Consumer medicine information

BLENAMAX

Bleomycin sulfate

BRAND INFORMATION

Brand name

Blenamax Powder for injection

Active ingredient

Bleomycin sulfate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using BLENAMAX.

What is in this leaflet

This leaflet answers some common questions about BLENAMAX®. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking BLENAMAX® against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What BLENAMAX is used for

BLENAMAX® is used to treat some types of cancers, and is also used to prevent or treat build-up of fluid around the lungs which can result from cancer. BLENAMAX® belongs to a group of medicines called antineoplastic or cytotoxic medicines. You may also hear of these being called chemotherapy medicines. BLENAMAX® is thought to work by stopping cancer cells from growing and multiplying. Your doctor may have prescribed BLENAMAX® for another reason. Ask your doctor if you have any questions about why BLENAMAX® has been prescribed for you.

BLENAMAX® may be used in combination with other medicines to treat cancer.

BLENAMAX® is not addictive.

This medicine is available only with a doctor's prescription.

BLENAMAX® is not recommended for use in children, as there is not enough information on its effects in children.

Before you use it

When you must not use it

Do not have BLENAMAX® if you have an allergy to bleomycin sulfate or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to BLENAMAX may include:

  • shortness of breath
  • wheezing
  • difficulty breathing or a tight feeling in your chest
  • swelling of the face, lips, tongue or other parts of the body
  • rash
  • itching
  • hives or flushed, red skin
  • dizziness or light headedness
  • back pain

Your doctor may give you a small test dose to see how you react to BLENAMAX®.

Do not have this medicine if you have previously had lung problems while receiving bleomycin.

If you are not sure whether you should start having BLENAMAX®, talk to your doctor or pharmacist.

Before you are given it

You must tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes

Tell your doctor if you have or have had any of the following health/medical conditions, especially the following:

  • liver problems
  • kidney problems
  • lung problems, including asthma

Tell your doctor if you smoke.

There is a greater chance of bleomycin affecting your lungs if you smoke.

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

Like most medicines used to treat cancer, BLENAMAX® is not recommended to be used during pregnancy. (If there is a need to consider it during your pregnancy, your doctor will discuss with you the benefits and risks of using it.)

Tell your doctor if you are breast-feeding or plan to breast-feed.

It is recommended that you do not breast-feed while taking BLENAMAX®, as it may pass into breast milk and therefore there is a possibility that the breast-fed baby may be affected.

If you have not told your doctor about any of the above, tell them before you start having BLENAMAX®.

Taking other medicines

Tell your doctor or pharmacist if you are having any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and BLENAMAX® may interfere with each other. These include:

  • phenytoin, a medicine used to threat epilepsy;
  • digoxin, a medicine used to treat heart failure.

These medicines may be affected by BLENAMAX®, or may affect how well it works. You may need different amounts of your medicine, or you may need to have different medicines. Your doctor or pharmacist will advise you. Your doctor and pharmacist may have more information on medicines to be careful with or avoid while having BLENAMAX®.

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight, kidney function and other chemotherapy medicines you are being given. BLENAMAX® may be given alone or in combination with other drugs.

BLENAMAX® is given as a course or 'cycle'. You may receive a small test dose to check that you are not allergic. If no reaction occurs within 4-6 hours, the rest of the course will be given. A course may consist of a dose once or twice weekly, or it may be a cycle of a daily dose for 7 consecutive days. Several courses of BLENAMAX® therapy may be needed depending on your response to treatment. Additional treatment may not be repeated until your blood cell numbers return to acceptable levels and any uncontrolled effects have been controlled.

Ask your doctor if you want to know more about the dose of BLENAMAX® you receive.

How to take it

How it is given

BLENAMAX® must only be given by a doctor, nurse or other trained person.

BLENAMAX® is given as an injection either:

  • under the skin
  • into a vein
  • into a muscle
  • into an artery
  • into the space around the lungs.

If you take too much (Overdose)

As BLENAMAX® is given to you under the supervision of your doctor, it is very unlikely that you will receive too much.

However, if you experience any side effects after being given BLENAMAX®, tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

You may need urgent medical attention.

Symptoms of a BLENAMAX® overdose include the side effects listed below in the 'Side Effects' section, but are usually of a more severe nature.

While you are using it

Things you must do

Be sure to keep all your doctor's appointments so your progress can be checked.

Your doctor may want to check your blood pressure and do some blood tests and other tests from time to time to check on your progress and detect any unwanted side effects.

In particular, your doctor will need to do checks on your lungs since BLENAMAX® is known to affect the way the lungs work in some people.

Keep follow up appointments with your doctor.

It is important to have your follow-up doses of BLENAMAX® at the appropriate times to get the best effects from your treatments.

Tell any other doctors, dentists, and pharmacists who are treating you that you are having BLENAMAX®.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are having BLENAMAX®.

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are having BLENAMAX® or have received BLENAMAX® in the last 12 months.

If you become pregnant while having this medicine, tell your doctor.

BLENAMAX® may cause birth defects if either the male or the female is receiving it at the time of conception or if it is used during pregnancy. You should use some form of birth control while you are receiving this medicine.

Things to be careful of

Be careful driving or operating machinery until you know how BLENAMAX® affects you.

As with some other medicines, BLENAMAX® may cause tiredness in some people. Make sure you know how you react to BLENAMAX® before you drive a car, operate machinery, or do anything else that could be dangerous if you are tired.

If this occurs do not drive.

If you drink alcohol, tiredness may be worse.

Side effects

During treatment with BLENAMAX®, you will require close medical supervision. It is important that you tell your doctor or nurse immediately if you have any problems, or if you do not feel well while you are having BLENAMAX®.

Like other medicines that treat cancer, BLENAMAX® may have unwanted side effects, some of which may be serious. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • feeling sick
  • vomiting
  • loss of appetite
  • weight loss
  • headache
  • tiredness
  • itching
  • hives
  • redness of the skin
  • discolouration of skin and nails
  • skin rash
  • irritation, pain swelling or colouring of the skin around the needle during injection
  • unusual hair loss or thinning

These are the more common side effects of BLENAMAX®.

Tell your doctor or nurse as soon as possible if you notice any of the following:

  • chills and fever
  • mouth ulcers
  • sore, red mouth
  • tiredness, headaches, being short of breath when exercising, dizziness and looking pale
  • lack of white blood cells * frequent infections, fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal
  • tingling or numbness in hands or feet; pins and needles
  • burning feeling when passing urine
  • blood in the urine
  • disorientation, behavioural changes
  • bleeding from eye

These may be serious side effects. You may need medical attention. If any of the following happen, tell your doctor or nurse immediately, or go to Accident and Emergency at your nearest hospital:

Sudden Life-threatening Allergic Reaction-

  • sudden signs of allergy such as rash, itching or hives on the skin
  • swelling of the face, tongue or other parts of the body
  • shortness of breath
  • wheezing or trouble breathing
  • swelling of the lungs causing coughing, difficulty breathing and wheezing

Heart Disease-

  • fatigue
  • chest pain
  • palpitations
  • altered heart beat
  • stroke.

These are very serious side effects. You may need urgent medical attention or hospitalisation. Other side effects not listed above may occur in some patients.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

The benefits and side effects of BLENAMAX® may take some time to occur.

Therefore even after you have finished your BLENAMAX® treatment you should tell your doctor immediately if you notice any of the side effects listed in this section.

After using it

If you are to have an operation at any time after you have received BLENAMAX®, tell your doctor that you have received this medicine.

Your doctor may need to take special measures to avoid the risk of lung problems.

Storage

BLENAMAX® must be stored at 2-8°C (Refrigerate. Do not freeze) and protected from light.

Product Description

What it looks like

BLENAMAX® is a cake of white powder in a glass vial. It must be dissolved in Water for Injection or 0.9% Sodium chloride solution before use. Each vial is used only once and any left over material is discarded.

Ingredients

Active ingredient:
bleomycin sulfate 15000 IU

Other ingredients:

  • sodium hydroxide
  • hydrochloric acid

BLENAMAX® does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

BRAND INFORMATION

Brand name

Blenamax Powder for injection

Active ingredient

Bleomycin sulfate

Schedule

S4

 

Name of the medicine

Bleomycin sulfate.

Excipients

Sodium hydroxide/ hydrochloric acid for pH adjustment.

Description

Bleomycin sulfate is the sulfate of a mixture of glycopeptides isolated from a strain of Streptomyces verticillus; the two principal components of the mixture are bleomycin A2 and B2. CAS: 9041-34-4.

Actions

Antineoplastic antibiotic.

Pharmacology

The exact mechanism of action of bleomycin is not known, but it is thought that the main action is to produce single and double strand breaks in DNA, causing inhibition of cell division and growth, and inhibition of DNA synthesis in the cells. Bleomycin is probably most effective against cells in the M and G2 (premitotic) phase of the cell cycle. It has not been shown to have an immunosuppressive effect in vitro and shows no significant inhibition of immune response in patients treated with the drug. The mechanism of action of bleomycin in the treatment of malignant pleural effusion is not completely known. The most likely mechanism is a local inflammatory effect resulting in fibrous adhesion as it resolves; however, a local cytotoxic effect cannot be entirely excluded. Bleomycin inactivating enzyme has been detected in both normal and malignant cells and is particularly prominent in the liver. The enzyme is not found in lung or skin, two normal tissues which are sensitive to bleomycin action.

Pharmacokinetics

Absorption.

Bleomycin is well absorbed in animals after intramuscular, intraperitoneal and subcutaneous administration. Intramuscular injection of 15,000 IU in humans resulted in a maximum serum concentration of 1 IU/mL 30 minutes after administration. Intravenous injection of 15,000 IU in humans resulted in a maximum serum concentration of 3.3 IU/mL.
The pharmacokinetics of bleomycin following intrapleural administration has only been studied in a small number of patients. The plasma levels resulting after intrapleural administration suggest a systemic absorption rate of approximately 45%. The effects of age and concurrent therapy on the pharmacokinetics after this route of administration have not been adequately studied.

Distribution.

In mice, high concentrations of bleomycin were found in the skin, lungs, kidneys, peritoneum, lymphatic system and susceptible tumour tissue if present. Tissue concentrations are particularly high in skin and lungs, while the concentration is very low in the brain and cerebrospinal fluid. In pregnant mice, bleomycin is recovered in high concentrations in the amniotic fluid and placenta, and to a lesser extent in the fetus.

Protein binding.

Equilibrium dialysis and gel permeation experiments indicate that less than 1% of the drug is protein bound after in vitro incubation with normal human serum.

Metabolism.

A considerable portion of each dose is not readily metabolised or inactivated. Liver, gastrointestinal tissues and, to a lesser extent, muscle, skin, lung, kidney and serum have demonstrated a capacity to degrade bleomycin.

Excretion.

The major route of excretion of bleomycin is the kidney, with 60 to 70% of an administered dose recovered in the urine as active bleomycin. Renal dysfunction can significantly prolong excretion. In patients with a creatinine clearance of > 35 mL/minute, the serum or plasma terminal elimination half-life of bleomycin is approximately 115 minutes. In patients with a creatinine clearance < 35 mL/minute, the plasma or serum terminal elimination half-life increases exponentially as the creatinine clearance decreases. An association has been reported between decreased renal function and enhanced bleomycin related toxicities. It is thought that the enhancement of toxicity is a result of reduced renal clearance of bleomycin, leading to prolonged elimination half-life and increased area under the plasma concentration versus time curve, when compared to patients with normal renal function. Dosage reductions of 40 to 75% have been recommended for patients with creatinine clearance values less than or equal to 40 mL/minute.

