Clinical medicine profile
Bleomycin
Therapeutic agent (verify pharmacological class)
- Route
- INTRAMUSCULAR, INTRAPLEURAL, INTRAVENOUS, SUBCUTANEOUS
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
WARNING It is recommended that Bleomycin for Injection, USP 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 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 greater than 400 units total dose, but pulmonary toxicity has been observed in young patients and those treated with low doses. 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.
Contraindications
- Hypersensitivity to the active substance or excipients.
- Additional absolute contraindications are indication- and product-specific — consult SmPC.
Precautions
- WARNINGS Patients receiving bleomycin must be observed carefully and frequently during and after therapy.
- It should be used with extreme caution in patients with significant impairment of renal function or compromised pulmonary function.
- Pulmonary toxicities occur in 10% of treated patients.
- In approximately 1%, the nonspecific pneumonitis induced by bleomycin progresses to pulmonary fibrosis and death.
- Although this is age and dose related, the toxicity is unpredictable.
- Frequent roentgenograms are recommended (see ADVERSE REACTIONS: Pulmonary ).
- A severe idiosyncratic reaction (similar to anaphylaxis) consisting of hypotension, mental confusion, fever, chills, and wheezing has been reported in approximately 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 (see ADVERSE REACTIONS: Idiosyncratic Reactions ).
- Renal or hepatic toxicity, beginning as a deterioration in renal or liver function tests, have been reported.
- These toxicities may occur at any time after initiation of therapy.
- Usage in Pregnancy Pregnancy “Category D” Bleomycin can cause fetal harm when administered to a pregnant woman.
- It has been shown to be teratogenic in rats.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION Because of the possibility of an anaphylactoid reaction, lymphoma patients should be treated with 2 units or less for the first 2 doses. If no acute reaction occurs, then the regular dosage schedule may be followed. The following dose schedule is recommended: Squamous cell carcinoma, non-Hodgkin's lymphoma, testicular carcinoma – 0.25 to 0.50 units/kg (10 to 20 units/m 2 ) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. Hodgkin's Disease – 0.25 to 0.50 units/kg (10 to 20 units/m 2 ) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. After a 50% response, a maintenance dose of 1 unit daily or 5 units weekly intravenously or intramuscularly should be given. Pulmonary toxicity of bleomycin for injection appears to be dose-related with a striking increase when the total dose is over 400 units. Total doses over 400 units should be given with great caution. Note: When bleomycin for injection is used in combination with other antineoplastic agents, pulmonary toxicities may occur at lower doses. Improvement of Hodgkin's disease and testicular tumors is prompt and noted within 2 weeks. If no improvement is seen by this time, improvement is unlikely. Squamous cell cancers respond more slowly, sometimes requiring as long as 3 weeks before any improvement is noted. Malignant Pleural Effusion – 60 units administered as a single dose bolus intrapleural injection (see ADMINISTRATION: Intrapleural ). Use in Patients with Renal Insufficiency The following dosing reductions are proposed for patients with creatinine clearance (CrCL) values of less than 50 mL/min: CrCL can be estimated from the individual patient's measured serum creatinine (Scr) values using the Cockcroft and Gault formula: Males CrCL = [weight × (140 – Age)]/(72 × Scr) Females CrCL = 0.85 × [weight × (140 – Age)]/(72 × Scr) Where CrCL in mL/min/1.73m 2 , weight in kg, age in years, and Scr in mg/dL. Patient CrCL (mL/min) Bleomycin for Injection Dose (%) 50 and above 100 40 to 50 70 30 to 40 60 20 to 30 55 10 to 20 45 5 to 10 40
Pediatric Use Safety and effectiveness of bleomycin in pediatric patients have not been established.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE Bleomycin for Injection, USP should be considered a palliative treatment.
- It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents: Squamous Cell Carcinoma: Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva.
- The response to Bleomycin for Injection, USP is poorer in patients with previously irradiated head and neck cancer.
- Lymphomas: Hodgkin's disease, non-Hodgkin's lymphoma.
- Testicular Carcinoma: Embryonal cell, choriocarcinoma, and teratocarcinoma.
- Bleomycin for Injection, USP has also been shown to be useful in the management of: Malignant Pleural Effusion: Bleomycin for Injection, USP is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions.
Adverse effects
- ADVERSE REACTIONS Pulmonary The most serious side effects are pulmonary adverse reactions, occurring in approximately 10% of treated patients.
- The most frequent presentation is pneumonitis occasionally progressing to pulmonary fibrosis.
- Approximately 1% of patients treated have died of pulmonary fibrosis.
- Pulmonary toxicity is both dose and age related, being more common in patients over 70 years of age and in those receiving over 400 units total dose.
- This toxicity, however, is unpredictable and has been seen in young patients receiving low doses.
- Some published reports have suggested that the risk of pulmonary toxicity may be increased when bleomycin is used in combination with G-CSF (filgrastim) or other cytokines.
- However, randomized clinical studies completed to date have not demonstrated an increased risk of pulmonary complications in patients treated with bleomycin and G-CSF.
- Because of lack of specificity of the clinical syndrome, the identification of patients with pulmonary toxicity due to bleomycin has been extremely difficult.
- The earliest symptom associated with bleomycin pulmonary toxicity is dyspnea.
- The earliest sign is fine rales.
- Radiographically, bleomycin-induced pneumonitis produces nonspecific patchy opacities, usually of the lower lung fields.
- The most common changes in pulmonary function tests are a decrease in total lung volume and a decrease in vital capacity.
- However, these changes are not predictive of the development of pulmonary fibrosis.
- The microscopic tissue changes due to bleomycin toxicity include bronchiolar squamous metaplasia, reactive macrophages, atypical alveolar epithelial cells, fibrinous edema, and interstitial fibrosis.
Drug interactions
Open multi-drug checker ↗- This is a cytotoxic agent that causes little bone marrow suppression.
- It is a mixture of glycopeptide antibiotics isolated from a strain of Streptomyces verticillus.
- It is used either as a single agent or in proven combinations with other approved chemotherapeutic agents.
Mechanism & disposition
Mechanism of Action Although the exact mechanism of action of bleomycin is unknown, available evidence indicates that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA and protein synthesis.
Read complete mechanism
Mechanism of Action Although the exact mechanism of action of bleomycin is unknown, available evidence indicates that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA and protein synthesis. Bleomycin is known to cause single, and to a lesser extent, double-stranded breaks in DNA. In in vitro and in vivo experiments, bleomycin has been shown to cause cell cycle arrest in G2 and in mitosis. When administered into the pleural cavity in the treatment of malignant pleural effusion, bleomycin acts as a sclerosing agent.
Product-specific
Product-specific
INTRAMUSCULAR, INTRAPLEURAL, INTRAVENOUS, SUBCUTANEOUS
Bleomycin is rapidly absorbed following either intramuscular, subcutaneous, intraperitoneal, or intrapleural administration reaching peak plasma concentrations in 30 to 60 minutes. Systemic bioavailability of bleomycin is 100% and 70% following intramuscular and subcutaneous admi...
Bleomycin is widely distributed throughout the body with a mean volume of distribution of 17.5 L/m 2 in patients following a 15 units/m 2 intravenous bolus dose. Protein binding of bleomycin has not been studied.
Bleomycin is inactivated by a cytosolic cysteine proteinase enzyme, bleomycin hydrolase. The enzyme is widely distributed in normal tissues with the exception of the skin and lungs, both targets of bleomycin toxicity. Systemic
of the drug by enzymatic degradation is probably only important in patients with severely compromised renal function. Excretion The primary route of elimination is via the kidneys. About 65% of the administered intravenous dose is excreted in urine within 24 hours. In patients wi...
of 2 hours following intravenous bolus administration. Total body clearance and renal clearance averaged 51 mL/min/m 2 and 23 mL/min/m 2 , respectively. Following intrapleural administration to patients with normal renal function, a lower percentage of drug (40%) is recovered in...
Pregnancy, lactation & diet
Use only if potential benefit justifies potential risk; prefer agents with better reproductive data when alternatives exist.
Nursing Mothers It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued by women receiving bleomycin therapy.
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| Bleocip | Cipla | 15mg 1's | Unavailable |
| Bleocip | Cipla | tabs 15mg 5mL | Unavailable |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.