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Medication Safety Issues
Sound-alike/look-alike issues:
Bleomycin may be confused with Cleocin®
Pronunciation
(blee oh MYE sin)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of squamous cell carcinomas, melanomas, sarcomas, testicular carcinoma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma; sclerosing agent for malignant pleural effusion
Pregnancy Risk Factor
D
Pregnancy Considerations
Animal studies have demonstrated teratogenic and abortifacient effects. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should avoid becoming pregnant during treatment.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended.
Contraindications
Hypersensitivity to bleomycin or any component of the formulation; severe pulmonary disease; pregnancy
Warnings/Precautions
Hazardous agent ? use appropriate precautions for handling and disposal. [U.S. Boxed Warnings]: Occurrence of pulmonary fibrosis (commonly presenting as pneumonitis) is higher in elderly patients, patients receiving >400 units total lifetime dose or single doses >30 units, smokers, and patients with prior radiation therapy or receiving concurrent oxygen. A severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing (similar to anaphylaxis) has been reported in 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. Follow manufacturer recommendations for administering O2 during surgery to patients who have received bleomycin. Use caution with renal impairment, may require dose adjustment. May cause renal or hepatic toxicity. [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Safety and efficacy in children have not been established.
Adverse Reactions
>10%:
Dermatologic: Pain at the tumor site, phlebitis. About 50% of patients develop erythema, rash, striae, induration, hyperkeratosis, vesiculation, and peeling of the skin, particularly on the palmar and plantar surfaces of the hands and feet. Hyperpigmentation (50%), alopecia, nailbed changes may also occur. These effects appear dose related and reversible with discontinuation.
Gastrointestinal: Stomatitis and mucositis (30%), anorexia, weight loss
Respiratory: Tachypnea, rales, acute or chronic interstitial pneumonitis, and pulmonary fibrosis (5% to 10%); hypoxia and death (1%). Symptoms include cough, dyspnea, and bilateral pulmonary infiltrates. The pathogenesis is not certain, but may be due to damage of pulmonary, vascular, or connective tissue. Response to steroid therapy is variable and somewhat controversial.
Miscellaneous: Acute febrile reactions (25% to 50%)
1% to 10%:
Dermatologic: Skin thickening, diffuse scleroderma, onycholysis, pruritus
Miscellaneous: Anaphylactoid-like reactions (characterized by hypotension, confusion, fever, chills, and wheezing; onset may be immediate or delayed for several hours); idiosyncratic reactions (1% in lymphoma patients)
<1%: Angioedema, cerebrovascular accident, cerebral arteritis, hepatotoxicity, malaise, MI, nausea, Raynaud's phenomenon, renal toxicity, scleroderma-like skin changes, thrombotic microangiopathy, vomiting; Myelosuppression (rare); Onset: 7 days, Nadir: 14 days, Recovery: 21 days
Drug Interactions
Cisplatin: May decrease bleomycin elimination.
Digitalis glycosides: Bleomycin may decrease plasma levels of digoxin.
Phenytoin: Results in decreased phenytoin levels.
Storage
Refrigerate intact vials of powder; intact vials are stable for up to 1 month at 45°C.
Reconstitution
Reconstitute powder with 1-5 mL BWFI or BNS which is stable at room temperature or under refrigeration for 28 days.
Standard I.V. dilution: Dose/50-1000 mL NS
Compatibility
Stable in NS; variable stability (consult detailed reference) in D5W
Y-site administration: Compatible: Allopurinol, amifostine, aztreonam, cefepime, cisplatin, cyclophosphamide, doxorubicin, doxorubicin liposome, droperidol, etoposide phosphate, filgrastim, fludarabine, fluorouracil, gemcitabine, granisetron, heparin, leucovorin, melphalan, methotrexate, metoclopramide, mitomycin, ondansetron, paclitaxel, piperacillin/tazobactam, sargramostim, teniposide, thiotepa, vinblastine, vincristine, vinorelbine
Compatibility in syringe: Compatible: Cisplatin, cyclophosphamide, doxorubicin, droperidol, fluorouracil, furosemide, heparin, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine
Compatibility when admixed: Compatible: Amikacin, dexamethasone sodium phosphate, diphenhydramine, fluorouracil, gentamicin, heparin, hydrocortisone sodium phosphate, phenytoin, streptomycin, tobramycin, vinblastine, vincristine. Incompatible: Aminophylline, ascorbic acid injection, cefazolin, diazepam, hydrocortisone sodium succinate, methotrexate, mitomycin, nafcillin, penicillin G sodium, terbutaline.
Mechanism of Action
Inhibits synthesis of DNA; binds to DNA leading to single- and double-strand breaks
Pharmacodynamics/Kinetics
Absorption: I.M. and intrapleural administration: 30% to 50% of I.V. serum concentrations; intraperitoneal and SubQ routes produce serum concentrations equal to those of I.V.
Distribution: Vd: 22 L/m2; highest concentrations in skin, kidney, lung, heart tissues; lowest in testes and GI tract; does not cross blood-brain barrier
Protein binding: 1%
Metabolism: Via several tissues including hepatic, GI tract, skin, pulmonary, renal, and serum
Half-life elimination: Biphasic (renal function dependent):
Normal renal function: Initial: 1.3 hours; Terminal: 9 hours
End-stage renal disease: Initial: 2 hours; Terminal: 30 hours
Time to peak, serum: I.M.: Within 30 minutes
Excretion: Urine (50% to 70% as active drug)
Dosage
Maximum cumulative lifetime dose: 400 units; refer to individual protocols; 1 unit = 1 mg
May be administered I.M., I.V., SubQ, or intracavitary
Children and Adults:
Test dose for lymphoma patients: I.M., I.V., SubQ: Because of the possibility of an anaphylactoid reaction, ?2 units of bleomycin for the first 2 doses; monitor vital signs every 15 minutes; wait a minimum of 1 hour before administering remainder of dose; if no acute reaction occurs, then the regular dosage schedule may be followed. Note: Test doses may produce false-negative results.
