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|Bleomycin Sulfate

Bleomycin Sulfate

Trade Names:
Blenoxane
- Sterile powder for Injection 15 unit vial (15 units = 15 mg)
- Sterile powder for Injection 30 unit vial (30 units = 30 mg)

Mechanism of Action

Pharmacology

Bleomycin sulfate is a mixture of cytotoxic glycopeptide antibiotics. It inhibits DNA synthesis. When administered intrapleurally, bleomycin acts as a sclerosing agent.

Pharmacokinetics

Distribution

High concentrations are found in the skin and lungs; low concentrations are found in bone marrow.

Elimination

The t _½ is about 115 min; 60% to 70% is excreted in urine as active bleomycin.

Special Populations

In those with Ccr less than 35 mL/min, the t _½ increases.

Indications and Usage

Lymphomas (Hodgkin and non-Hodgkin); testicular carcinoma (eg, embryonal cell, choriocarcinoma, teratocarcinoma); sclerosis of malignant pleural effusions (eg, treatment, prevention); treatment of squamous cell carcinomas (eg, head, neck).

Unlabeled Uses

Mycosis fungoides, osteosarcoma, AIDS-related Kaposi sarcoma.

Contraindications

Standard considerations.

Dosage and Administration

IV / IM / Subcutaneous Because of the possibility of anaphylactoid reaction, treat lymphoma patents with 2 units or less for the first 2 doses. If no acute reaction occurs, follow the regular dosage schedule.

IV / IM / Subcutaneous 10 to 20 units/m ² 1 or 2 times/wk. After a 50% regression of tumor size, a maintenance dose of 1 unit/day or 5 units/wk can be given IV or IM. Response is usually seen within 2 wk. To minimize the risk of pulmonary toxicity, the max cumulative dose should not exceed 400 units. When bleomycin is used in combination with other antineoplastic agents, pulmonary toxicities may occur at lower doses.

Thoracostomy tube 60 units diluted with 50 to 100 mL sodium chloride 0.9% is instilled into chest via a thoracotomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The amount of drainage from the chest tube should be as minimal as possible prior to installation of bleomycin. The thoracotomy tube is then clamped. The patient is moved from the supine to the left and right lateral positions several times during the next 4 h. The clamp is then removed and suction re-established. It is generally accepted that chest tube drainage should be below 100 mL in a 24-h period prior to sclerosis. However, bleomycin instillation may be appropriate when drainage is between 100 and 300 mL under clinical conditions that necessitate sclerosis therapy.

IV / IM / Subcutaneous 10 to 20 units/m ² 1 or 2 times/wk. Response is usually seen within 3 wk. Squamous cell cancers respond more slowly, sometimes requiring 3 wk for improvement and testicular tumors is noticed within 2 weeks.

General Advice

• Diligently follow institutional and NIH procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering bleomycin. Avoid exposure by direct contact of the skin, mucous membranes, and eyes.
• If accidental skin or mucus membrane contact occurs, wash thoroughly with soap and water. If accidental eye contact occurs, immediately institute standard irrigation techniques.
• Do not reconstitute or dilute bleomycin with dextrose 5% in water or any other dextrose-containing diluent. Loss of bleomycin potency will occur.
• For subcutaneous or IM administration, reconstitute powder for injection with sterile water for injection, sodium chloride 0.9% injection, or bacteriostatic water for injection. Reconstitute 15 unit vial with 1 to 5 mL of diluent; reconstitute 30 unit vial with 2 to 10 mL of diluent.
• For IV administration, reconstitute powder for injection with sodium chloride 0.9% injection. Reconstitute 15 unit vial with 5 mL of diluent; reconstitute 30 unit vial with 10 mL of diluent. Infuse prescribed dose slowly over 10 min.
• For intrapleural administration, dissolve 60 units of bleomycin in 50 to 100 mL sodium chloride 0.9% injection. Clamp thoracostomy tube after instilling bleomycin. Move patient from supine to left and right lateral positions several times over next 4 h, then remove clamp and reestablish suction.
• Do not administer if particulate matter or cloudiness is noted.

Storage/Stability

Store powder for injection in refrigerator (36° to 46°F). Bleomycin is stable for 24 h at room temperature when reconstituted with sodium chloride 0.9% injection. Discard any unused solution. Do not save any unused solution for future use.

Drug Interactions

Bleomycin may decrease serum concentrations of digoxin and phenytoin.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension; cerebral arteritis, cerebrovascular accidents, MI, thrombotic microangiopathy, Raynaud phenomenon (with combination chemotherapy).

CNS

Malaise (postmarketing).

Dermatologic

Alopecia, erythema, hyperkeratosis, hyperpigmentation, nail changes, pruritus, rash, skin tenderness, stomatitis, striae, vesiculation (approximately 50%); scleroderma-like skin changes (postmarketing).

GI

Vomiting; anorexia.

Local

Pain; pain at tumor site; phlebitis.

Metabolic-Nutritional

Weight loss (common).

Pulmonary

Pneumonitis, pulmonary fibrosis, dyspnea, rales.

Miscellaneous

Idiosyncratic reaction including chills, fever, hypotension, mental confusion, and wheezing (about 1% of lymphoma patients); chills; fever; acute chest pain.

Precautions

Pregnancy

Category D .

Lactation

Undetermined. It is recommended that breast-feeding be discontinued by women receiving therapy.

Children

Safety and efficacy not established.

Elderly

Pulmonary toxicity was more common in patients older than 70 years of age.

Hypersensitivity

Because of the risk of anaphylactoid-like reactions (ie, hypotension, mental confusion, fever, chills, and wheezing) in lymphoma patient, ensure that lymphoma patient receives no more than 2 units of bleomycin for the first 2 doses. Frequently monitor patient during and after therapy. Be prepared to treat reactions symptomatically. Regular dosing schedule can be followed if no acute reactions occur after either dose.

Renal Function

Patients with a Ccr of less than 35 mL/min should receive a reduced dose of bleomycin. Guidelines for dosage reduction are empiric. Renal toxicity has occurred infrequently. This toxicity may occur at any time.

Hepatic Function

Hepatic toxicity has occurred infrequently. This toxicity may occur at any time.

Death

Death has been rarely reported in association with bleomycin pleurodesis in very seriously ill patients.

Extravasation

Local irritation or phlebitis may occur. Refer to your institution specific protocol.

Skin toxicity

Skin toxicity, a relatively late manifestation, appears to be related to the cumulative dose. It usually develops in the second and third week of treatment after administration of 150 to 200 units of the drug.

Surgical intervention

If patient is to undergo surgical intervention, ensure that surgical team (including anesthesiologist) is aware of treatment with bleomycin and that FI O ₂ should be maintained, if possible, at concentrations no greater than 25%. Fluid replacement should consist of colloids rather than crystalloids to reduce the risk of lung damage.

Patient Information

• Review the treatment regimen including dosing schedule, duration of treatment, and monitoring that will be required.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care professional in a health care setting.
• Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve max benefit possible.
• Advise patient, family, or caregiver that medication may cause hair loss but that this is reversible when therapy is stopped.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing or unexplained shortness of breath; chest pain; fever, chills, or other signs of infection; sores in mouth; pain, redness, or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, or appetite loss; persistent or worsening general body weakness; skin changes; nail changes.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.
• Advise patient that frequent follow-up visits, laboratory tests, x-rays, and breathing tests will be required to monitor therapy, and to keep appointments.