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

• It is used as a sclerosing agent for malignant pleural effusion:

• In the treatment of 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 intrapleurally.

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 Childrens

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 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 patient should be monitored at 15 minutes interval and a minimum of the one-hour interval before administering the remaining dose.
  • 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.

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, 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

• According to the manufacturer's recommendations, it should not be used in pregnant women.
• If chemotherapy is necessary,
• It should not be used during the first trimester.
  • Between the last dose of chemotherapy and the expected delivery date, there should be at least three weeks.
  • After 33 weeks gestation, chemotherapy should not be given.
• Bleomycin can be used in the treatment of Hodgkin’s lymphoma when multiagent therapy (a component of ABVD), is required.

Bleomycin

• It is unknown if the drug can be absorbed into breastmilk.
• 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:
  • Adjustment  in the dosage is not necessary.
• 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 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 Include:

• 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 Include:

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

Contraindication to Bleomycin include:

• Hypersensitivity to bleomycin and any other component of the formulation

Warnings and Precautions

• Hepatotoxicity
  • It can be hepatotoxic, and could cause liver enzyme elevations.
• Reaction idiosyncratic: [US Boxed Warning]
  • It is possible to experience idiosyncratic reactions. 
  • These reactions can be severe enough that they can cause hypotension, mental chaos, fever, chills and wheezing.
  • These reactions usually occur within the first or second dose.
• Toxicity in the lungs: [US Boxed Warning]
  • Pulmonary toxicities are among the most serious adverse effects of bleomycin.
  • Some patients may develop pulmonary fibrosis or pneumonitis.
  • Patients older than 40 years old, who smoke, or have a history of radiation therapy, are more at risk for developing pulmonary toxicities.
  • Patients who have had to take oxygen in excess of 400 units per day are also at greater risk.
  • Other than pulmonary fibrosis and bleomycin-induced lung toxicities, there are other pulmonary manifestations.
    • Bronchiolitis Obliterans and Organizational pneumonia (BOOP).
    • Eosinophilic hypersensitivity
    • Interstitial pneumonia that can progress to pulmonary Fibrosis.
  • Patients must be closely monitored for pulmonary toxicity. Treatment may be stopped if the DLCO drops by 25%.
• Toxicity in the renal system:
  • It can cause renal impairment. Adjustment may be required for patients with a CrCl below 50 ml/minute.

Bleomycin: Drug Interaction

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?

• Intravenous administration:
  • Intravenous doses should be administered slowly over 10 minutes.
• Intramuscular or Subcutaneous administration:
  • IM injection may cause pain at the injection site.
• Intrapleural administration:
  • 60 units in 50 - 100 mL 0.9% saline is administrered.
  • Concomitant administration of the topical anesthetics or opioid analgesia is usually not required.
• Patients with lymphoma should be monitored for hypersensitivity reactions especially following 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.

It is quickly absorbed by iAdministration intrapleural, subcutaneous, and transmuscular. 

The systemic absorption of serum concentrations following intramuscular, subQ and intrapleural administration is respectively 100%, 70% and 45%. T

he drug's 1% isProtein-boundIt is metabolized in tissues by enzyme activation, except the skin and lungs. TheEliminating half-lifeAfter intravenous administration, it takes 2 hours for the medication to fully absorb.

Time to reach peak serum concentrationThe time taken for intramuscular, intracutaneous and intrapleural administrations is between 30-60 minutes.

ExcretionIt is primarily through urine.

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: