Bleomycin

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• fever or chills;
• sudden chest pain or discomfort, wheezing, dry cough or hack;
• shortness of breath;
• confusion, feeling weak or tired, loss of appetite, rapid weight loss;
• a light-headed feeling, feeling like you might pass out;
• white patches or sores inside your mouth or on your lips;
• severe redness, itching, rash, blistering, or tenderness of your skin; or
• unusual hardening or thickening of your skin.

Common side effects may include:

• dark streaks or discoloring on your skin;
• fingernail or toenail changes;
• temporary hair loss;
• mild itching;
• vomiting;
• pain near your tumor; or
• redness, warmth, itching, or swelling around the IV needle.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• cisplatin
• drugs that can decrease kidney function such as
  • acetaminophen (Tylenol)
  • aspirin
  • NSAIDs such as ibuprofen and naproxen
  • acyclovir
  • aminoglycoside medications
  • certain antibiotics
  • ACEIs such as lisinopril or quinapril
  • statins such as rosuvastatin and simvastatin
  • water pills (diuretic medications)

This is not a complete list of bleomycin drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if bleomycin crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using bleomycin.

• It is used to treat cancer.
• It is used to stop fluid buildup in the lung cavity.

Use bleomycin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot.
• It is given into the lung cavity.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Change in skin or finger nails.
• Change in color of skin.
• Mouth irritation or mouth sores.
• Weight loss.
• Not hungry.
• Hair loss.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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 0.5 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly.

Hodgkin’s Disease– 0.25 to 0.5 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 Bleomycin for Injection, USP 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, 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 x (140 – Age)]/(72 x Scr)

Females CrCL = 0.85 x [weight x (140 – Age)]/(72 x Scr)

Where CrCL in mL/min/1.73 m2, weight in kg, age in years, and Scr in mg/dL.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Generic: 15 units (1 ea); 30 units (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 15 units (1 ea); 30 units (1 ea)

Germ cell tumors, malignant

Data from a limited number of patients studied suggest that bleomycin (in combination with cisplatin and etoposide) may be beneficial for the treatment of ovarian germ cell tumors when used after tumor removal and thorough surgical staging [Williams 1994]. Data from a clinical trial in children and adolescents with high-risk malignant germ cell tumors suggest that bleomycin (in combination with cisplatin and etoposide) may be beneficial for the treatment of advanced testicular or ovarian germ cell tumors [Cushing 2004]. Additional data may be necessary to further define the role of bleomycin in this condition.

Hodgkin lymphoma (pediatrics)

Data from multiple studies support the use of bleomycin as part of various combination regimens for the treatment of Hodgkin lymphoma in pediatric patients [Dharmarajan 2015], [Friedman 2014], [Gordon 2013], [Horning 2000], [Horning 2002], [Hutchinson 1998], [Kelley 2002], [Schwartz 2009].

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, adjustment for hepatic impairment is not necessary (King 2001).

Pulmonary toxicity: Discontinue until determined not to be drug-related.

Pulmonary diffusion capacity for carbon monoxide (DLCO) <30% to 35% of baseline: Discontinue treatment.

Pulmonary diffusing capacity for carbon monoxide corrected for hemoglobin content [DLCOc] decrease of more than 25% during therapy (compared with baseline): Consider discontinuing bleomycin to avoid further pulmonary toxicity (Lauritsen 2016).

Note: During shortages within the US, temporary importation of international products may be allowed by the FDA. Refer to specific product labeling for reconstitution and preparation information.

For IV use, reconstitute 15-unit vial with 5 mL with NS and the 30-unit vial with 10 mL NS; for IM or SubQ use, reconstitute 15-unit vial with 1 to 5 mL of SWFI, BWFI, or NS and the 30-unit vial with 2 to 10 mL of SWFI, BWFI, or NS. For intrapleural use, mix in 50 to 100 mL of NS.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience change in skin or nails, weight loss, lack of appetite, hair loss, or loss of strength and energy. Have patient report immediately to prescriber signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), chills, confusion, severe dizziness, passing out, angina, severe mouth irritation, severe skin irritation, or injection site edema or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.