.121
Common Adverse Effects
With IV administration, fever, chills, vomiting, and anorexia/weight loss (which may persist long after discontinuance of therapy).121 Mucocutaneous and dermatologic effects are most common and pulmonary toxicity is most serious.121 (See Major Toxicities under Cautions.)
With intracavitary administration into the pleural space, chest pain and fever.104 121 147 148 150 153 159 160 161 166
Interactions for Bleomycin Sulfate
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Antineoplastic agents
|
Increased risk of bleomycin-induced pulmonary toxicity121
|
Use with caution; pulmonary toxicity possible at lower total bleomycin dosages121
|
Filgrastim and other cytokines
|
Increased risk of bleomycin-induced pulmonary toxicity121
|
Use with caution; pulmonary toxicity possible at lower total bleomycin dosages121
|
Vitamins (e.g., vitamin C, riboflavin)
|
Bleomycin shown to be inactivated in vitro by ascorbic acid and riboflavin233
|
|
Bleomycin Sulfate Pharmacokinetics
Absorption
Not appreciably absorbed orally; must be administered parenterally for systemic effect.121
Following intrapleural administration, systemic absorption is about 45%.121 150 153
Onset
Improvement in Hodgkin’s disease or testicular cancer usually evident within 2 weeks.121
Improvement in squamous cell carcinoma usually evident within 3 weeks.121
Distribution
Extent
Distributed mainly into skin, lungs, kidneys, peritoneum, and lymphatics in animals.121
Concentrations higher in tumor cells of skin and lungs relative to hematopoietic tissue.b
Elimination
Metabolism
Metabolic fate not determined.b
Elimination Route
Excreted principally in urine (60–70%) as active drug.b
Half-life
Clcr>35 mL/minute: serum or plasma terminal half-life of about 2 hours.121
Clcr<35 mL/minute: terminal half-life inversely related to creatinine clearance.121
Special Populations
Moderately severe renal impairment (Clcr <35 mL/minute) decreases renal clearance; accumulation may occur with severe renal impairment.112 121
Stability
Storage
Parenteral
Powder for Injection
2–8°C; do not use after the expiration date is reached.121
Reconstituted Solutions
Use reconstituted solutions stored at room temperature within 24 hours.121 b
Although stable for 2 weeks at room temperature or 4 weeks at 2–8°C, reconstituted solutions contain no preservatives; discard within 24 hours of reconstitution.b
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Inactivated by agents containing sulfhydryl groups, hydrogen peroxide, and ascorbic acid.b
Forms Schiff base-type adducts with dextrose.106
Solution Compatibility
CompatibleHID 121
|
|---|
Sodium chloride 0.9%
|
Incompatible106 121
|
|---|
Dextrose 5% in water
|
Drug Compatibility
Admixture CompatibilityHID
Compatible
|
|---|
Amikacin sulfate
|
Dexamethasone sodium phosphate
|
Diphenhydramine HCl
|
Fluorouracil
|
Gentamicin sulfate
|
Heparin sodium
|
Hydrocortisone sodium phosphate
|
Streptomycin sulfate
|
Tobramycin sulfate
|
Vinblastine sulfate
|
Vincristine sulfate
|
Incompatible
|
|---|
Aminophylline
|
Ascorbic acid injection
|
Cefazolin sodium
|
Diazepam
|
Hydrocortisone sodium succinate
|
Methotrexate
|
Mitomycin
|
Nafcillin sodium
|
Penicillin G sodium
|
Terbutaline sulfate
|
Y-Site CompatibilityHID
Compatible
|
|---|
Allopurinol sodium
|
Amifostine
|
Aztreonam
|
Cefepime HCl
|
Cisplatin
|
Cyclophosphamide
|
Doxorubicin HCl
|
Doxorubicin HCl liposome injection
|
Droperidol
|
Etoposide phosphate
|
Filgrastim
|
Fludarabine phosphate
|
Fluorouracil
|
Gemcitabine HCl
|
Granisetron HCl
|
Heparin sodium
|
Leucovorin calcium
|
Melphalan HCl
|
Methotrexate sodium
|
Metoclopramide HCl
|
Mitomycin
|
Ondansetron HCl
|
Paclitaxel
|
Piperacillin sodium–tazobactam sodium
|
Sargramostim
|
Teniposide
|
Thiotepa
|
Vinblastine sulfate
|
Vincristine sulfate
|
Vinorelbine tartrate
|
ActionsActions
Antineoplastic antibiotic; active against gram-positive and gram-negative bacteria and fungi, but its cytotoxicity precludes its use as an anti-infective agent.b
Precise mechanism(s) of action not fully known but may involve inhibition of DNA synthesis and to a lesser extent inhibition of RNA and protein synthesis.121
Inhibits incorporation of thymidine into DNA.b
Exhibits no immunosuppressive activity.b
Advice to Patients
Advise patients about risk of pulmonary toxicity and to report any changes in pulmonary function (e.g., wheezing) to their clinician.b 121
Advise lymphoma patients of risk of severe idiosyncratic reactions (hypotension, mental confusion, fever, chills, wheezing).121
Advise patients to report any sudden onset of chest pain to their clinician.b 121
Advise patients of dermatologic and mucocutaneous effects and that they may not be apparent for several weeks after 100–200 units have been given.b 121
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.121
Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.121
Importance of informing patients of other important precautionary information.121 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Bleomycin Sulfate
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Parenteral
|
For injection
|
15 units (of bleomycin)*
|
Blenoxane
|
Bristol-Myers Squibb
|
|
|
|
Bleomycin Sulfate for Injection
|
Bedford, Mayne, Sicor
|
|
|
30 units (of bleomycin)*
|
Blenoxane
|
Bristol-Myers Squibb
|
|
|
|
Bleomycin Sulfate for Injection
|
Bedford, Mayne, Sicor
|
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
Only references cited for selected revisions after 1984 are available electronically.
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136. Adoue D, Arlet P. Bleomycin and Raynaud’s phenomenon. Ann Intern Med. 1984; 100:770. [IDIS 184382] [PubMed 6201095]
137. Doll DC, List AF, Greco FA et al. Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumors of the testis. Ann Intern Med. 1986; 105:48-51. [IDIS 217843] [PubMed 2424354]
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140. Loehrer PJ, Birch R, Williams SD et al. Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience. J Clin Oncol. 1987; 5:1212-20. [PubMed 2442317]
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