BLENOXANE® (bleomycin sulfate for injection, USP) is a mixture of cytotoxic glycopeptide antibiotics isolated from a strain of Streptomyces verticillus. It is freely soluble in water.

Note: A unit of bleomycin is equal to the formerly used milligram activity. The term milligram activity is a misnomer and was changed to units to be more precise.

BLENOXANE 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 BLENOXANE 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.

BLENOXANE has also been shown to be useful in the management of:

Malignant Pleural Effusion

BLENOXANE is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions.

Because of the possibility of an anaphylactoid reaction, lymphoma patients should be treated with 2 units or less for the first two 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/m²) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly.

Hodgkin's Disease—0.25 to 0.50 units/kg (10 to 20 units/m²) 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 BLENOXANE 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 BLENOXANE (bleomycin sulfate for injection, USP) 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/1.73m², weight in kg, age in years, and Scr in mg/dL.

Administration

BLENOXANE may be given by the intramuscular, intravenous, subcutaneous, or intrapleural routes.

To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing BLENOXANE for injection. This includes all handling activities in clinical settings, pharmacies, storerooms, and home healthcare settings, including during unpacking and inspection, transport within a facility, and dose preparation and administration.

Intramuscular or Subcutaneous

The BLENOXANE 15 units vial should be reconstituted with 1 to 5 mL of Sterile Water for Injection, USP, Sodium Chloride for Injection, 0.9%, USP, or Sterile Bacteriostatic Water for Injection, USP. The BLENOXANE 30 units vial should be reconstituted with 2 to 10 mL of the above diluents.

Intravenous

The contents of the 15 units or 30 units vial should be dissolved in 5 mL or 10 mL, respectively, of Sodium Chloride for Injection, 0.9%, USP, and administered slowly over a period of 10 minutes.

Intrapleural

Sixty units of BLENOXANE are dissolved in 50–100 mL Sodium Chloride for Injection, 0.9%, USP, and administered through a thoracostomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The literature suggests that successful pleurodesis is, in part, dependent upon complete drainage of the pleural fluid and reestablishment of negative intrapleural pressure prior to instillation of a sclerosing agent. Therefore, the amount of drainage from the chest tube should be as minimal as possible prior to instillation of BLENOXANE. Although there is no conclusive evidence to support this contention, it is generally accepted that chest tube drainage should be less than 100 mL in a 24-hour period prior to sclerosis. However, BLENOXANE instillation may be appropriate when drainage is between 100–300 mL under clinical conditions that necessitate sclerosis therapy. The thoracostomy tube is clamped after BLENOXANE instillation. The patient is moved from the supine to the left and right lateral positions several times during the next four hours. The clamp is then removed and suction reestablished. The amount of time the chest tube remains in place following sclerosis is dictated by the clinical situation.

The intrapleural injection of topical anesthetics or systemic narcotic analgesia is generally not required.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

BLENOXANE® (bleomycin sulfate for injection, USP) is available as follows:

NDC 0015-3010-20, 15 units per vial as bleomycin sulfate for injection, USP.
NDC 0015-3063-01, 30 units per vial as bleomycin sulfate for injection, USP.

Stability

The sterile powder is stable under refrigeration 2° C (36° F) to 8° C (46° F) and should not be used after the expiration date is reached.

BLENOXANE should not be reconstituted or diluted with D₅W or other dextrose containing diluents. When reconstituted in D5W and analyzed by HPLC, BLENOXANE demonstrates a loss of A₂ and B₂ potency that does not occur when BLENOXANE is reconstituted in Sodium Chloride for Injection, 0.9%, USP.

BLENOXANE is stable for 24 hours at room temperature in Sodium Chloride.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.^1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

REFERENCES

1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 1999:32-41.

2. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety, Clinical Center Pharmacy Department and Cancer Nursing Services, National Institutes of Health; 1992. US Dept of Health and Human Services, Public Health Service Publication NIH 92-2621.

3. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1592.

4. National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.

5. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust. 1983;1:426-428.

6. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from The Mount Sinai Medical Center. CA Cancer J Clin. 1983;33:258-263.

7. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049.

8. Controlling occupational exposure to hazardous drugs. (OSHA Work-Practice Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.

Manufactured by: Nippon Kayaku Co., Ltd. Tokyo, Japan. Distributed by: Bristol-Myers Squibb Company, Princeton, NJ 08543 USA. Revised August 2006. FDA Rev date: 6/30/2004

Pulmonary

This is potentially the most serious side effect, 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 occasionally 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 BLENOXANE (bleomycin sulfate for injection, USP) has been extremely difficult. The earliest symptom associated with BLENOXANE pulmonary toxicity is dyspnea. The earliest sign is fine rales.

Radiographically, BLENOXANE-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 BLENOXANE toxicity include bronchiolar squamous metaplasia, reactive macrophages, atypical alveolar epithelial cells, fibrinous edema, and interstitial fibrosis. The acute stage may involve capillary changes and subsequent fibrinous exudation into alveoli producing a change similar to hyaline membrane formation and progressing to a diffuse interstitial fibrosis resembling the Hamman-Rich syndrome. These microscopic findings are nonspecific; eg, similar changes are seen in radiation pneumonitis and pneumocystic pneumonitis.

To monitor the onset of pulmonary toxicity, roentgenograms of the chest should be taken every 1 to 2 weeks (see WARNINGS). If pulmonary changes are noted, treatment should be discontinued until it can be determined if they are drug related. Recent studies have suggested that sequential measurement of the pulmonary diffusion capacity for carbon monoxide (DL_CO) during treatment with BLENOXANE may be an indicator of subclinical pulmonary toxicity. It is recommended that the DL_CO be monitored monthly if it is to be employed to detect pulmonary toxicities, and thus the drug should be discontinued when the DL_CO falls below 30% to 35% of the pretreatment value.

Because of bleomycin's sensitization of lung tissue, patients who have received bleomycin are at greater risk of developing pulmonary toxicity when oxygen is administered in surgery. While long exposure to very high oxygen concentrations is a known cause of lung damage, after bleomycin administration, lung damage can occur at lower concentrations that are usually considered safe. Suggested preventive measures are:

1. Maintain FIO₂ at concentrations approximating that of room air (25%) during surgery and the postoperative period.
2. Monitor carefully fluid replacement, focusing more on colloid administration rather than crystalloid.

Sudden onset of an acute chest pain syndrome suggestive of pleuropericarditis has been rarely reported during BLENOXANE infusions. Although each patient must be individually evaluated, further courses of BLENOXANE do not appear to be contraindicated.

Pulmonary adverse events which may be related to the intrapleural administration of BLENOXANE have been reported only rarely.

Idiosyncratic Reactions

In approximately 1% of the lymphoma patients treated with BLENOXANE (bleomycin sulfate for injection, USP), an idiosyncratic reaction, similar to anaphylaxis clinically, has been reported. The reaction may be immediate or delayed for several hours, and usually occurs after the first or second dose (see WARNINGS). It consists of hypotension, mental confusion, fever, chills, and wheezing. Treatment is symptomatic including volume expansion, pressor agents, antihistamines, and corticosteroids.

Integument and Mucous Membranes

These are the most frequent side effects, being reported in approximately 50% of treated patients. These consist of erythema, rash, striae, vesiculation, hyperpigmentation, and tenderness of the skin. Hyperkeratosis, nail changes, alopecia, pruritus, and stomatitis have also been reported. It was necessary to discontinue BLENOXANE therapy in 2% of treated patients because of these toxicities.

Scleroderma-like skin changes have also been reported as part of postmarketing surveillance.

Skin toxicity is a relatively late manifestation usually developing in the second and third week of treatment after 150 to 200 units of BLENOXANE have been administered and appears to be related to the cumulative dose.

Intrapleural administration of BLENOXANE has occasionally been associated with local pain. Hypotension possibly requiring symptomatic treatment has been reported infrequently. Death has been very rarely reported in association with BLENOXANE pleurodesis in these very seriously ill patients.

Other

Vascular toxicities coincident with the use of BLENOXANE in combination with other antineoplastic agents have been reported rarely. The events are clinically heterogeneous and may include myocardial infarction, cerebrovascular accident, thrombotic microangiopathy (HUS), or cerebral arteritis. Various mechanisms have been proposed for these vascular complications. There are also reports of Raynaud's phenomenon occurring in patients treated with BLENOXANE in combination with vinblastine with or without cisplatin or, in a few cases, with BLENOXANE as a single agent. It is currently unknown if the cause of Raynaud's phenomenon in these cases is the disease, underlying vascular compromise, BLENOXANE, vinblastine, hypomagnesemia, or a combination of any of these factors.

Fever, chills, and vomiting were frequently reported side effects. Anorexia and weight loss are common and may persist long after termination of this medication. Pain at tumor site, phlebitis, and other local reactions were reported infrequently.

Malaise was also reported as part of postmarketing surveillance.

No information provided.

Patients receiving BLENOXANE 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 BLENOXANE 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 BLENOXANE. 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 infrequently. These toxicities may occur, however, at any time after initiation of therapy.

Usage in Pregnancy

Pregnancy Category D

BLENOXANE can cause fetal harm when administered to a pregnant woman. It has been shown to be teratogenic in rats. Administration of intraperitoneal doses of 1.5 mg/kg/day to rats (about 1.6 times the recommended human dose on a unit/m² basis) on days 6–15 of gestation caused skeletal malformations, shortened innominate artery and hydroureter. BLENOXANE is abortifacient but not teratogenic in rabbits at IV doses of 1.2 mg/kg/day (about 2.4 times the recommended human dose on a unit/m² basis) given on gestation days 6–18.

There have been no studies in pregnant women. If BLENOXANE is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with BLENOXANE.

General

Patients with creatinine clearance values of less than 50 mL/min should be treated with caution and their renal function should be carefully monitored during the administration of bleomycin. Lower doses of BLENOXANE may be required in these patients than those with normal renal function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of BLENOXANE in humans is unknown. A study in F344-type male rats demonstrated an increased incidence of nodular hyperplasia after induced lung carcinogenesis by nitrosamines, followed by treatment with bleomycin. In another study where the drug was administered to rats by subcutaneous injection at 0.35 mg/kg weekly (3.82 units/m² weekly or about 30% at the recommended human dose), necropsy findings included dose-related injection site fibrosarcomas as well as various renal tumors. Bleomycin has been shown to be mutagenic both in vitro and in vivo. The effects of bleomycin on fertility have not been studied.

Pregnancy

Pregnancy Category D

See WARNINGS.

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 BLENOXANE therapy.

Pediatric Use

Safety and effectiveness of BLENOXANE in pediatric patients have not been established.

Geriatric Use

In clinical trials, pulmonary toxicity was more common in patients older than 70 years than in younger patients (see BOX WARNING, WARNINGS, and ADVERSE REACTIONS: Pulmonary). Other reported clinical experience has not identified other differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Bleomycin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

No information provided.

BLENOXANE is contraindicated in patients who have demonstrated a hypersensitive or an idiosyncratic reaction to it.

Mechanism of Action

Although the exact mechanism of action of BLENOXANE 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, BLENOXANE acts as a sclerosing agent.

Pharmacokinetics

Absorption

Bleomycin is rapidly absorbed following either intramuscular (IM), subcutaneous (SC), intraperitoneal (IP) or intrapleural (IPL) administration reaching peak plasma concentrations in 30 to 60 minutes. Systemic bioavailability of bleomycin is 100% and 70% following IM and SC administrations, respectively, and 45% following both IP and IPL administrations, compared to intravenous and bolus administration.

Following IM doses of 1 to 10 units/m², both peak plasma concentration and AUC increased in proportion with the increase of dose.

