Blenoxane

Other Cytotoxic Antibiotics

NOTE: A unit of bleomycin is equal to the formerly used milligram activity (i.e., 1 unit = 1 mg). The term milligram activity is a misnomer and has been changed to units to be more precise.
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Minimal
Extravasation Risk
Nonvesicant

Bleomycin is administered intramuscularly, subcutaneously, intravenously, intrapleurally, intralesionally, or intraarterially.
Premedication with acetaminophen may decrease the incidence of fever and chills following bleomycin administration.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Reconstitution:
Reconstitute 15 or 30 unit vial with 5 mL or 10 mL 0.9% Sodium Chloride for injection, respectively.
Do not use dextrose containing solutions for reconstitution or further dilution due to a loss of potency.
Maximum concentration should be bleomycin 5 units/mL.
Bleomycin reconstituted with 0.9% Sodium Chloride for injection is stable for 24 hours at room temperature.
 
Intravenous injection or infusion:
After reconstitution, inject slowly over a period of 10 minutes.
Alternatively, after reconstitution, further dilute bleomycin in 50 ml NS and inject IV slowly over 10—15 minutes.

Reconstitution:
Reconstitute 15 unit vial with 1—5 mL of sterile water for injection, 0.9% sodium chloride for injection, or bacteriostatic water for injection, or reconstitute 30 unit vial with 2—10 mL sterile water for injection, 0.9% sodium chloride for injection, or bacteriostatic water for injection.
Do not use dextrose containing solutions for reconstitution or further dilution due to a loss of potency.
Maximum concentration should be bleomycin 5 units/mL.
Bleomycin reconstituted with 0.9% sodium chloride for injection is stable for 24 hours at room temperature.
Intramuscular injection:
Inject into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel.

Reconstitution:
Reconstitute 15 unit vial with 1—5 mL of sterile water for injection, 0.9% Sodium Chloride for injection, or bacteriostatic water for injection, or reconstitute 30 unit vial with 2—10 mL sterile water for injection, 0.9% Sodium Chloride for injection, or bacteriostatic water for injection.
Do not use dextrose containing solutions for reconstitution or further dilution due to a loss of potency.
Maximum concentration should be bleomycin 5 units/mL.
Bleomycin reconstituted with 0.9% Sodium Chloride for injection is stable for 24 hours at room temperature.
 
Subcutaneous injection:
Avoid intradermal injections when bleomycin is administered subcutaneously.

Intrapleural instillation:
Dissolve 60 units in 50—100 mL 0.9% Sodium Chloride for injection.
Administer through a thoracostomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The thoracostomy tube is clamped after instillation of the bleomycin. The patient should be moved from the supine to the left and right lateral positions several times over the next four hours. Afterwards, the clamp is removed and suction reestablished.
 
Intraarterial infusion:
NOTE: Bleomycin is not approved by the FDA for intraarterial infusion.
Following reconstitution, further dilute bleomycin in 50 mL 0.9% Sodium Chloride for injection.
Inject intraarterially slowly over 10—15 minutes.
 
Intralesional injection:
NOTE: Bleomycin is not approved by the FDA for intralesional injection.
Inject into the lesion or place on lesion and prick lesion using a Monolet needle.
Typically, bleomycin is further diluted to a 0.4—2 unit per mL solution.
Bleomycin intralesional use may be reconstituted with lidocaine to decrease pain on administration.

pulmonary fibrosis / Delayed / 2.0-3.0
serious hypersensitivity reactions or anaphylaxis / Rapid / 0-1.0
pulmonary toxicity / Early / Incidence not known
pericarditis / Delayed / Incidence not known
hemolytic-uremic syndrome / Delayed / Incidence not known
thrombotic microangiopathy / Delayed / Incidence not known
stroke / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known

pneumonitis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hyperesthesia / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
erythema / Early / Incidence not known
hypotension / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
confusion / Early / Incidence not known
phlebitis / Rapid / Incidence not known

fever / Early / 60.0
alopecia / Delayed / Incidence not known
rash / Early / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
nail discoloration / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
hyperkeratosis / Delayed / Incidence not known
striae / Delayed / Incidence not known
chills / Rapid / Incidence not known
malaise / Early / Incidence not known
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
weight loss / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known

