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Bleomycin

Class: Antineoplastic Agents
VA Class: AN200
CAS Number: 9041-93-4
Brands: Blenoxane

Medically reviewed by Drugs.com on Jul 22, 2021. Written by ASHP.

Warning

  • 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.

  • 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. (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. (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).

Uses for Bleomycin

Hodgkin’s Disease

Treatment of Hodgkin’s disease.

Combination therapy for induction of remissions is superior to single-drug therapy.

Various combination regimens are used.

Commonly used in combination with doxorubicin, vinblastine, and dacarbazine (ABVD regimen).

Non-Hodgkin’s Disease

Has been used for treatment of non-Hodgkin’s lymphoma.

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.

Testicular Cancer

Treatment of testicular embryonal cell carcinoma, choriocarcinoma, and teratocarcinoma.

Combination chemotherapy with bleomycin, cisplatin, and etoposide is a regimen of choice for the treatment of advanced nonseminomatous testicular carcinoma.

Combination chemotherapy with bleomycin, cisplatin, and etoposide is used for the treatment of disseminated seminoma testis.

Pleural Effusions

Intracavitary injection as a sclerosing agent for intrapleural management and prevention of recurrent pleural effusions (pleurodesis) caused by metastatic tumors.

At least as effective and possibly better tolerated than intrapleural tetracycline.

Intrapleural talc may be preferred because of cost considerations.

Has been used for intrapleural management of pneumothorax associated with AIDS Pneumocystis jiroveci (Pneumocystis carinii) pneumonia.

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).

Poorer response to bleomycin in patients who have received prior radiation therapy for the treatment of head and neck cancer.

Combination chemotherapy with cisplatin, methotrexate, and vincristine for advanced head and neck cancer.

Cervical Cancer

Has been used for palliative treatment of squamous cell carcinoma of the cervix.

Not considered a drug of choice for the treatment of advanced cervical cancer.

Penile or Vulval Cancer

Palliative treatment of squamous cell carcinomas of the penis and vulva (in combination with other antineoplastic agents).

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).

Has been used as monotherapy for palliative treatment of early-stage disease.

Bleomycin combination chemotherapy has been considered a regimen of choice for advanced disease, but a liposomal anthracycline currently considered first-line therapy.

Ovarian Cancer

Has been used for the treatment of ovarian germ cell tumors (in combination with cisplatin and etoposide).

Intracranial Germ Cell Tumors

Has been used for the treatment of intracranial germ cell tumors (in combination with cisplatin and vinblastine).

Bleomycin Dosage and Administration

General

  • Individualize dosage carefully according to individual requirements and response.

  • Consult specialized references for procedures for proper handling and disposal of antineoplastics.

Sensitivity Testing

  • Risk of anaphylactoid reactions in lymphoma patients (e.g., those with Hodgkin’s and non-Hodgkin’s disease).

  • Administer 2 test doses (i.e., ≤2 units of bleomycin) before initiating full-dose therapy.

  • After each test dose, monitor carefully for severe idiosyncratic reactions (see Boxed Warning). If no acute reaction occurs, recommended dosage regimen may then be administered.

  • Take precautions to treat potential allergic reactions.

Premedication

  • Intrapleural injection of local anesthetics or systemic administration of opiates prior to the intrapleural procedure may relieve pain associated with pleurodesis but generally are not considered necessary.

Administration

Administer by IV, IM, sub-Q, or intrapleural (intracavitary) injection.

IV Administration

Administer by IV injection once or twice weekly.

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.

Rate of Administration

Administer IV slowly over a 10-minute period.

IM Administration

Administer by IM injection once or twice weekly.

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.

Sub-Q Administration

Administer by sub-Q injection once or twice weekly.

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.

Intrapleural Administration

Administer as a single bolus dose by intrapleural (intracavitary) injection through a thoracostomy tube.

Drain pleural fluid via the thoracostomy by gravity or suction prior to instillation; confirmation of complete expansion of the lungs is recommended.

Initiate therapy when chest tube drainage <100 mL in a 24 hour period or 100–300 mL in 24 hours under certain special circumstances.

Reconstitution

Dissolve 60 units in 50–100 mL of 0.9% sodium chloride injection.

Dosage

Available as bleomycin sulfate; dosage expressed in terms of bleomycin.

Consult published protocols for the dosage of bleomycin and other chemotherapeutic agents and the method and sequence of administration.

Adults

Hodgkin’s Disease

Increased sensitivity risk in lymphomas; administer test doses. (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.

Following a 50% regression of tumor size, a maintenance dose of 1 unit daily or 5 units weekly can be given.

Improvement unlikely to occur if not evident by week 2 of therapy.

Non-Hodgkin’s Lymphoma

Increased sensitivity risk in lymphomas; administer test doses. (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.

Testicular Cancer
IV, IM, or Sub-Q

0.25–0.5 units/kg (10–20 units/m2) once or twice weekly.

Improvement in testicular cancer disease unlikely to occur if not evident by week 2 of therapy.

Squamous Cell Carcinomas
IV, IM, or Sub-Q

0.25–0.5 units/kg (10–20 units/m2) once or twice weekly.

Improvement in squamous cell carcinomas may not be evident for 3 weeks after initiation of therapy.

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) of the patient during the next 4 hours, and subsequent removal of the fluid.

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; allowing the chest tube to remain for at least 4 days after instillation may prevent pneumothorax.

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.

Prescribing Limits

Adults

IV, IM, or Sub-Q

Pulmonary toxicity: Administer cumulative dosages >400 units with great caution.

When bleomycin is used in conjunction with other antineoplastic agents, pulmonary toxicity may occur at lower cumulative dosages of bleomycin.

Intrapleural

Generally, maximum of 1 unit/kg or 40 units/m2 in geriatric patients.

Special Populations

Renal Impairment

No dosage adjustment established by manufacturer for mild to moderate renal impairment; use with extreme caution in severe renal impairment.

Cautions for Bleomycin

Contraindications

  • Known hypersensitivity or idiosyncrasy to bleomycin or any ingredient in the formulation.

Warnings/Precautions

Warnings

Patient Monitoring

Has a low therapeutic index; monitor patients carefully and frequently during and after therapy.

Sensitivity Reactions

Severe Idiosyncratic Reactions

Potentially life-threatening, severe idiosyncratic (anaphylactoid) reactions (see Boxed Warning); may be immediate or delayed for several hours, and usually occurs after the first or second dose. Monitor carefully. (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.

Major Toxicities

Pulmonary Toxicity

Risk of dose- and age-related pulmonary toxicity (see Boxed Warning); use with extreme caution in compromised pulmonary function.

Most severe toxicity.

Pneumonitis can progress to potentially fatal pulmonary fibrosis.

Most frequently with total dosages >400 units, but can occur with lower dosages.

Risk may be increased with filgrastim or other cytokines.

Dyspnea and fine rales are early manifestations.

Perform chest radiographs every 1–2 weeks and sequential measurement of pulmonary diffusion capacity for carbon monoxide (DLco) monthly during therapy.

Dosage modification or drug discontinuance may be necessary. (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).

Sudden onset of acute chest pain may be first sign of pleuropericarditis.

Dosage modification may be necessary in patients experiencing acute chest pain syndrome suggestive of pleuropericarditis.

Raynaud's phenomenon, possibly due to bleomycin, combination therapy (e.g., vinblastine, cisplatin), underlying cancer or vascular compromise, or combination of factors.

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).

Usually occurs during the second or third week of bleomycin therapy after a cumulative dose of 150–200 units.

Most frequent toxicity, occurring in 50% of patients.

Discontinuance of bleomycin may be necessary.