Following IV bolus administration of 30 units of BLENOXANE to one patient with a primary germ cell tumor of the brain, a peak CSF level was 40% of the simultaneously-obtained plasma level and was attained in two hours after drug administration. The area under the bleomycin CSF concentration x time curve was 25% of the area of the bleomycin plasma concentration x time curve.

Distribution

Bleomycin is widely distributed throughout the body with a mean volume of distribution of 17.5 L/m² in patients following a 15 units/m² IV bolus dose. Protein binding of bleomycin has not been studied.

Metabolism

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 elimination 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 IV dose is excreted in urine within 24 hours. In patients with normal renal function, plasma concentrations of bleomycin decline biexponentially with a mean terminal half-life of 2 hours following IV bolus administration. Total body clearance and renal clearance averaged 51 mL/min/m² and 23 mL/min/m², respectively.

Following intrapleural administration to patients with normal renal function, a lower percentage of drug (40%) is recovered in the urine, as compared to that found in the urine after IV administration.

Special Populations

Age, Gender, and Race

The effects of age, gender, and race on the pharmacokinetics of BLENOXANE have not been evaluated.

Pediatric

Children of less than 3 years of age have higher total body clearance than in adults, 71 mL/min/m² versus 51 mL/min/m², respectively, following IV bolus administration. Children of more than 8 years of age have comparable clearance as in adults.

In children with normal renal function, plasma concentrations of bleomycin decline biexponentially as in adults. The volume of distribution and terminal half-life of bleomycin in children appears comparable to that in adults.

Renal Insufficiency

Renal insufficiency markedly alters bleomycin elimination. The terminal elimination half-life increases exponentially as the creatinine clearance decreases. Dosing reductions were proposed for patients with creatinine clearance values of <50 mL/min (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Hepatic Insufficiency

The effect of hepatic insufficiency on the pharmacokinetics of BLENOXANE has not been evaluated.

Drug Interactions

Drugs that Can Affect Renal Clearance

Because bleomycin is eliminated predominantly through renal excretion, the administration of nephrotoxic drugs with bleomycin may affect its renal clearance. Specifically, in one report of 2 children receiving concomitant cisplatin with bleomycin, total body clearance of bleomycin decreased from 39 to 18 mL/min/m² as the cumulative dose of cisplatin exceeded 300 mg/m². Terminal half-life of bleomycin also increased from 4.4 to 6.0 hours. Fatal bleomycin pulmonary toxicity has been reported in a patient with unrecognized cisplatin-induced oliguric renal failure.

Clinical Studies

Malignant Pleural Effusion

The safety and efficacy of BLENOXANE 60 units and tetracycline (1 g) as treatment for malignant pleural effusion were evaluated in a multicenter, randomized trial. Patients were required to have cytologically positive pleural effusion, good performance status (0,1,2), lung re-expansion following tube thoracostomy with drainage rates of 100 mL/24 hours or less, no prior intrapleural therapy, no prior systemic BLENOXANE therapy, no chest irradiation, and no recent change in systemic therapy. Overall survival did not differ between the BLENOXANE (n=44) and tetracycline treatment (n=41) groups. Of patients evaluated within 30 days of instillation, the recurrence rate was 36% (10/28) with BLENOXANE and 67% (18/27) with tetracycline (p=0.023). Toxicity was similar between groups.

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BLEOMYCIN - INJECTION

(blee-oh-MY-sin)

COMMON BRAND NAME(S): Blenoxane

WARNING: Infrequently, bleomycin can cause a serious, allergic-like reaction. It is most common in lymphoma patients. Before your main treatment with this drug begins, your doctor may direct you to receive a smaller test dose to check for signs of this serious reaction. Tell your doctor immediately if any of the following serious side effects occur: dizziness/fainting, confusion, fever, chills, trouble breathing.

Severe (sometimes fatal) lung problems (lung scarring) have infrequently occurred in patients using this drug. This reaction is more likely in patients older than 70 years. The risk of this reaction increases as you receive more doses of this drug. This problem may occur anytime during treatment. Tell your doctor immediately if you experience any of these serious side effects: cough, fever, chills, chest pain, or difficult/painful breathing.

USES: Bleomycin is used to treat cancer. It works by slowing or stopping the growth of cancer cells.

This medication may also be used to control the build-up of fluid around the lungs (pleural effusion) caused by tumors that have spread to the lungs. For this condition, bleomycin is placed in the space around the lungs through a chest tube.

HOW TO USE: Follow all instructions for proper mixing and dilution with the correct IV fluids. Do not mix bleomycin in solutions that contain dextrose. Before using, check this medication visually for particles. If particles are present, do not use the liquid.

This medication is given by injection into a vein, into a muscle, or under the skin by a health care professional usually once or twice a week or as directed by your doctor. When giving this medication into a vein, inject it slowly over 10 minutes. Tell your health care professional immediately if you experience any chest pain. The medication may need to be stopped or injected more slowly.

The dosage is based on your medical condition, body size, and response to treatment.

If you are receiving this medication through a chest tube into the space around the lungs, the solution is usually left in place for 4 hours and then drained out through the chest tube. Your doctor may direct you to change positions during the 4 hours to make sure the solution treats all parts of your lungs.

Learn how to handle, use, and discard chemotherapy and medical supplies safely. Wash your hands carefully after handling this drug. Consult your pharmacist.

SIDE EFFECTS: See also Warning section.

Pain/redness at the injection site, fever, chills, vomiting, loss of appetite, weight loss, darkening of the skin, or changes in fingernails/toenails may occur. Changes in diet such as eating several small meals or limiting activity may help lessen some of these effects. In some cases, drug treatment may be necessary to prevent or relieve nausea and vomiting. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Many people using this medication have serious side effects. However, your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.

Painful sores on the lips, mouth, and throat may occur. To decrease the risk, limit hot foods and drinks, brush your teeth carefully, avoid using mouthwash that contains alcohol, and rinse your mouth frequently with cool water.

Bleomycin can commonly cause skin reactions (e.g., redness, itching, blisters, rash, swelling), usually in the second or third week of treatment. These reactions are not always serious. However, you may not be able to tell them apart from signs of a severe reaction. Therefore, tell your doctor immediately if you develop any skin reaction.

Tell your doctor immediately if any of these unlikely but serious side effects occur: dizziness/fainting, fast/pounding heartbeat, numbness/tingling, feeling of coldness in hands/feet, pale/bluish skin.

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding, coughing up blood, vomit that looks bloody or like coffee grounds, signs of infection (e.g., persistent sore throat), change in the amount of urine, mental/mood changes (e.g., confusion, aggression), persistent nausea, stomach/abdominal pain, pink/dark urine, yellowing eyes/skin.

Seek immediate medical attention if any of these rare but very serious side effects occur: weakness on one side of the body, vision changes, slurred speech, chest pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: confusion, rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using bleomycin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially: immune system problems (e.g., chemotherapy, bone marrow problems), kidney disease, liver disease, lung problems.

This medication may make your lungs more sensitive to oxygen treatment. Therefore, tell your doctor or dentist that you have used this medication before having surgery or any treatment where oxygen may be used.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at greater risk for side effects (e.g., lung problems) while using this drug.

This medication is not recommended for use during pregnancy. It may harm the unborn baby. Consult your doctor for more details. If you become pregnant or think you may be pregnant, tell your doctor immediately.

It is not known whether this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: digoxin, drugs that may harm the kidneys (e.g., aminoglycosides such as gentamicin, cisplatin), phenytoin.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., chest X-rays, complete blood counts, kidney tests, liver tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor to establish a new dosing schedule. Do not double the dose to catch up.

STORAGE: Store in the refrigerator between 36-46 degrees F (2-8 degrees C). Mixed solutions can be stored at cool room temperature for up to 24 hours.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.