Serious hypersensitivity reactions or anaphylaxis may occur with bleomycin. It is contraindicated in patients who have demonstrated bleomycin hypersensitivity or have experienced a hypersensitivity or idiosyncratic reaction to bleomycin (e.g., hypotension, mental confusion, fever, chills, and wheezing). Bleomycin therapy requires an experienced clinician knowledgeable in the use of cancer chemotherapeutic agents. Administration of bleomycin requires a specialized care setting. Because of the possibility of an anaphylactoid or hypersensitivity reaction, lymphoma (i.e., Hodgkin's disease or non-Hodgkin's lymphoma) patients should receive a test dose of bleomycin. The bleomycin test dose consisting of 2 units or less can be given by the IM, IV, or subcutaneous routes. It is recommended that the patient be observed for 24 hours after the test dose. Observational periods of less than 24 hours have been used based on the observation that most patients who are going to react do so within the first two hours after administration. However, a 24-hour observational period may increase the predictive value for a delayed reaction.

Patients should be monitored closely for bleomycin-induced pulmonary toxicity; patients with preexisting pulmonary fibrosis or other pulmonary disease may be at increased risk. The occurrence of bleomycin-induced pulmonary toxicity is unpredictable, but occurs more frequently in geriatric patients and in those receiving more than 400 units cumulative dose of bleomycin (maximum cumulative lifetime dose). However, pulmonary toxicity has been observed in younger patients and in those treated with low doses. In addition, when bleomycin is used with other antineoplastic agents, pulmonary toxicities can occur at lower doses. Frequent roentgenograms are recommended during bleomycin therapy. Studies have suggested that sequential measurement of the pulmonary diffusion capacity for carbon monoxide (DLCO) during bleomycin treatment may be an indicator of subclinical pulmonary toxicity. It is recommended that the DLCO be monitored monthly if it is to be used to detect pulmonary toxicity, and bleomycin treatment be stopped when the DLCO falls below 40% of the pretreatment value. Bleomycin should be used cautiously in patients who have had previous or concurrent thoracic radiation therapy or in patients who are currently or have had a history of tobacco smoking due to an increased risk of pulmonary toxicity. Patients with infectious pneumonitis should be treated immediately. Patients with a pulmonary infection should be treated prior to initiation of bleomycin therapy.

Blenoxane

Rx

Antibiotic antineoplastic
Mixture of 13 glycopeptides; active component is the A-2 peptide
Used for Hodgkin lymphoma, NHL, testicular cancer, squamous cell cancer of the head and neck and cervix, and malignant pleural effusions.

5 units/m2 IV on weeks 2, 4, 6, 8, 10, and 12 in combination with mechlorethamine (6 mg/m2 IV on weeks 1, 5, and 9), doxorubicin (25 mg/m2 IV on weeks 1, 3, 5, 7, 9, and 11), vinblastine (6 mg/m2 IV on weeks 1, 3, 5, 7, 9, and 11), vincristine (1.4 mg/m2 [Max: 2 mg] IV on weeks 2, 4, 6, 8, 10, and 12), etoposide (60 mg/m2/day IV on 2 consecutive days in weeks 3, 7, and 11), and prednisone (40 mg/m2 PO every other day for 10 weeks then tapered by 10 mg PO every other day between weeks 10 and 12). Total duration of Stanford V regimen is 12 weeks (three 4-week cycles). Doses of mechlorethamine, doxorubicin, vinblastine, and etoposide have been reduced to 65% if ANC < 1000/mm3 (treatment delayed if ANC < 500/mm3). Prophylactic sulfamethoxazole-trimethoprim, acyclovir, and ranitidine were given throughout the treatment period. G-CSF has also been used to maintain dose intensity as needed after the first dose reduction. Alternative prophylactic medications have also been used.