Renal and Hepatic Toxicity

Begins as deterioration in renal or liver function tests; may occur anytime after bleomycin initiation.

Febrile Reactions

Fever and chills are frequent, mainly with large single doses within a few hours of administration and persisting for 4–12 hours.

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.

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.

Intrapleural Risks

Rarely, pulmonary toxicity.

Local pain.

Hypotension, which may require treatment.

Very rarely, death, but patients were very seriously ill prior to treatment.

Specific Populations

Pregnancy

Category D.

Lactation

Not known whether bleomycin is distributed into milk. Use not recommended.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Greater risk of pulmonary toxicity in patients >70 years of age than in younger patients.

Titrate dosage carefully.

Renal Impairment

Use with extreme caution in patients with clinically important renal impairment.

Common Adverse Effects

With IV administration, fever, chills, vomiting, and anorexia/weight loss (which may persist long after discontinuance of therapy). Mucocutaneous and dermatologic effects are most common and pulmonary toxicity is most serious. (See Major Toxicities under Cautions.)

With intracavitary administration into the pleural space, chest pain and fever.

Interactions for Bleomycin

Specific Drugs

Drug

Interaction

Comments

Antineoplastic agents

Increased risk of bleomycin-induced pulmonary toxicity

Use with caution; pulmonary toxicity possible at lower total bleomycin dosages

Filgrastim and other cytokines

Increased risk of bleomycin-induced pulmonary toxicity

Use with caution; pulmonary toxicity possible at lower total bleomycin dosages

Vitamins (e.g., vitamin C, riboflavin)

Bleomycin shown to be inactivated in vitro by ascorbic acid and riboflavin

Bleomycin Pharmacokinetics

Absorption

Not appreciably absorbed orally; must be administered parenterally for systemic effect.

Following intrapleural administration, systemic absorption is about 45%.

Onset

Improvement in Hodgkin’s disease or testicular cancer usually evident within 2 weeks.

Improvement in squamous cell carcinoma usually evident within 3 weeks.

Distribution

Extent

Distributed mainly into skin, lungs, kidneys, peritoneum, and lymphatics in animals.

Concentrations higher in tumor cells of skin and lungs relative to hematopoietic tissue.

Elimination

Metabolism

Metabolic fate not determined.

Elimination Route

Excreted principally in urine (60–70%) as active drug.

Half-life

Clcr>35 mL/minute: serum or plasma terminal half-life of about 2 hours.

Clcr<35 mL/minute: terminal half-life inversely related to creatinine clearance.

Special Populations

Moderately severe renal impairment (Clcr <35 mL/minute) decreases renal clearance; accumulation may occur with severe renal impairment.

Stability

Storage

Parenteral

Powder for Injection

2–8°C; do not use after the expiration date is reached.

Reconstituted Solutions

Use reconstituted solutions stored at room temperature within 24 hours.

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.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Inactivated by agents containing sulfhydryl groups, hydrogen peroxide, and ascorbic acid.

Forms Schiff base-type adducts with dextrose.

Solution Compatibility

Compatible

Sodium chloride 0.9%

Incompatible

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

Actions

  • Antineoplastic antibiotic; active against gram-positive and gram-negative bacteria and fungi, but its cytotoxicity precludes its use as an anti-infective agent.

  • 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.

    Inhibits incorporation of thymidine into DNA.

  • Exhibits no immunosuppressive activity.

Advice to Patients

  • Advise patients about risk of pulmonary toxicity and to report any changes in pulmonary function (e.g., wheezing) to their clinician.

  • Advise lymphoma patients of risk of severe idiosyncratic reactions (hypotension, mental confusion, fever, chills, wheezing).

  • Advise patients to report any sudden onset of chest pain to their clinician.

  • Advise patients of dermatologic and mucocutaneous effects and that they may not be apparent for several weeks after 100–200 units have been given.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* 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

AHFS DI Essentials™. © Copyright 2022, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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