Medically reviewed by Drugs.com. Last updated on Jul 31, 2020.
(blee oh MYE sin)
- Bleomycin Sulfate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection [preservative free]:
Generic: 15 units (1 ea); 30 units (1 ea)
- Antineoplastic Agent, Antibiotic
Bleomycin inhibits synthesis of DNA; binds to DNA leading to single- and double-strand breaks; also inhibits (to a lesser degree) RNA and protein synthesis
IM, SubQ, and intrapleural administration: 100%, 70%, and 45%, respectively, of IV serum concentrations
Vd: IV: 17.5 L/m2
Enzymatic inactivation by bleomycin hydrolase, a cytosolic cysteine proteinase enzyme; bleomycin hydrolase is widely distributed in normal tissues (except for the skin and lungs)
Urine (~65% [IV], 40% [Intrapleural])
Time to Peak
Serum: IM, SubQ, Intrapleural: 30 to 60 minutes
Terminal: IV: 2 hours
Special Populations: Renal Function Impairment
The half-life increases exponentially as CrCl decreases.
Special Populations: Children
Children younger than 3 years of age have a higher total body clearance than adults.
Use: Labeled Indications
Head and neck cancers: Treatment of squamous cell carcinomas of the head and neck
Hodgkin lymphoma: Treatment of Hodgkin lymphoma
Malignant pleural effusion: Sclerosing agent for malignant pleural effusion
Testicular cancer: Treatment of testicular cancer
Off Label Uses
Germ cell tumors, malignant
Data from a limited number of patients studied suggest that bleomycin (in combination with cisplatin and etoposide) may be beneficial for the treatment of ovarian germ cell tumors when used after tumor removal and thorough surgical staging [Williams 1994]. Data from a clinical trial in children and adolescents with high-risk malignant germ cell tumors suggest that bleomycin (in combination with cisplatin and etoposide) may be beneficial for the treatment of advanced testicular or ovarian germ cell tumors [Cushing 2004]. Additional data may be necessary to further define the role of bleomycin in this condition.
Hypersensitivity to bleomycin or any component of the formulation
Note: The risk for pulmonary toxicity increases with age >70 years and cumulative lifetime dose of >400 units. International considerations: Dosages below expressed as USP units; 1 USP unit = 1 mg (by potency) = 1,000 international units (Stefanou 2001). During shortages within the US, temporary importation of international products may be allowed by the FDA. The imported bleomycin vial and product labeling may express strength and dosing as international units instead of USP units.
Hodgkin lymphoma (off-label dosing): IV:
ABVD regimen: 10 units/m2 days 1 and 15 of a 28-day treatment cycle (in combination with doxorubicin, vinblastine, and dacarbazine) (Straus 2004)
BEACOPP regimen: 10 units/m2 day 8 of a 21-day treatment cycle (in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) (Dann 2007, Diehl 2003)
Stanford V regimen: 5 units/m2/dose in weeks 2, 4, 6, 8, 10 and 12 (in combination with mechlorethamine, vinblastine, vincristine, doxorubicin, etoposide, and prednisone) (Horning 2002; Horning 2000)
Test dose for lymphoma patients: IM, IV, SubQ: Due to the possibility of an anaphylactoid reaction, the manufacturer recommends administering bleomycin 2 units or less before the first 2 doses; if no acute reaction occurs, then the regular dosage schedule may be followed. Monitor carefully, particularly following the first 2 doses. Note: Test doses may not be predictive of a reaction (Lam 2005) and/or may produce false-negative results.
Testicular cancer (off-label dosing): IV: BEP regimen: 30 units/dose days 1, 8, and 15 of a 21-day treatment cycle for 4 cycles (in combination with etoposide and cisplatin) (Culine 2008; Nichols 1998)
Malignant pleural effusion: Intrapleural: 60 units as a single instillation; mix in 50 to 100 mL of NS
Ovarian germ cell cancer (off-label use): BEP regimen: IV: 30 units/dose days 1, 8, and 15 of a 21-day treatment cycle for 3 cycles (in combination with etoposide and cisplatin) (Williams 1994) or 15 units/m2 day 1 of a 21-day treatment cycle for 4 cycles (in combination with etoposide and cisplatin) (Cushing 2004)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Refer to adult dosing. The incidence of pulmonary toxicity is higher in patients >70 years of age.