Single-agent therapy:
I.M./I.V./SubQ: Squamous cell carcinoma, lymphoma, testicular carcinoma: 0.25-0.5 units/kg (10-20 units/m2) 1-2 times/week
CIV: 15 units/m2 over 24 hours daily for 4 days
Pleural sclerosing: Intrapleural: 60 units as a single instillation (some recommend limiting the dose in the elderly to 40 units/m2; usual maximum: 60 units). Dose may be repeated at intervals of several days if fluid continues to accumulate (mix in 50-100 mL of NS); may add lidocaine 100-200 mg to reduce local discomfort.
Dosing adjustment in renal impairment:
Clcr 10-50 mL/minute: Administer 75% of normal dose
Clcr <10 mL/minute: Administer 50% of normal dose
Dosage: Combination Regimens
Head and neck cancer: CABO
Lymphoma, Hodgkin's:
ABVD
BEACOPP
CAD/MOPP/ABV
MOPP/ABV Hybrid
MOPP/ABVD
Stanford V
Lymphoma, non-Hodgkin's:
CEPP(B)
COP-BLAM
MACOP-B
m-BACOD
Pro-MACE-CytaBOM
Melanoma: BOLD
Ovarian cancer:
BEP (Ovarian)
BEP (Ovarian, Testicular)
Testicular cancer:
BEP (Ovarian, Testicular)
BEP (Testicular)
PVB
VBP
Administration: I.M.
May cause pain at injection site.
Administration: I.V.
May be an irritant. I.V. doses should be administered slowly (manufacturer recommends giving over a period of 10 minutes).
Administration: Other
Intrapleural: 60 units in 50-100 mL NS; use of topical anesthetics or narcotic analgesia is usually not necessary
SubQ: May cause pain at injection site.
Administration: I.V. Detail
pH: 4-6 (reconstituted solution, varies depending on diluent)
Monitoring Parameters
Pulmonary function tests (total lung volume, forced vital capacity, carbon monoxide diffusion), renal function, liver function, chest x-ray, temperature initially; check body weight at regular intervals
Patient Education
Do not take any new medications during treatment unless approved by prescriber. This medication can only be administered by injection or infusion; report immediately any redness, burning, pain, or swelling at injection/infusion site. May cause loss of appetite, nausea, or vomiting (small, frequent meals, sucking lozenges, or chewing gum may help); mouth sores (frequent mouth care with soft swabs and mouth rinses may help); fever or chills (will usually resolve); redness, peeling, or increased color of skin; or loss of hair (reversible after cessation of therapy). Report any change in respiratory status; respiratory difficulty; wheezing; air hunger; increased secretions; difficulty expectorating secretions; confusion; unresolved fever or chills; sores in mouth; vaginal itching, burning, or discharge; sudden onset of dizziness; acute headache; or burning, stinging, redness, or swelling at injection site. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Consult prescriber for instruction on appropriate contraceptives. This drug may cause severe fetal defects. Breast-feeding is not recommended
Geriatric Considerations
Pulmonary toxicity has been reported more frequently in geriatric patients (>70 years of age).
Anesthesia and Critical Care Concerns/Other Considerations
The use of oxygen concentrations (>30%) in animals previously treated with bleomycin has been reported to promote pulmonary toxicity. Although this is still controversial, supplemental oxygen should be used judiciously in patients who have received bleomycin.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
May rarely produce myelosuppression; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess pulmonary and pregnancy status prior to beginning therapy. Assess other pharmacological or herbal products patient may be taking for potential interactions. Pulmonary status should be evaluated for fine rales prior to each treatment (may be the first symptom of pulmonary toxicity) and prescriber notified of any changes. Lymphoma patients should be closely monitored for 1 hour following test dose before remainder of dose is administered. Infusion or injection site must be monitored closely to avoid extravasation. Assess results of laboratory tests (pulmonary, renal, and hepatic function), therapeutic effectiveness, and adverse reactions regularly during therapy. Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Injection, powder for reconstitution, as sulfate: 15 units, 30 units
References
Aronoff GR, Berns JS, Brier ME, et al, "Drug Prescribing in Renal Failure: Dosing Guidelines for Adults," 4th ed. Philadelphia, PA: American College of Physicians; 1999, p. 73.
Lamey PJ and Lewis MAO, “Oral Medicine in Practice: White Patches,” Br Dent J, 1990, 168(4):147-52.
Lazo JS and Sebti SM, “Bleomycin,” Cancer Chemother Biol Response Modif, 1994, 15:44-50.
Lazo JS, Sebti SM, and Schellens JH, “Bleomycin,” Cancer Chemother Biol Response Modif, 1996, 16:39-47.
Mir LM, Tounekti O, and Orlowski S, “Bleomycin: Revival of an Old Drug,” Gen Pharmacol, 1996, 27(5):745-8.
International Brand Names
Lexi-Comp.com
Last full review/revision June 2006
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