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Bleomycin: Drug information

Bleomycin: Drug information
(For additional information see "Bleomycin: Patient drug information" and see "Bleomycin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Experienced 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.

Pharmacologic Category
  • Antineoplastic Agent, Antibiotic
Dosing: Adult

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 (Ref). 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.

Gestational trophoblastic neoplasia, high-risk, refractory

Gestational trophoblastic neoplasia, high-risk, refractory (off-label use): BEP regimen: IV: 30 units once weekly, on days 1, 8, and 15 of a 3-week treatment cycle (in combination with etoposide, cisplatin, and WBC growth factor support); continue for at least 2 treatment cycles after a normal hCG level; maximum cumulative bleomycin dose: 270 units (Ref).

Hodgkin lymphoma

Hodgkin lymphoma (off-label dosing):

ABVD regimen: IV: 10 units/m2 on days 1 and 15 of a 28-day treatment cycle (in combination with doxorubicin, vinblastine, and dacarbazine) for 2 to 6 cycles (Ref). The number of cycles required and follow-up treatment may be determined by PET scan after 2 cycles (Ref).

BEACOPP and escalated BEACOPP regimens: IV: 10 units/m2 on day 8 of a 21-day treatment cycle (in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for 4 to 8 cycles; growth factor support is administered with escalated BEACOPP (Ref).

Escalated BEACOPP plus ABVD regimen: IV: 10 units/m2 on day 8 of a 21-day treatment cycle (in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and growth factor support) for 2 cycles, followed by 2 cycles of the ABVD regimen (Ref).

EBVP regimen: IM, IV: 10 units/m2 on day 1 of a 21-day treatment cycle (in combination with epirubicin, vinblastine, and prednisone) for 6 cycles, then followed by radiation therapy (Ref).

Stanford V regimen: IV: 5 units/m2 dosed weekly on weeks 2, 4, 6, 8, 10, and 12 (in combination with mechlorethamine, vinblastine, vincristine, doxorubicin, etoposide, and prednisone) (Ref).

Test dose for lymphoma patients : Note: Test doses may not be predictive of a reaction (Ref) and/or may produce false-negative results.

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.

Malignant pleural effusion

Malignant pleural effusion: Intrapleural: 60 units as a single instillation; mix in 50 to 100 mL of NS.

Ovarian germ cell tumors

Ovarian germ cell tumors (off-label use): BEP regimen: IV: 30 units/dose on days 1, 8, and 15 of a 21-day treatment cycle for 3 cycles (in combination with etoposide and cisplatin) (Ref) or 15 units/m2 day 1 of a 21-day treatment cycle for 4 cycles (in combination with etoposide and cisplatin) (Ref).

Testicular cancer

Testicular cancer (off-label dosing): BEP regimen: IV: 30 units/dose on days 1, 8, and 15 of a 21-day treatment cycle for 3 or 4 cycles (in combination with etoposide and cisplatin) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Altered kidney function:

Manufacturer's labeling (CrCl estimated using the Cockcroft-Gault formula):

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl 40 to 50 mL/minute: Reduce dose to 70% of normal dose.

CrCl 30 to 40 mL/minute: Reduce dose to 60% of normal dose.

CrCl 20 to 30 mL/minute: Reduce dose to 55% of normal dose.

CrCl 10 to 20 mL/minute: Reduce dose to 45% of normal dose.

CrCl 5 to 10 mL/minute: Reduce dose to 40% of normal dose.

The following adjustments have also been recommended:

CrCl-based dosing:

CrCl 46 to 60 mL/minute: Reduce dose to 70% of normal dose (Ref).

CrCl 31 to 45 mL/minute: Reduce dose to 60% of normal dose (Ref).

CrCl <30 mL/minute: Consider use of alternative drug (Ref).

eGFR-based dosing:

eGFR >50 mL/minute/1.73 m2: No dosage adjustment necessary (Ref).

eGFR 10 to 50 mL/minute/1.73 m2: Reduce dose to 75% of normal dose (Ref).

eGFR <10 mL/minute/1.73 m2: Reduce dose to 50% of normal dose (Ref).

Hemodialysis, intermittent (thrice weekly): Consider reducing dose to 50% of normal dose (Ref).

CRRT: Reduce dose to 75% of normal dose (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment for hepatic impairment is not necessary (Ref).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: 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 patients with a BMI ≥30 kg/m2 (Ref).

Dosing: Adjustment for Toxicity: Adult

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 (Ref).