Note: The risk for pulmonary toxicity increases with cumulative lifetime dose >400 USP units. International considerations: Dosages below are expressed as USP units; 1 USP unit = 1 mg (by potency) = 1,000 international units (Stefanou 2001). During shortages within the US, temporary importation of international products may be allowed by the FDA. The imported bleomycin vial and product labeling may express strength and dosing as international units instead of USP units. Refer to individual protocols for specific dosage and interval information. All doses of bleomycin are associated with a minimal emetic potential (Dupuis 2011); no routine prophylaxis is recommended (Dupuis 2013).
Test dose for lymphoma patients: Limited data available: Note: Test doses may not be predictive of a reaction (Lam 2005) and/or may produce false-negative results; some protocols no longer require; refer to institution/protocol specific guidelines. Children and Adolescents: IM, IV, SubQ: Because of the possibility of an anaphylactoid reaction, the manufacturer recommends administering 1 to 2 units of bleomycin before the first 1 to 2 doses; monitor vital signs every 15 minutes; wait a minimum of 1 hour before administering remainder of dose; if no acute reaction occurs, then the regular dosage schedule may be followed
Hodgkin lymphoma (combination regimen): Limited data available:
ABVE-PC (intermediate-risk or high-risk Hodgkin lymphoma): Children and Adolescents: IV or SubQ: 5 units/m2 on day 1 and 10 units/m2 on day 8 of a 21-day cycle for 2 to 4 cycles (in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide) (Dharmarajan 2015; Friedman 2014; Schwartz 2009)
ABVD (high-risk Hodgkin lymphoma): Children and Adolescents: IV: 10 units/m2 on days 1 and 15 of a 28-day treatment cycle for 2 to 6 cycles in combination with doxorubicin, vinblastine, dacarbazine (Hutchinson 1998)
BEACOPP (high-risk Hodgkin lymphoma): Children and Adolescents: IV: 10 units/m2 on day 7 of a 21-day treatment cycle for 2 to 4 cycles in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (Kelly 2002)
Stanford V (high-risk Hodgkin lymphoma): Adolescent ≥16 years: IV: 5 units/m2/dose in weeks 2, 4, 6, 8, 10, and 12 of a 12-week treatment cycle for 1 cycle in combination with mechlorethamine, vinblastine, vincristine, doxorubicin, etoposide, and prednisone (Gordon 2013; Horning 2000; Horning 2002)
Malignant germ cell cancer (combination therapy): Limited data available: PEB regimen (Cushing 2004):
Infants: IV: 0.5 mg/kg on day 1 of a 21-day treatment cycle for 4 cycles in combination with cisplatin and etoposide
Children and Adolescents: IV: 15 units/m2 on day 1 of a 21-day treatment cycle for 4 cycles in combination with cisplatin and etoposide
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available.
Pulmonary changes: Discontinue until determined not to be drug-related.
Pulmonary diffusion capacity for carbon monoxide (DLCO) <30% to 35% of baseline in adults: Discontinue treatment.
Dosing: Adjustment for Toxicity
Pulmonary toxicity: Discontinue until determined not to be drug-related.
Pulmonary diffusion capacity for carbon monoxide (DLCO) <30% to 35% of baseline: Discontinue treatment.
Pulmonary diffusing capacity for carbon monoxide corrected for hemoglobin content [DLCOc] decrease of more than 25% during therapy (compared with baseline): Consider discontinuing bleomycin to avoid further pulmonary toxicity (Lauritsen 2016).
ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Fixed doses (dosing which is independent of body weight or BSA), are used in some protocols (eg, testicular cancer); due to toxicity concerns, the same fixed dose should also be considered for obese patients (Griggs 2012).
Note: During shortages within the US, temporary importation of international products may be allowed by the FDA. Refer to specific product labeling for reconstitution and preparation information.
For IV use, reconstitute 15-unit vial with 5 mL with NS and the 30-unit vial with 10 mL NS; for IM or SubQ use, reconstitute 15-unit vial with 1 to 5 mL of SWFI, BWFI, or NS and the 30-unit vial with 2 to 10 mL of SWFI, BWFI, or NS. For intrapleural use, mix in 50 to 100 mL of NS.
IV: IV doses should be administered slowly over 10 minutes (according to the manufacturer's labeling).
IM or SubQ: May cause pain at injection site
Intrapleural: 60 units in 50 to 100 mL NS; use of topical anesthetics or opioid analgesia is usually not necessary
Monitor for hypersensitivity, particularly following the first 2 doses in patients with lymphoma.
Store intact vials at 2°C to 8°C (36°F to 46°F). Stable for 24 hours in NS at room temperature.
Brentuximab Vedotin: May enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Avoid combination
Gemcitabine: May enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Monitor therapy
Granulocyte Colony-Stimulating Factors: May enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of bleomycin. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification
Phenytoin: Bleomycin may decrease the serum concentration of Phenytoin. Monitor therapy
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined. The pathogenesis of respiratory adverse effects is not certain, but may be due to damage of pulmonary, vascular, or connective tissue. Response to steroid therapy is variable and somewhat controversial.
Central nervous system: Tumor pain
Dermatologic: Hyperpigmentation (50%), atrophic striae (≤50%), erythema (≤50%), exfoliation of the skin (≤50%; particularly on the palmar and plantar surfaces of the hands and feet), hyperkeratosis (≤50%), localized vesiculation (≤50%), skin rash (≤50%), skin sclerosis (≤50%), alopecia (may be dose-related and reversible with discontinuation), nailbed changes (may be dose-related and reversible with discontinuation)
Endocrine & metabolic: Weight loss
Gastrointestinal: Stomatitis (≤30%), mucositis (≤30%), anorexia
Miscellaneous: Febrile reaction (25% to 50%; acute)
1% to 10%:
Dermatologic: Onycholysis, pruritus, thickening of skin
Hypersensitivity: Anaphylactoid reaction (including chills, confusion, fever, hypotension, wheezing; onset may be immediate or delayed for several hours; includes idiosyncratic reaction in 1% of lymphoma patients)
Neuromuscular & skeletal: Scleroderma (diffuse)
Respiratory: Tachypnea (≤5% to 10%), rales (≤5% to 10%), interstitial pneumonitis (acute or chronic: ≤5% to 10%), pulmonary fibrosis (≤5% to 10%), hypoxia (1%)
<1%, postmarketing, and/or case reports: Angioedema, bone marrow depression (rare), cerebrovascular accident, cerebral arteritis, chest pain, coronary artery disease, hepatotoxicity, hyperpigmentation (flagellate), ischemic heart disease, malaise, myocardial infarction, nausea, nephrotoxicity, pericarditis, Raynaud’s phenomenon, scleroderma (scleroderma-like skin changes), Stevens-Johnson syndrome, thrombotic thrombocytopenic purpura, toxic epidermal necrolysis, vomiting
ALERT: U.S. Boxed WarningExperienced physician:
It is recommended that bleomycin be administered under the supervision of a qualified physician 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 toxicity:
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.Idiosyncratic reaction:
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.
Concerns related to adverse effects:
• Hepatotoxicity: May cause hepatic toxicity.
• Idiosyncratic reaction: [US Boxed Warning]: A severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing (similar to anaphylaxis) has been reported in 1% of lymphoma patients treated with bleomycin. Since these reactions usually occur after the first or second dose, careful monitoring is essential after these doses.