10 units/m2 IV on day 8 in combination with etoposide (100 mg/m2/day IV on days 1—3), doxorubicin (25 mg/m2 IV on day 1), cyclophosphamide (650 mg/m2 IV on day 1), vincristine (1.4 mg/m2 [Max: 2 mg] IV on day 8), procarbazine (100 mg/m2/day PO on days 1—7), and prednisone (40 mg/m2 PO on days 1—14). Cycles are repeated every 21 days for up to 8 cycles. Filgrastim was administered beginning on day 8 of each cycle and continued until the leukocyte count returned to normal in some clinical trials. The escalated dose BEACOPP regimen includes bleomycin 10 units/m2 IV on day 8 in combination with etoposide (200 mg/m2/day IV on days 1—3), doxorubicin (35 mg/m2 IV on day 1), cyclophosphamide (1200 mg/m2 IV on day 1), vincristine (1.4 mg/m2 [Max: 2 mg] IV on day 8), procarbazine (100 mg/m2/day PO on days 1—7), and prednisone (40 mg/m2 PO on days 1—14). Cycles are repeated every 21 days for up to 8 cycles. Filgrastim was administered beginning on day 8 of each cycle and continued until the leukocyte count returned to normal in some clinical trials.The standard dose BEACOPP and escalated dose BEACOPP regimens have shown benefit for the treatment of advanced Hodgkin lymphoma in clinical trials. Escalated dose BEACOPP has shown a significantly better freedom from treatment failure at 10 years (82% vs. 70%, p < 0.0001) and overall survival at 10 years (86% vs. 80%, p = 0.0053) compared to standard dose BEACOPP. A regimen of 4 cycles of escalated dose BEACOPP followed by 4 cycles of standard dose BEACOPP has also been used in patients who achieve a complete response after the initial 4 cycles of escalated dose BEACOPP.

If given as a single agent, 5—20 units/m2 (0.25—0.5 units/kg) IV, IM or subcutaneous, administered 1 or 2 times/week. When used as part of ABVD (doxorubicin, vinblastine, and dacarbazine), bleomycin is given in a dose of 10 units/m2 IV. After a 50% response, a maintenance dose of 1 unit daily or 5 units weekly IV, IM, or subcutaneous should be given. Improvement is usually prompt and noted within 2 weeks. If no improvement is seen by this time, benefits are unlikely.

Because of the possibility of an anaphylactoid reaction, lymphoma patients are usually given 2 units or less IV, IM, or subcutaneous for the first 2 doses or as a test dose, followed by a 24-hour observation. If no acute reactions occur, the regular doses may be given.

If given as a single agent, 10—20 units/m2 (0.25—0.5 units/kg) IV, IM or subcutaneous, administered 1 or 2 times/week. Other treatment regimens also include bleomycin with the dose varying from regimen to regimen. In CHOP-Bleo, a fixed single dose of 15 units IV is given on days 1 and 5 with cyclophosphamide, doxorubicin, vincristine, and prednisone. In m-BACOD, the dose of bleomycin is 4 units/m2 IV on day 1.

5—20 units/m2 (0.25—0.5 units/kg) IV, IM, or subcutaneous, administered 1 or 2 times/week. Because squamous cell carcinomas usually respond slower, improvements may not be noted for as long as 3 weeks. The response to bleomycin is poorer in patients with previously irradiated head and neck cancer.

Bleomycin in doses up to 60 units/day have been given intraarterially to provide increased local concentrations in the treatment of squamous cell carcinoma of the cervix and head and neck cancer.

30 units IV on days 1, 8, and 15, in combination with cisplatin and etoposide, every 21 days for 3 cycles. In a randomized clinical trial, treatment with BEP resulted in a response rate of 94% of patients with disseminated germ cell tumors compared with 88% for those treated with etoposide plus cisplatin. In a randomized clinical trial of patients with favorable-prognosis germ-cell cancer, there was not a significant difference between 3 cycles of BEP and 4 cycles in terms of overall or disease-free survival.

10 units/m2 IV on days 1 and 8 in combination with cisplatin 75 mg /m2 IV on day 1 and methotrexate 25 mg/m2 IV bolus on days 1 and 8, repeated every 21 days. Treatment was given for 6 cycles if a complete remission was achieved. Patients who achieved stable disease or a partial response, continued treatment until disease progression. Bleomycin was discontinued after a maximum cumulative dose of 200 units/m2 was given.

10—20 units/m2 (0.25—0.5 units/kg) IV, IM, or subcutaneous, administered 1 or 2 times per week. Because squamous cell carcinomas usually respond slower, improvements may not be noted for as long as 3 weeks.

60 units administered as a single bolus intrapleural injection.

15 units/m2/day IV on days 1 and 2 or on days 1, 2, and 3 in combination with cyclophosphamide and dactinomycin (BCD regimen) has been incorporated into multiple treatment protocols for osteogenic sarcoma. In the POG-8651 protocol, 106 patients (< 30 years old) with previously untreated nonmetastatic high-grade osteogenic sarcoma were randomized to receive 3 days of BCD each cycle as part of a multiagent chemotherapy regimen in sequence with doxorubicin and cisplatin, and high-dose methotrexate, either before or after surgical resection. Event-free survival (EFS), the primary endpoint, was not significantly different between the treatment arms, and reached 69% at 5 years in the post-operative group. In a comparison of the Memorial Sloan-Kettering Cancer Center T-10 and T-12 protocols, 73 patients (ages 4.6—36.4 years) with previously untreated, high-grade osteogenic sarcoma received BCD on days 1 and 2 of each cycle as part of a multiagent chemotherapy regimen in sequence with doxorubicin and cisplatin, high-dose methotrexate, and surgical resection. The 5-year EFS was 78% and 73% in the T-12 and T-10 protocols, respectively. The use of BCD alone has also been studied in 8 pediatric patients (ages 9.1—16.4 years) with previously treated metastatic osteogenic sarcoma. Patients received 1—5 courses of BCD. No tumor regression could be measured for any of the patients, and progressive tumor enlargement was demonstrated in 2 patients.

15 units IV on day 1 in combination with doxorubicin (10 mg/m2 IV on day 1) and vincristine (1 mg IV on day 1), repeated every 2 weeks. Alternately, bleomycin 10 mg/m2 IV on day 1 has been given in combination with doxorubicin (20 mg/m2 IV on day 1) and vincristine (1 mg IV on day 1), repeated every 2 weeks for 6 cycles.

150 units mixed in 2 L 1.5% warmed dineal solution via peritoneal dialysis catheter for 4 hours has been studied with some success in a small clinical trial (n = 10).

Typically, 1 mL of bleomycin 1 unit/mL solution is injected into the lesion every 2 weeks. Alternatively, bleomycin 1 unit/mL solution may be dropped onto the lesion and pricked into the wart using a needle. Patients who do not respond to 3 injections are usually considered treatment failures. Premedication with a topical local anesthetic is recommended to decrease pain on injection. Alternatively, a single dose of 0.5 mg/mL solution with 2% lidocaine injected into the lesion using an insulin syringe has been used. NOTE: 1 unit = 1 mg. Response rates to bleomycin range from 33—92%.

A single dose of 0.5 mg/mL solution with 2% lidocaine injected into the lesion using an insulin syringe has been used. NOTE: 1 unit = 1 mg.

Bleomycin has been used via intravesical injection for the treatment of hemangiomas. In one report, 5 patients age 5—19 years with massive inoperable hemangiomas were treated with intralesional injections of 2 units bleomycin as a 0.4 unit/mL solution. The injections were repeated after 4—6 weeks for a total of 6—10 treatments. Pain relief and decreased swelling was noted in all cases. In a similar report, bleomycin injections of 0.5—2 units/mL were used for a total dose of 0.3—0.6 units/kg per treatment session every 6 weeks for up to 3 sessions. Lesions regressed 60—100% during 6—14 months following bleomycin injections; the lesions of 3 patients were completely excised after 1 bleomycin injection.

†Indicates off-label use

No dosage adjustment required.

CrCl 40—50 mL/min: reduce bleomycin dose by 30%.
CrCl 30—39 mL/min: reduce bleomycin dose by 40%.
CrCl 20—29 mL/min: reduce bleomycin dose by 45%.
CrCl 10—19 mL/min: reduced bleomycin dose by 55%.
CrCl 5—10 mL/min: reduce bleomycin dose by 60%.
Various recommendations for bleomycin dosage reduction in renal impairment are reported in the literature. Bleomycin is not removed by hemodialysis.

Aminoglycosides: (Moderate) Previous treatment with nephrotoxic agents, like aminoglycosides, may result in decreased clearance of bleomycin if renal function has been impaired.
Brentuximab vedotin: (Contraindicated) Concomitant administration of brentuximab vedotin and bleomycin is contraindicated due to an increased risk for non-infectious pulmonary toxicities. Pulmonary toxicies are a known adverse reaction associated with bleomycin therapy. In studies of chemotherapeutic regimens containing bleomycin (without brentuximab vedotin), some degree of pulmonary toxicity occurs in up to 10% of patients; however, in one study in which bleomycin was administered in combination with brentuximab vedotin, doxorubicin, vinbalstine, and darcarbazine (ABVD), approximately 40% of patients experienced pulmonary toxicities.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cisplatin: (Moderate) Monitor for an increase in bleomycin-related adverse reactions if coadministration with cisplatin is necessary. Bleomycin is primarily eliminated through renal excretion; therefore, its clearance may be affected by nephrotoxic agents such as cisplatin. In one report of 2 children receiving concomitant cisplatin with bleomycin, total body clearance of bleomycin decreased from 39 mL/min/m2 to 18 mL/min/m2 as the cumulative dose of cisplatin exceeded 300 mg/m2; the terminal half-life of bleomycin also increased from 4.4 hours to 6 hours. Fatal bleomycin pulmonary toxicity has been reported in a patient with unrecognized cisplatin-induced oliguric renal failure.
Cyclosporine: (Minor) Previous treatment with nephrotoxic agents, like cyclosporine, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity in patients with concomittant or prior cyclosporine therapy.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Foscarnet: (Minor) Previous treatment with nephrotoxic agents, like foscarnet, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity in patients with concomittant or prior foscarnet therapy.
Hydantoins: (Major) Patients receiving antineoplastic agents concurrently with hydantoins may be at risk for toxicity or loss of clinical efficacy and seizures; anticonvulsant therapy should be monitored closely during and after administration of antineoplastic agents. Concurrent therapy with phenytoin and bleomycin has been associated with subtherapeutic phenytoin serum concentrations and seizure activity. Phenytoin dosage increases of 20 to 100% have been required in some patients, depending on the chemotherapy administered.
Pentamidine: (Moderate) Previous or concurrent treatment with nephrotoxic agents, like pentamidine, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity (e.g., pulmonary toxicity) in patients with concomittant or prior history of systemic pentamidine therapy.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Vancomycin: (Minor) Previous treatment with nephrotoxic agents, like vancomycin, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity in patients with concomittant or prior vancomycin therapy.
Vitamin C: (Moderate) Monitor for decreased efficacy of bleomycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration of ascorbic acid and bleomycin may result in decreased efficacy of bleomycin.

Blenoxane/Bleomycin/Bleomycin Sulfate Intramuscular Inj Pwd F/Sol: 15U, 30U
Blenoxane/Bleomycin/Bleomycin Sulfate Intrapleural Inj Pwd F/Sol: 15U, 30U
Blenoxane/Bleomycin/Bleomycin Sulfate Intravenous Inj Pwd F/Sol: 15U, 30U
Blenoxane/Bleomycin/Bleomycin Sulfate Subcutaneous Inj Pwd F/Sol: 15U, 30U

The suggested maximum tolerated dose (MTD) for bleomycin, which is dependent on performance status, other chemotherapy agents or radiation given in combination, and disease state, is as follows:
 
NOTE: The correct dose of bleomycin will vary from protocol to protocol. Clinicians should consult the appropriate references to verify the dose.

Maximum lifetime cumulative dosage of bleomycin is 400 units intravenous (IV), intramuscular (IM), or subcutaneous.

Maximum lifetime cumulative dosage of bleomycin is 400 units intravenous (IV), intramuscular (IM), or subcutaneous. However, elderly patients may develop pulmonary toxicity at lower cumulative bleomycin doses.

Maximum lifetime cumulative dosage of bleomycin is 400 units intravenous (IV), intramuscular (IM), or subcutaneous.

Maximum lifetime cumulative dosage of bleomycin is 400 units intravenous (IV), intramuscular (IM), or subcutaneous.

Bleomycin exerts its cytotoxic effects by binding directly to DNA. Other potential areas of cytotoxic activity include affects on lipid peroxidation and oxidative degradation of RNA. Bleomycin exerts its effects on DNA through a multi-step process. Initially, an iron (Fe), bleomycin, oxygen complex is formed. This complex is formed in the presence of DNA, which stabilizes it. The binding of the bleomycin complex to DNA occurs at certain nucleotide sequences via electrostatic interactions and partial intercalation of bleomycin. Lastly, the bleomycin complex functions as ferrous oxide during DNA cleavage, resulting in single- and double-strand breaks. Cells are most susceptible to bleomycin in the G2 or M phase of the cell cycle. Although increased toxicity occurs in the G2 phase, it is not clear if bleomycin has preferential activity for rapidly (i.e., logarithmically) dividing cells or non-dividing (i.e., plateau-phase) cells.
 
Factors of resistance to bleomycin include increased drug inactivation, decreased drug accumulation, and increased DNA repair. Bleomycin hydrolase converts bleomycin to an inactive form, and increased levels of this enzyme have been associated with bleomycin resistance. In addition, normal tissues with high levels of this enzyme (e.g., liver, spleen, and bone marrow) are less susceptible to the toxic effects of the drug. As opposed to other natural antineoplastic agents, bleomycin is not affected by P-glycoprotein, which is coded for by the mutidrug resistance 1 (MDR1) gene.

Bleomycin is poorly absorbed across the GI tract and must be administered parenterally.  Bleomycin distributes mainly into the tissues of the skin, lungs, kidneys, peritoneum, and lymphatics. Only 10% of a dose binds to plasma proteins.
 
Bleomycin appears to undergo extensive metabolism by a specific cysteine proteinase, bleomycin hydrolase. Bleomycin hydrolase is found in most tissues except for the lungs and skin, which are the primary sites of bleomycin toxicity. Bleomycin is excreted primarily by the kidneys. Approximately 45—70% of a dose can be recovered in the urine in the first 24 hours. The half-life in patients with normal renal function is 2—4 hours. Bleomycin clearance correlates well with creatinine clearance.

After IV administration, bleomycin distributes to intracellular and extracellular spaces in 10—20 minutes.

After IM administration of bleomycin, peak concentrations are only one-tenth those occurring after IV administration.

Intrapleural Route
Bleomycin may be administered into pleural or peritoneal spaces. Approximately 45% of a dose can be absorbed systemically, but cavitary concentrations are 10—22% higher than the corresponding plasma concentrations. Only 17% of the intrapleural dose is recovered in the urine.

Bleomycin is FDA pregnancy risk category D and can harm the fetus when given during pregnancy. Animal studies reveal abortifacient and/or teratogenic effects. Bleomycin should be given to pregnant women only when the benefit to the mother outweighs the risk to the fetus. Females of childbearing potential should be advised to avoid becoming pregnant while receiving bleomycin. If bleomycin is used during pregnancy or if a patient becomes pregnant while receiving bleomycin, the patient should be made aware of the potential harm to the fetus.

It is not known whether bleomycin is excreted into breast milk. Many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from bleomycin, breast-feeding is not advised, and patients should be instructed to discontinue breast-feeding during bleomycin therapy.