Bleomycin is a chemotherapeutic drug that inhibits the synthesis of DNA by binding to it and inducing breaks in it.

It is used to treat the following conditions:

• Squamous cell carcinomas of the head and neck region

• Treatment of Hodgkin Lymphoma

• Sclerosing agent for malignant pleural effusion

• Testicular cancer

• As off-label use in the treatment of malignant germ cell tumors.

Bleomycin Dose in Adults

Note: 1 USP unit = 1 mg = 1,000 international units.

Off-label dosing in the treatment of Hodgkin lymphoma:

• ABVD regimen:
  • 10 units/m²/day intravenous on days 1 and 15 of a 28-day treatment cycle in combination with doxorubicin, vinblastine, and dacarbazine
• BEACOPP regimen:
  • 10 units/m²/day intravenous on day 8 of a 21-day treatment cycle in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
• Stanford V regimen:
  • 5 units/m²/dose intravenous in weeks 2, 4, 6, 8, 10 and 12 in combination with mechlorethamine, vinblastine, vincristine, doxorubicin, etoposide, and prednisone.
• Test dose for lymphoma patients:
  • A test dose of 2 units or less may be administered as an intravenous, intramuscular, or subcutaneous injection prior to the first dose because of the possibility of an anaphylactoid reaction.
  • The regular dosage schedule may be followed if no reaction is noted.
  • The patient should be monitored for following the first two doses as the test dose may be falsely reassuring.

Off label dosing in the treatment of Testicular cancer:

• BEP regimen:
  • 30 units/dose intravenous on days 1, 8, and 15 of a 21-day treatment cycle for 4 cycles in combination with etoposide and cisplatin.

As a sclerosing agent in the treatment of Malignant pleural effusion:

• 60 units of bleomycin in 50 - 100 ml of 0.9% saline administered as a single dose administered intrapleural.

Off label use in the treatment of Ovarian germ cell cancer:

• BEP regimen:
  • 30 units/dose intravenous on days 1, 8, and 15 of a 21-day treatment cycle for 3 cycles in combination with etoposide and cisplatin or
  • 15 units/m² on day 1 of a 21-day treatment cycle for 4 cycles in combination with etoposide and cisplatin.

Bleomycin Dose in Children:

Note: 1 USP unit = 1 mg = 1,000 international units.

Use as Test dose for lymphoma patients: Limited data available:

• Test dose for lymphoma patients:

A small amount (2 units or less) of the medicine may be given as a test before the first full dose to check for any allergic reactions. The patient should be closely monitored for 15 minutes after the test dose and then at least once every hour before giving the rest of the dose.

If there are no reactions, a regular dose can be given. It's important to continue monitoring the patient even after the first two doses, as the test dose may not always accurately predict any potential reactions

Use in the treatment of Hodgkin lymphoma as a combination regimen: 

• ABVE-PC regimen in patients with an intermediate-risk or high-risk Hodgkin lymphoma:
  • 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.
• ABVD regimen for high-risk Hodgkin lymphoma:
  • 10 units/m² intravenous on days 1 and 15 of a 28-day treatment cycle for 2 to 6 cycles in combination with doxorubicin, vinblastine, and dacarbazine.
• BEACOPP regimen for high-risk Hodgkin lymphoma:
  • 10 units/m² intravenous on day 7 of a 21-day treatment cycle for 2 - 4 cycles in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

Use in the treatment of Malignant germ cell cancer:

• PEB regimen:
  • Infants: 5 mg/kg intravenous on day 1 of a 21-day treatment cycle for 4 cycles in combination with cisplatin and etoposide
  • Children and Adolescents: 15 units/m² intravenous on day 1 of a 21-day treatment cycle for 4 cycles in combination with cisplatin and etoposide.

Pregnancy Risk Factor D

As per the manufacturer's instructions, it should not be used in pregnant women. If chemotherapy is needed, it should be avoided during the first trimester of pregnancy.

There should be a gap of at least three weeks between the last dose of chemotherapy and the expected delivery date. After 33 weeks of pregnancy, chemotherapy should not be given. Bleomycin may be used in the treatment of Hodgkin's lymphoma as part of a multiagent therapy (ABVD) when required.

Use during breastfeeding:

It is unknown if the drug is excreted into breast milk or not. The manufacturer recommends that you stop breastfeeding while on bleomycin therapy.