• Pulmonary toxicity: [US Boxed Warning]: Occurrence of pulmonary fibrosis (commonly presenting as pneumonitis; occasionally progressing to pulmonary fibrosis) is the most severe toxicity. Risk is higher in elderly patients or patients receiving >400 units total lifetime dose; other possible risk factors include smoking and patients with prior radiation therapy or receiving concurrent oxygen (especially high inspired oxygen doses). A review of patients receiving bleomycin for the treatment of germ cell tumors suggests risk for pulmonary toxicity is increased in patients >40 years of age, with glomerular filtration rate <80 mL/minute, advanced disease, and cumulative doses >300 units (O’Sullivan 2003). Pulmonary toxicity may include bronchiolitis obliterans and organizing pneumonia (BOOP), eosinophilic hypersensitivity, and interstitial pneumonitis, progressing to pulmonary fibrosis (Sleijfer 2001); pulmonary toxicity may be due to a lack of the enzyme which inactivates bleomycin (bleomycin hydrolase) in the lungs (Morgan 2011; Sleijfer 2001), If pulmonary changes occur, withhold treatment and investigate if drug-related. In a study of patients with testicular cancer receiving bleomycin as part of the BEP regimen, pulmonary function testing (including forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], and diffusing capacity of the lungs for carbon monoxide [DLCO]) was performed prior to treatment, before each chemotherapy cycle, and then repeated at 1 year, 3 years, and 5 years during follow up; if the carbon monoxide diffusing capacity corrected for hemoglobin content [DLCOc] decreased more than 25% during therapy (compared with baseline), bleomycin was discontinued to avoid further pulmonary toxicity (Lauritsen 2016).
• Renal toxicity: May cause renal toxicity.
• Hodgkin lymphoma: Positron emission tomography/computed tomography (PET/CT) may have a role in determining early response to therapy in patients with Hodgkin lymphoma; a negative interim PET/CT result after 2 cycles may indicate that bleomycin can be safely omitted from the ABVD treatment regimen (Johnson 2016). Longer follow-up is necessary to determine the effect of bleomycin omission on long-term morbidity and mortality in these patients.
• Renal impairment: Use with caution in patients with renal impairment (CrCl <50 mL/minute), may require dose adjustment.
• Pediatric: In children, a younger age at treatment, cumulative dose ≥400 units/m2 (combined with chest irradiation), and renal impairment are associated with a higher incidence of pulmonary toxicity (Huang, 2011).
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• International issues: Some products available internationally may have vial strength and dosing expressed as international units or milligrams (instead of units or USP units). During shortages within the US, temporary importation of international products may be allowed by the FDA. The imported bleomycin vial and product labeling may express strength and dosing as international units instead of USP units. One USP unit of bleomycin = 1 mg (by potency) = 1,000 international units (Stefanou 2001). Refer to prescribing information for specific dosing information.
• O2 during surgery: Use caution when administering O2 during surgery to patients who have received bleomycin; the risk of bleomycin-related pulmonary toxicity is increased.
Pulmonary function tests, including total lung volume, forced vital capacity, diffusion capacity for carbon monoxide; vital capacity, total lung capacity and pulmonary capillary blood volume may be better indicators of changes induced by bleomycin (Sleifjer 2001); forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], and diffusing capacity of the lungs for carbon monoxide [DLCO]) were performed prior to treatment, before each chemotherapy cycle, and then repeated at 1 year, 3 years, and 5 years during follow up for testicular cancer patients receiving bleomycin (Lauritsen 2016); chest x-ray, renal function, liver function; monitor for signs/symptoms of hypersensitivity; temperature initially; check body weight at regular intervals.
According to the manufacturer, women of childbearing potential should avoid becoming pregnant during bleomycin treatment.
Pregnancy Risk Factor D Pregnancy Considerations
Adverse effects were observed in animal reproduction studies. The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (Peccatori 2013). When multiagent therapy is needed to treat Hodgkin lymphoma during pregnancy, bleomycin (as a component of the ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine] regimen) may be used, starting with the second trimester (Follows 2014; Peccatori 2013).
What is this drug used for?
• It is used to treat cancer.
• It is used to stop fluid buildup in the lung cavity.
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Change in skin or nails
• Skin discoloration
• Mouth sore
• Weight loss
• Lack of appetite
• Hair loss
• Loss of strength and energy
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• Severe dizziness
• Passing out
• Chest pain
• Persistent cough
• Severe mouth irritation
• Severe skin irritation
• Severe application site irritation
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
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