Bleomycin

CLINICAL USE

Antineoplastic agent

DOSE IN NORMAL RENAL FUNCTION

Squamous cell carcinoma and testicular teratoma:

range 45–60 × 10 3 IU per week IM/IV (total cumulative dose up to 500 × 103 IU)

OR, continuous IV infusion 15 × 10 3 IU/24 hours for up to 10 days

OR, 30 × 10 3 IU/24 hours for up to 5 days

Malignant lymphomas:15–30 × 10 3 IU/week IM to total dose of 225 × 103 IU Lower doses required in combination chemotherapy

Malignant effusions:60 × 10 3 IU in 100 mL sodium chloride 0.9% intrapleurally (total cumulative dose of 500 × 103 IU)

PHARMACOKINETICS

Molecular weight :Approximately 1500

%Protein binding :<1

%Excreted unchanged in urine : 60–70

Volume of distribution (L/kg) :0.3

half-life – normal/ESRD (hrs) :4 (bolus), 9 (continuous infusion)/20

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : 75% of normal dose (100% for malignant effusions)

<10 : 50% of normal dose (100% for malignant effusions)

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in GFR <10 mL/min

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unknown dialysability. Dose as in GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosis

Cytotoxics: increased pulmonary toxicity with cisplatin; in combination with vinca alkaloids can lead to Raynaud’s syndrome and peripheral ischaemia

ADMINISTRATION

Reconstition

IM: dissolve required dose in up to 5 mL sodium chloride 0.9% (or 1% solution of lidocaine if pain on injection)

IV: dissolve dose in 5–200 mL sodium chloride 0.9%

Intracavitary: 60 × 10 3 IU in 100 mL sodium chloride 0.9%

Locally: dissolve in sodium chloride 0.9% to make a 1–3 ×103 IU/mL solution

Route

IM, IV, also intra-arterially, intrapleurally, intraperitoneally, locally into tumour

Rate of Administration

Give by slow IV injection, or add to reservoir of a running IV infusion

Comments

Avoid direct contact with the skin

OTHER INFORMATION

Lesions of skin and oral mucosa common after full course of bleomycin

Pulmonary toxicity: interstitial pneumonia and fibrosis – most serious delayed effectIn patients with moderately severe renal impairment less than 20% of the dose is excreted in the urine

Rapid distribution to body tissues (highest concentration is in skin, lungs, peritoneum and lymph)

Inactivation takes place primarily in the liver. Approximately 60–70% of drug is excreted unchanged in the urine, probably by glomerular filtration

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