Indications

Palliative treatment and/or adjuvant treatment to surgery and/or radiation therapy in the management of the following neoplasms.
The primary indication is the treatment of squamous cell carcinoma of the skin, head and neck and oesophagus. Tumour response has also been obtained in a number of patients with squamous cell carcinoma of the penis, larynx and uterine cervix. Squamous cell carcinoma of the bronchus has shown infrequent response. Bleomycin is also indicated in the treatment of choriocarcinoma and embryonal cell carcinoma of the testis.
It has been used effectively in advanced Hodgkin's disease and in some cases of other lymphomas such as non-Hodgkin's lymphoma and in mycosis fungoides.
Bleomycin is bone marrow sparing and may therefore be of use when other cytotoxic agents are contraindicated.
It should be noted that treatment of patients with bleomycin after radiation therapy is less successful than treatment prior to radiation therapy. Bleomycin is effective as a sclerosing agent for the treatment of malignant pleural effusion. It should be given as a single instillation only, as studies have not assessed the efficacy or safety of multiple intrapleural dosing.

Contraindications

Known hypersensitivity to the drug.

Precautions

Bleomycin should be administered under the supervision of a qualified doctor 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. Patients receiving bleomycin must be observed carefully and frequently during and after therapy.

Pulmonary toxicity.

This is the most serious toxicity associated with bleomycin (see Adverse Reactions).
Patients undergoing treatment should have chest X-rays every one to two weeks, continuing until four weeks after the course is completed. If pulmonary changes are observed, treatment should be discontinued to determine whether the cause is drug related. Prompt treatment of pneumonitis should be instituted, with the use of antibiotics and steroids being considered. A repeat course of treatment is contraindicated in any patient who has shown signs of pneumonitis or decreased pulmonary function.

Anaesthesia.

Patients treated with bleomycin are at risk of developing the acute adult respiratory distress syndrome postoperatively 6 to 12 months after initial chemotherapy. In order to minimise the risk in patients undergoing surgery who have received bleomycin, the following preventive measures are recommended.
Use a low concentration of inspiratory oxygen (below 0.25) during surgery and the postoperative recovery period; and
avoid pulmonary interstitial oedema by carefully monitoring fluid replacement and restricting crystalloids in favour of colloids.

Lung cancer.

Bleomycin should be used with extreme caution in patients with lung cancer, as these patients show an increased incidence of pulmonary toxicity.

Cumulative dose.

Pulmonary toxicity is more common in patients receiving a total dose of more than 400,000 IU (400 units USP).

Renal or hepatic toxicity.

Renal or hepatic toxicity, commencing as a deterioration in renal or liver function tests, has been reported infrequently, but may occur at any time after initiation of therapy.

Idiosyncratic reactions.

Idiosyncratic reactions similar to anaphylaxis have been reported in lymphoma patients treated with bleomycin. Since these usually occur after the first or second dose, careful monitoring is essential after these doses.

Lymphoma patients.

All lymphoma patients should receive test doses of bleomycin before initiating full dose therapy, since there is a possibility of anaphylaxis (see Adverse Reactions and Dosage and Administration).

Compromised pulmonary function due to disease other than malignancy.

Bleomycin should be used with extreme caution as it is particularly prone to cause pulmonary toxicity.

Impaired renal function

Bleomycin should be used with extreme caution in patients with significant impairment of renal function (see Dosage and Administration).

Use in the elderly

Patients over 70 years of age should be closely observed for signs of pulmonary toxicity due to bleomycin therapy (see Adverse Reactions), as there is an apparent increased risk of this toxicity.

Carcinogenesis, mutagenesis, impairment of fertility

The carcinogenic potential of bleomycin in humans is unknown; however, as for other cytotoxic agents, the possibility of carcinogenic potential cannot be excluded. Bleomycin has been shown to be mutagenic in in vitro and in vivo test systems. It is teratogenic in rats and mice when administered during organogenesis. The effect on fertility has not been established.

Use in pregnancy.

(Category D)
Bleomycin is moderately teratogenic in animals. Administration to pregnant women is not recommended unless the expected benefit outweighs the potential risk to the fetus.

Use in lactation.

It is not known whether bleomycin is excreted in breast milk or whether it has a harmful effect on the newborn. Therefore it is not recommended for breastfeeding mothers unless the expected benefits outweigh any potential risks to the baby.

Interactions

Serum levels of digoxin may be reduced and its actions may be decreased. It is thought that drug induced alterations of the intestinal mucosa may be involved in the reduced gastrointestinal absorption.
Concentrations of phenytoin may be decreased due to decreased absorption or increased metabolism of phenytoin.
Human serum has been shown to intensify the growth inhibiting action of bleomycin on Ehrlich ascites tumour cells in suspension culture.

Adverse Effects

More common reactions.


Skin and mucous membranes.

Mucocutaneous toxicity (see below).

Gastrointestinal.

Nausea, vomiting, anorexia, weight loss.

General.

Fever, chills, headache, tiredness.

Less common reactions.


Respiratory.

Pulmonary toxicity (see below).

Allergic.

Anaphylaxis (see Idiosyncratic reactions, below).

Genitourinary.

Renal toxicity (commencing as a deterioration in renal function tests), haematuria, cystitis.

Hepatic.

Hepatic toxicity (commencing as a deterioration in liver function tests).

Neurological.

Central nervous system toxicity, disorientation, aggressive behaviour.

Haematological.

Thrombocytopenia, leucopenia, slight anaemia.

Ophthalmological.

Ocular haemorrhage.

Injection site reactions.

Pain at the tumour site, phlebitis, local reactions.

Vascular.

Raynaud's phenomenon; myocardial infarction, cerebrovascular accident, thrombotic microangiopathy (haemolytic uraemic syndrome), cerebrovascular arteritis (usually in combination with other antineoplastic agents).

Other.

Acute chest pain syndrome (suggestive of pleuropericarditis).

Pulmonary toxicity.

The most serious toxicity of bleomycin is a subacute or chronic pneumonitis that progresses to interstitial fibrosis and may be fatal. This occurs in approximately 10% of treated patients, about 1% of whom have died of pulmonary fibrosis. Pulmonary toxicity is both age and dose related, being more common in patients over 70 years of age and in those who have received a cumulative dose of over 400,000 IU (400 units USP). However, this toxicity is unpredictable and has been seen occasionally in young patients receiving low doses. Also, pulmonary toxicities may occur at lower doses when bleomycin is used in combination with other antineoplastic agents. This toxicity is frequently seen in those with underlying lung disease such as emphysema and in those previously treated with pulmonary or mediastinal irradiation, and is also seen more commonly in smokers. The identification of patients with pulmonary toxicity due to bleomycin has been extremely difficult. The clinical symptoms and X-ray findings of bleomycin pulmonary toxicity are not easily distinguished from other syndromes commonly observed in cancer patients, including progressive metastatic tumour (especially lymphangitic tumour), infectious processes such as Pneumocystis carinii or cytomegalovirus, or radiation injury. The first symptoms to appear are dyspnoea, with cough and low grade fever, occurring four to ten weeks after initiation of therapy. The earliest sign is fine rales. The microscopic tissue changes due to bleomycin toxicity are frequently present as bronchiolar squamous metaplasia, reactive macrophages, atypical alveolar epithelial cells, fibrinous oedema 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 and are similar to the changes produced in radiation pneumonitis, pneumocystic pneumonitis and at times reaction to long standing malignant pulmonary disease. To monitor the onset of pulmonary toxicity, X-rays of the chest should be taken every one to two weeks. 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 (DLCO) during treatment with bleomycin may be an indicator of subclinical pulmonary toxicity. It is recommended that the DLCO be monitored monthly if it is to be employed to detect pulmonary toxicity, and the drug should be discontinued when the DLCO falls below 30 to 35% of the pretreatment value. There is a potential for an increased risk of pulmonary toxicity when oxygen is given in any clinical situation.
Pneumonitis due to bleomycin should be treated with corticosteroids in an effort to prevent progression to pulmonary fibrosis.
Bacterial pneumonitis should receive appropriate antibiotic therapy. Bleomycin hypersensitivity pneumonitis has been reported in three patients who developed radiological and function changes similar to the usual bleomycin interstitial pneumonitis. However, lung biopsies showed a pattern of hypersensitivity reaction, which responded promptly to prednisone treatment. Because of bleomycin's sensitisation of lung tissue, patients who have received bleomycin are at a greater risk of developing pulmonary toxicity when oxygen is given at surgery (see Precautions, Anaesthesia).

Idiosyncratic reactions.

Hypersensitivity reactions consisting of hypotension, fever, chills, mental confusion, wheezing and death in some instances have occurred in approximately 1% of patients receiving bleomycin, mainly in lymphoma patients (5%). This reaction may be immediate or delayed for several hours, and usually occurs after the first or second dose. Careful monitoring after these doses is essential and test doses are recommended (see Dosage and Administration). Treatment of anaphylactoid reactions is supportive and symptomatic and may include volume expansion, vasopressor therapy, antihistamines and corticosteroids.

Mucocutaneous reactions.

Mucocutaneous toxicity is the most frequent adverse effect of bleomycin and is seen in approximately 50% of patients treated. The incidence and severity are increased when bleomycin is given in combination with radiotherapy to the head and neck. In 0.2% of patients it was necessary to discontinue treatment because of this toxicity.
This toxicity is usually evident within one to three weeks following initiation of therapy and appears to be reversible and dose related, usually occurring after 150,000 to 200,000 IU (150 to 200 units USP) of bleomycin have been administered and, in general, is related to total cumulative dose. The effects disappear slowly once the drug is withdrawn. The onset may be accompanied by hypoaesthesia which may progress to hyperaesthesia; paraesthesia has also been reported. Skin toxicity may be initially manifested as urticaria or erythematous swelling; lesions may then become tender and pruritic. Hyperpigmentation is frequently reported, occurring particularly in those areas subject to friction or pressure and in skin folds, nail cuticles, scars and intramuscular injection sites. Patchy hyperkeratosis has also been frequently reported. Diffuse alopecia of varying degrees may occur in patients receiving bleomycin therapy. Other reported skin reactions include ichthyosis, rash, striae, vesiculation, peeling and bleeding. Mucosal lesions, including stomatitis and ulcerations of the tongue and lips may also occur. When bleomycin is administered intra-arterially, dermal lesions are most common in the region supplied by the artery used.

Dosage and Administration

Bleomycin may be given by the intramuscular (IM), intravenous (IV), subcutaneous (SC) or intra-arterial or intrapleural routes. The dose regimen used depends on the response of the patient.

Note.

Because of the possibility of an anaphylactoid reaction, lymphoma patients should receive test doses of between 1,000 and 5,000 IU (1 to 5 units USP), for the first two treatments. If no acute allergic reaction occurs within four to six hours, the balance of the dose may be given. Thereafter the regular dosage schedule may be followed, if no reaction occurs.

Adults.

Initial treatment.

Intramuscular, intravenous or subcutaneous administration.

10,000 to 20,000 IU (10 to 20 units USP)/m2 of body surface area may be given weekly or twice weekly. Alternatively, give 15,000 IU (15 units USP) daily for seven days followed by three weeks off treatment and repeat twice so that a total dose of approximately 300,000 IU (300 units USP) is administered. Improvement of lymphomas and testicular tumours is prompt, i.e. within two weeks while response by squamous cell cancers may take as long as three weeks. A therapeutic response should be observed as the total dose approaches 150,000 IU (150 units USP), and if this is not seen, consideration should be given to other therapy. Total doses of over 300,000 IU (300 units USP) should be given with great caution.

Intra-arterial administration.

Intra-arterial infusion/ perfusion is employed when increased drug concentrations at the cancer site are desired. The suggested dosage schedule is 30,000 to 60,000 IU (30 to 60 units USP) once or twice a week until the total recommended dose of 300,000 IU (300 units USP) is reached.

Repeat treatment.

In patients for whom a course of bleomycin treatment provides an initial but incomplete response, a repeat course is suggested.
Patients who show superficial improvement after one course, e.g. in cases of squamous cell carcinoma, may benefit from a second course of treatment to prevent recurrence.
A repeat course may be commenced after a minimum of three to four weeks following completion of the first course, providing no signs of pulmonary toxicity have been observed. A total dose of 150,000 IU (150 units USP) for repeat treatment is recommended, using a schedule as described above.

Paediatric dose.

No information is available.

Geriatric dose.

Adult dose should be used with caution, particularly in patients over 70 years (see Adverse Reactions, Pulmonary toxicity).

In impaired liver function.

Use adult dose with caution.

In impaired renal function.

As bleomycin is mostly excreted unchanged and as there is a high correlation between renal bleomycin clearance and creatinine clearance, impairment of renal function may require a reduction in dosage and careful monitoring for toxicity.
Dosage reductions of 40 to 75% have been recommended for patients with creatinine clearance values of less than or equal to 40 mL/minute.

Directions for reconstitution.

For IM or SC injection, the contents of the vial should be dissolved in 1 to 5 mL of sterile water for injection or sodium chloride intravenous infusion 0.9%.
For IV or intra-arterial injection, the contents of the vial should be dissolved in 5 to 10 mL of diluent and administered slowly over a period of ten minutes.
Suitable diluents are water for injections, sodium chloride 0.9% solution, and sodium chloride 0.9% and dextrose 5% solution.
Reconstituted solutions prepared using the recommended diluents remain stable for periods of at least 24 hours at 25°C. However, in order to reduce microbiological contamination, reconstituted solutions should be used as soon as practicable after preparation. If storage of the reconstituted solution is necessary, store at 2 to 8°C for no more than 24 hours. Any unused portions must be discarded in compliance with acceptable procedures for the disposal of anticancer drugs.

Malignant pleural effusion.

60,000 IU (60 units USP) administered as a single dose bolus intrapleural injection is the most commonly used dose, with a low reported rate of toxicity. The optimal dose of intrapleural bleomycin in the treatment of malignant pleural effusion has not been established; but it has been reported to be effective using a dose of 30,000 IU (30 units USP). The efficacy of lower doses has not been adequately studied.
For intrapleural administration, 60,000 IU (60 units USP) should be dissolved in 50 to 100 mL sodium chloride injection 0.9% and administered through a thoracostomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The thoracostomy tube is then clamped. The patient should be 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 re-established. The intrapleural injection of topical anaesthetics or systemic narcotic analgesia is generally not required.

Special warnings.

Procedures for proper handling and disposal of anticancer drugs should be used.
Bleomycin is incompatible with amino acids, aminophylline, ascorbic acid, dexamethasone, frusemide, hyoscine, butylbromide and riboflavine.
Blenamax contains no preservative.
Each vial should be used once only and any residue discarded.

Overdosage

There has been no reported case of overdosage and there is no specific antidote.
The acute reaction would probably include hypotension, fever, rapid pulse and general symptoms of shock. Treatment would be symptomatic. In the event of respiratory complications, treatment with a corticosteroid may be beneficial and the administration of a broad spectrum antibiotic is advisable. Bleomycin is probably not dialysable.

Presentation

Lyophilised powder for reconstitution, 15,000 IU: 1's*, 10's (vial).
*Not currently marketed in Australia.

Storage

Store at 2-8°C. (Refrigerate. Do not freeze). Protect from light.

Shelf life.

3 years.

Poison Schedule

S4.