Dosing: Older Adult

Refer to adult dosing. The incidence of pulmonary toxicity is higher in patients >70 years of age.

Dosing: Pediatric

(For additional information see "Bleomycin: Pediatric drug information")

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 (Ref). 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 (Ref); no routine prophylaxis is recommended (Ref).

Test dose for lymphoma patients

Test dose for lymphoma patients: Limited data available: Note: Test doses may not be predictive of a reaction (Ref) 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

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) (Ref)

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 (Ref)

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 (Ref)

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 (Ref)

Malignant germ cell cancer

Malignant germ cell cancer (combination therapy): Limited data available: PEB regimen (Ref):

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.

Adult:

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: Kidney Impairment: Pediatric

There are no pediatric specific recommendations; based on experience in adult patients, dosing adjustment suggested.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, adjustment for hepatic impairment is not necessary (Ref).

Adverse Reactions

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.

>10%:

Cardiovascular: Phlebitis

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

Contraindications

Hypersensitivity or idiosyncratic reaction to bleomycin or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: May cause hepatic toxicity.

• Idiosyncratic reaction: 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: 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 bleomycin 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.

Disease-related concerns:

• 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.

Special populations:

• 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).

Other warnings/precautions:

• 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.

Dosage Forms Considerations

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 (1,000 international units = 1 USP unit).

Dosage Forms: US

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)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (reconstituted) (Bleomycin Sulfate Injection)

15 unit (per each): $36.82 - $68.64

30 unit (per each): $80.03 - $127.32

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Generic: 15 units (1 ea)

Administration: Adult

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.

Administration: Pediatric

IM, SubQ: Administer at a concentration of 3 to 15 units/mL; may cause pain at injection site

IV: Administer IV slowly over at least 10 minutes; may be further diluted for administration by continuous IV infusion; slower administration may produce less severe pulmonary toxicity

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Head and neck cancers: Treatment of squamous cell carcinoma 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.

Use: Off-Label: Adult

Germ cell tumors, malignant; Gestational trophoblastic neoplasia, high-risk, refractory

Medication Safety Issues
Sound-alike/look-alike issues:

Bleomycin may be confused with Cleocin, clindamycin.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

International issues:

Some products available internationally may have vial strength and dosing expressed as international units or milligrams (instead of units or USP units). Refer to prescribing information for specific strength and dosing information.

Other safety concerns:

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 (1,000 international units = 1 USP unit).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Brentuximab Vedotin: May enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Risk X: Avoid combination

Gemcitabine: May enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Risk C: 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. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Oxygen: May enhance the adverse/toxic effect of Bleomycin. Specifically, bleomycin pulmonary toxicity may be enhanced. Management: Attempt to keep oxygen at a concentration equal to that of room air (eg, 25%), during surgery and the post-operative period for patients receiving bleomycin. Monitor patients carefully for pulmonary toxicity, especially those receiving fluid replacement. Risk D: 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. Risk D: Consider therapy modification

Phenytoin: Bleomycin may decrease the serum concentration of Phenytoin. Risk C: Monitor therapy

Reproductive Considerations

According to the manufacturer, patients who could become pregnant should avoid becoming pregnant during bleomycin treatment.

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 (ESMO [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 (ESMO [Peccatori 2013]; Follows 2014).

Breastfeeding Considerations

It is not known if bleomycin is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.

Monitoring Parameters

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.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: IM, SubQ, and intrapleural administration: 100%, 70%, and 45%, respectively, of IV serum concentrations

Distribution: Vd: IV: 17.5 L/m2

Protein binding: 1%

Metabolism: Enzymatic inactivation by bleomycin hydrolase, a cytosolic cysteine proteinase enzyme; bleomycin hydrolase is widely distributed in normal tissues (except for the skin and lungs)

Half-life elimination: Terminal: IV: 2 hours

Time to peak, serum: IM, SubQ, Intrapleural: 30 to 60 minutes

Excretion: Urine (~65% [IV], 40% [Intrapleural])

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: The half-life increases exponentially as CrCl decreases.

Pediatric: Children younger than 3 years of age have a higher total body clearance than adults.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Bileco | Bleocris | Bleomicina asofarma | Bleomicina dosa | Blocamicina;
  • (AT) Austria: Bleomycin;
  • (AU) Australia: Blenamax | Blenoxane | Bleo | Bleomycin cipla | Bleomycin sulphate;
  • (BE) Belgium: Bleomin | Bleomycine | Bleomycine accord;
  • (BG) Bulgaria: Bleocin | Bleomycin | Bleomycin medac | Bleomycine Teva;
  • (BR) Brazil: Blenoxane | Bonar | Cinaleo | Tecnomicina | Tevableo;
  • (CH) Switzerland: Bleomycin Teva;
  • (CL) Chile: Blexit;
  • (CN) China: Bleocin | Bleomycin;
  • (CO) Colombia: Blenamax | Bleolem | Bleomicina | Bleoseven 15 | Blexicip | Blomindex | Oncobleocin;
  • (CZ) Czech Republic: Bleomedac | Bleomycin Teva;
  • (DE) Germany: Bleo cell | Bleomedac | Bleomicina | Bleomycin | Bleomycin Teva | Bleomycinum;
  • (DO) Dominican Republic: Bleocip;
  • (EC) Ecuador: Bleocris | Bleomicina | Oncobleocin;
  • (EE) Estonia: Bleo cell | Bleocel | Bleolem | Bleomycin medac;
  • (EG) Egypt: Bleocin;
  • (ES) Spain: Bleomicina | Bleomicina accord;
  • (ET) Ethiopia: Bleocin | Bleomycin;
  • (FI) Finland: Bleomycin;
  • (FR) France: Bleomycine Bellon | Bleomycine Teva;
  • (GB) United Kingdom: Bleo kyowa | Bleomycin;
  • (GR) Greece: Bleocin;
  • (HK) Hong Kong: Bleocin;
  • (HR) Croatia: Bleocin S;
  • (HU) Hungary: Bleo cell | Bleomycin-teva;
  • (ID) Indonesia: Bleocin;
  • (IN) India: Bleocel | Bleochem | Bleocip | Bleomycin sulphate | Bleonco | Bleotex | Lyoble | Tumocin;
  • (IT) Italy: Bleomicina | Bleomicina crinos | Bleomicina Teva | Bleoprim;
  • (JP) Japan: Bleo;
  • (KE) Kenya: Bleochem | Bleocip;
  • (KR) Korea, Republic of: Bleocin | Bloicin s | Union bleomycin sulfate;
  • (LB) Lebanon: Lyoble;
  • (LT) Lithuania: Bleocin | Bleolem | Bleomycetin | Bleomycin medac | Bleomycin Mylan | Bleomycin Teva;
  • (LU) Luxembourg: Bleomycine;
  • (LV) Latvia: Bleomycetin | Bleomycin | Bleomycin medac | Bleomycin Teva;
  • (MA) Morocco: Bleomycine | Blucin;
  • (MX) Mexico: Bleolem | Bleomax | Bleomicina | Blomindex;
  • (MY) Malaysia: Blenamax;
  • (NL) Netherlands: Bleomedac | Bleomycine;
  • (NO) Norway: Bleomicina | Bleomycin;
  • (PE) Peru: Bileco | Bleocin;
  • (PH) Philippines: Bemocin | Tumocin;
  • (PK) Pakistan: Bleocin | Bleomycin | Bleotex;
  • (PL) Poland: Blemisin | Bleocel | Bleocin | Bleomedac | Bleomycin | Bleomycin Hexal | Bleomycin Teva;
  • (PR) Puerto Rico: Blenoxane | Bleo | Bleomycin;
  • (PT) Portugal: Bleocin | Bleomedac | Bleomicina ApS | Bleomicina Teva;
  • (PY) Paraguay: Bleocris | Bleomicina fapasa;
  • (RO) Romania: Bleocin | Bleomicina accord | Bleomycin medac;
  • (RU) Russian Federation: Blenamax | Bleocin | Bleomycetin | Bleomycetin hydrochloride | Bleomycin ronc | Maltin | Vero bleomycin;
  • (SA) Saudi Arabia: Bemocin;
  • (SE) Sweden: Bleomycin baxter;
  • (SI) Slovenia: Blenamax | Bleomycin sulphate | Bleomycinum;
  • (SK) Slovakia: Bleocin | Bleomedac;
  • (TH) Thailand: Blenamax | Bleochem | Bleocin | Bleolem;
  • (TN) Tunisia: Bleomycine;
  • (TR) Turkey: Blemisin | Bleolem;
  • (TW) Taiwan: Bleocin | Bleomycin;
  • (UA) Ukraine: Bleocin | Bleocin c | Bleolem | Bleomycin | Lyoble 15;
  • (UG) Uganda: Bleosol;
  • (UY) Uruguay: Bileco | Bleocina | Bleocris | Bleomicina;
  • (ZA) South Africa: Blenamax | Blenoxane | Bleocel | Bleolem;
  • (ZM) Zambia: Bleocip | Bleomycin;
  • (ZW) Zimbabwe: Bemocin | Bleocip | Blesol
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007:97.
  3. Azambuja E, Fleck JF, Batista RG, et al. Bleomycin Lung Toxicity: Who are the Patients With Increased Risk? Pulm Pharmacol Ther. 2005;18(5):363-366. [PubMed 15939315]
  4. Blenoxane (bleomycin) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; April 2010.
  5. Bleomycin [prescribing information]. Lake Forest, IL: Hospira; May 2017.
  6. Bleomycin [product monograph]. Richmond Hill, ON: Fresenius Kabi Canada Ltd; February 2016.
  7. Bonadonna G, Bonfante V, Viviani S, Di Russo A, Villani F, Valagussa P. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004;22(14):2835-2841. doi:10.1200/JCO.2004.12.170 [PubMed 15199092]
  8. Borchmann P, Plütschow A, Kobe C, et al. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(2):223-234. doi:10.1016/S1470-2045(20)30601-X [PubMed 33539742]
  9. Carver JR, Shapiro CL, Ng A, et al. American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects. J Clin Oncol. 2007;25(25):3991-4008. [PubMed 17577017]
  10. Culine S, Kramar A, Théodore C, et al. Randomized Trial Comparing Bleomycin/Etoposide/Cisplatin With Alternating Cisplatin/Cyclophosphamide/Doxorubicin and Vinblastine/Bleomycin Regimens of Chemotherapy for Patients With Intermediate- and Poor-Risk Metastatic Nonseminomatous Germ Cell Tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol. 2008;26(3):421-427. [PubMed 18202419]
  11. Cushing B, Giller R, Cullen JW, et al. Randomized Comparison of Combination Chemotherapy With Etoposide, Bleomycin, and Either High-Dose or Standard-Dose Cisplatin in Children and Adolescents With High-Risk Malignant Germ Cell Tumors: A Pediatric Intergroup Study -- Pediatric Oncology Group 9049 and Children's Cancer Group 8882. J Clin Oncol. 2004;22(13):2691-2700. [PubMed 15226336]
  12. Dann EJ, Bar-Shalom R, Tamir A, et al. Risk-Adapted BEACOPP Regimen Can Reduce the Cumulative Dose of Chemotherapy for Standard and High-Risk Hodgkin Lymphoma With No Impairment of Outcome. Blood. 2007;109(3):905-909. [PubMed 17018856]
  13. Dharmarajan KV, Friedman DL, Schwartz CL, et al. Patterns of relapse from a phase 3 study of response-based therapy for intermediate-risk Hodgkin lymphoma (AHOD0031): a report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys. 2015;92(1):60-66. [PubMed 25542311]
  14. de Wit R, Skoneczna I, Daugaard G, et al. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983. J Clin Oncol. 2012;30(8):792-799. [PubMed 22271474]
  15. Diehl V, Franklin J, Pfreundschuh M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared With COPP-ABVD for Advanced Hodgkin's Disease. N Engl J Med. 2003;348(24):2386-2395. [PubMed 12802024]
  16. Dupuis LL, Boodhan S, Holdsworth M, et al. Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patient. Pediatr Blood Cancer. 2013;60(7):1073-1082. [PubMed 23512831]
  17. Dupuis LL, Boodhan S, Sung L, et al; Pediatric Oncology Group of Ontario. Guideline for the classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2011;57(2):191-198. [PubMed 21465637]
  18. Eiriksson L, Dean E, Sebastianelli A, et al. Guideline no. 408: management of gestational trophoblastic diseases. J Obstet Gynaecol Can. 2021;43(1):91-105.e1. doi:10.1016/j.jogc.2020.03.001 [PubMed 33384141]
  19. Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009;27(27):4548-4554. doi:10.1200/JCO.2008.19.8820 [PubMed 19704068]
  20. Engert A, Franklin J, Eich HT, et al. Two Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Plus Extended-Field Radiotherapy is Superior to Radiotherapy Alone in Early Favorable Hodgkin's Lymphoma: Final Results of the GHSG HD7 Trial. J Clin Oncol. 2007;25(23):3495-3502. [PubMed 17606976]
  21. Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010;363(7):640-652. doi:10.1056/NEJMoa1000067 [PubMed 20818855]
  22. Floyd JD, Nguyen DT, Lobins RL, et al. Cardiotoxicity of Cancer Therapy. J Clin Oncol. 2005;23(30):7685-7696. [PubMed 16234530]
  23. Follows GA, Ardeshna KM, Barrington SF, et al. Guidelines for the first line management of classical Hodgkin lymphoma. Br J Haematol. 2014;166(1):34-49. [PubMed 24712411]
  24. Friedman DL, Chen L, Wolden S, et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014;32(32):3651-3658. [PubMed 25311218]
  25. Gordon LI, Hong F, Fisher RI, et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013;31(6):684-691. [PubMed 23182987]
  26. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
  27. Horning SJ, Williams J, Bartlett NL, et al. Assessment of the Stanford V Regimen and Consolidative Radiotherapy for Bulky and Advanced Hodgkin's Disease: Eastern Cooperative Oncology Group Pilot Study E1492. J Clin Oncol. 2000;18(5):972-980. [PubMed 10694546]
  28. Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA. Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol. 2002;20(3):630-637. [PubMed 11821442]
  29. Hoskin PJ, Lowry L, Horwich A, et al. Randomized Comparison of the Stanford V Regimen and ABVD in the Treatment of Advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol. 2009;27(32):5390-5396. [PubMed 19738111]
  30. Huang TT, Hudson MM, Stokes DC, et al. Pulmonary Outcomes in Survivors of Childhood Cancer: A Systematic Review. Chest. 2011;140(4):881-901. [PubMed 21415131]
  31. Hutchinson RJ, Fryer CJ, Davis PC, et al. MOPP or Radiation in Addition to ABVD in the Treatment of Pathologically Staged Advanced Hodgkin's Disease in Children: Results of the Children's Cancer Group Phase III Trial. J Clin Oncol. 1998;16(3):897-906. [PubMed 9508171]
  32. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  33. Ibrahimi OA, Anderson RR. Images in Clinical Medicine. Bleomycin-Induced Flagellate Hyperpigmentation. N Engl J Med. 2010;363(24):e36. [PubMed 21142531]
  34. Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016;374(25):2419-2429. [PubMed 27332902]
  35. Johnson PW, Radford JA, Cullen MH, et al. Comparison of ABVD and Alternating or Hybrid Multidrug Regimens for the Treatment of Advanced Hodgkin's Lymphoma: Results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005;23(36):9208-9218. [PubMed 16314615]
  36. Kelly KM, Hutchinson RJ, Sposto R, et al; Children's Oncology Group. Feasibility of upfront dose-intensive chemotherapy in children with advanced-stage Hodgkin's lymphoma: preliminary results from the Children's Cancer Group Study CCG-59704. Ann Oncol. 2002;13(suppl 1):107-111. doi:10.1093/annonc/13.s1.107 [PubMed 12078889]
  37. Kelly KM, Sposto R, Hutchinson R, et al. BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group. Blood. 2011;117(9):2596-2603. [PubMed 21079154]
  38. King PD, Perry MC. Hepatotoxicity of Chemotherapy. Oncologist. 2001;6(2):162-176. [PubMed 11306728]
  39. Kintzel PE, Dorr RT. Anticancer Drug Renal Toxicity and Elimination: Dosing Guidelines for Altered Renal Function. Cancer Treat Rev. 1995;21(1):33-64. [PubMed 7859226]
  40. Krens SD, Lassche G, Jansman FGA, et al. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol. 2019;20(4):e200-e207. doi:10.1016/S1470-2045(19)30145-7 [PubMed 30942181]
  41. Kung FH, Schwartz CL, Ferree CR, et al. POG 8625: A Randomized Trial Comparing Chemotherapy With Chemoradiotherapy for Children and Adolescents With Stages I, IIA, IIIA1 Hodgkin Disease: A Report From the Children's Oncology Group. J Pediatr Hematol Oncol. 2006;28(6):362-368. [PubMed 16794504]
  42. Lam MS. The Need for Routine Bleomycin Test Dosing in the 21st Century. Ann Pharmacother. 2005;39(11):1897-1902. [PubMed 16219896]
  43. Lauritsen J, Kier MG, Bandak M, et al. Pulmonary function in patients with germ cell cancer treated with bleomycin, etoposide, and cisplatin. J Clin Oncol. 2016;34(13):1492-1499. [PubMed 26903578]
  44. Lurain JR, Nejad B. Secondary chemotherapy for high-risk gestational trophoblastic neoplasia. Gynecol Oncol. 2005;97(2):618-623. doi: 10.1016/j.ygyno.2005.02.004 [PubMed 15863169]
  45. Lurain JR, Schink JC. Importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia. J Reprod Med. 2012;57(5-6):219-224. [PubMed 22696816]
  46. Lurain JR, Singh DK, Schink JC. Management of metastatic high-risk gestational trophoblastic neoplasia: FIGO stages II-IV: risk factor score > or = 7. J Reprod Med. 2010;55(5-6):199-207. [PubMed 20626175]
  47. Morgan C, Tillett T, Braybrooke J, et al. Management of Uncommon Chemotherapy-Induced Emergencies. Lancet Oncol. 2011;12(8):806-814. [PubMed 21276754]
  48. Nichols CR, Catalano PJ, Crawford ED, et al. Randomized Comparison of Cisplatin and Etoposide and Either Bleomycin or Ifosfamide in Treatment of Advanced Disseminated Germ Cell Tumors: An Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998;16(4):1287-1293. [PubMed 9552027]
  49. O'Sullivan JM, Huddart RA, Norman AR, Nicholls J, Dearnaley DP, Horwich A. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Ann Oncol. 2003;14(1):91-96. doi:10.1093/annonc/mdg020 [PubMed 12488299]
  50. Peccatori FA, Azim HA Jr, Orecchia R, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl 6):vi160-170. [PubMed 23813932]
  51. Perry MC. Chemotherapeutic agents: bleomycin. The Chemotherapy Source Book. 5th ed. Philadelphia, PA: 2012.
  52. Saxman SB, Finch D, Gonin R, et al. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience. J Clin Oncol. 1998;16(2):702-706. doi:10.1200/JCO.1998.16.2.702 [PubMed 9469360]
  53. Schwartz CL, Constine LS, Villaluna D, et al. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009;114(10):2051-2059. [PubMed 19584400]
  54. Sleijfer S. Bleomycin-Induced Pneumonitis. Chest. 2001;120(2):617-624. [PubMed 11502668]
  55. Stefanou A, MacCallum P, and Siderov J. Errors due to bleomycin nomenclature. BMJ. 2001;322(7299):548.
  56. Straus DJ, Portlock CS, Qin J, et al. Results of a Prospective Randomized Clinical Trial of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) Followed by Radiation Therapy (RT) Versus ABVD Alone for stages I, II, and IIIA Nonbulky Hodgkin Disease. Blood. 2004;104(12):3483-3489. [PubMed 15315964]
  57. Thomas J, Fermé C, Noordijk EM, et al. Comparison of 36 Gy, 20 Gy, or no radiation therapy after 6 cycles of EBVP chemotherapy and complete remission in early-stage Hodgkin lymphoma without risk factors: results of the EORT-GELA H9-F Intergroup randomized trial. Int J Radiat Oncol Biol Phys. 2018;100(5):1133-1145. doi:10.1016/j.ijrobp.2017.10.015 [PubMed 29229324]
  58. Tobias JS, Monson K, Gupta N, et al. Chemoradiotherapy for Locally Advanced Head and Neck Cancer: 10-year Follow-Up of the UK Head and Neck (UKHAN1) Trial. Lancet Oncol. 2010;11(1):66-74. [PubMed 19875337]
  59. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed October 5, 2016.
  60. von Tresckow B, Plütschow A, Fuchs M, et al. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012;30(9):907-913. doi:10.1200/JCO.2011.38.5807 [PubMed 22271480]
  61. Wiernik PH, Hong F, Glick JH, et al. Radiation Therapy Compared With Chemotherapy for Consolidation of Chemotherapy-Induced Remission of Advanced Hodgkin Lymphoma: A Study by the Eastern Co-Operative Oncology Group (E1476) With >20 Years Follow-Up. Leuk Lymphoma. 2009;50(10):1632-1641. [PubMed 19863338]
  62. Williams S, Blessing JA, Liao SY, et al. Adjuvant Therapy of Ovarian Germ Cell Tumors With Cisplatin, Etoposide, and Bleomycin: A Trial of the Gynecologic Oncology Group. J Clin Oncol. 1994;12(4):701-706. [PubMed 7512129]
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