Bleomycin Dose in Renal Disease:

Bleomycin dose in patients with kidney disease (As per the manufacturer's labeling):

• CrCl of 50 mL/minute or more:
  • Continue the usual recommended dose.
• CrCl 40 - 50 mL/minute:
  • Reduce the dose by 70% of the normal dose.
• CrCl 30 - 40 mL/minute:
  • Reduce the dose to 60% of the normal dose
• CrCl 20 -  30 mL/minute:
  • Reduce the dose to 55% of the normal dose
• CrCl 10 - 20 mL/minute:
  • Reduce the dose to 45% of the normal dose
• CrCl 5 - 10 mL/minute:
  • Reduce the dose to 40% of the normal dose

Adjustment in dose alternative to the manufacturer's labeling is given below:

• Continuous renal replacement therapy (CRRT):
  • Reduce the dose to 75% of the normal dose.
• CrCl of 46 - 60 mL/minute:
  • Reduce the dose to 70% of the normal dose
• CrCl 31 - 45 mL/minute:
  • Reduce the dose to 60% of the normal dose
• CrCl of less than 30 mL/minute:
  • Use an alternative drug.

Bleomycin Dose in Liver Disease:

• Adjustment in the dose has not been recommended by the manufacturer.

Common Side Effects of Bleomycin:

• Cardiovascular:
  • Phlebitis
• Central nervous system:
  • Tumor pain
• Dermatologic:
  • Hyperpigmentation
  • Atrophic Striae
  • Erythema
  • Exfoliation of The Skin
  • Hyperkeratosis
  • Localized Vesiculation
  • Skin Rash
  • Skin Sclerosis
  • Alopecia
  • Nailbed Changes
• Endocrine & metabolic:
  • Weight loss
• Gastrointestinal:
  • Stomatitis
  • Mucositis
  • Anorexia
• Miscellaneous:
  • Febrile reaction

Less Common Side Effects of Bleomycin:

• Dermatologic:
  • Onycholysis
  • Pruritus
  • Thickening of Skin
• Hypersensitivity:
  • Anaphylactoid reaction
• Neuromuscular & skeletal:
  • Diffuse Scleroderma
• Respiratory:
  • Tachypnea
  • Rales
  • Interstitial Pneumonitis
  • Pulmonary Fibrosis
  • Hypoxia

Contraindications to Bleomycin:

• Hypersensitivity to bleomycin and any other component of the formulation

Warnings and Precautions

• Hepatotoxicity

It can cause liver injury manifesting as an elevation in the liver enzymes.

• Reaction idiosyncratic: [US Boxed Warning]:

Idiosyncratic reactions may occur, and they can be severe, leading to symptoms such as low blood pressure, confusion, fever, chills, and wheezing. These reactions typically happen after the first or second dose.

• Toxicity in the lungs: [US Boxed Warning]:

Pulmonary toxicities, such as pulmonary fibrosis or pneumonitis, are serious side effects of bleomycin. Patients who are older than 40 years old, smoke, have a history of radiation therapy, or require oxygen in excess of 400 units per day are at higher risk.

Other pulmonary manifestations like Bronchiolitis Obliterans and Organizational pneumonia (BOOP), eosinophilic hypersensitivity, and interstitial pneumonia that may progress to pulmonary fibrosis can also occur.

Close monitoring for pulmonary toxicity is important, and treatment may need to be stopped if the DLCO (diffusing capacity of the lungs for carbon monoxide) drops by 25%.

• Nephrotoxicity:

It can cause renal impairment. Adjustment may be required for patients with a CrCl below 50 ml/minute.

Bleomycin: Drug Interaction

Risk Factor C Interactions: Monitor Therapy

Risk Factor D: Modify Therapy

Risk Factor: X (Avoid the following medicines in combination with Bleomycin):

Monitor:

• Pulmonary function tests that include:

  • Total lung volume
  • Forced vital capacity (FVC)
  • Diffusion capacity for carbon monoxide (DLCO)
  • Vital capacity
  • Total lung capacity
  • Pulmonary capillary blood volume.
• Chest x-ray
• Renal function
• Liver function tests
• Observe for clinical features of hypersensitivity
• Temperature
• Check body weight at regular intervals.

How to administer Bleomycin?

Monitoring for Lymphoma Patients: Monitor for hypersensitivity reactions, especially after the first 2 doses.

Mechanism of action of Bleomycin:

Bleomycin binds DNA and blocks its synthesis through single- and double-stranded breakages. It inhibits protein and RNA synthesis.

International Brands of Bleomycin:

• Bemocin
• Bileco
• Blenamax
• Blenoxane
• Bleo
• Bleocin
• Bleocina
• Bleocip
• Bleocris
• Bleolem
• Bleomax
• Bleomedac
• Bleomicina
• Bleomycin
• Bleomycin PFI
• Bleomycinum
• Blexit
• Blkesol
• Bloicin-S
• Lyoble
• Naprobleo
• Naproplat

Bleomycin injection in Pakistan: