BUSULFAN INJECTION SOLUTION

Country: Canada

Language: English

Source: Health Canada

Active ingredient:

BUSULFAN

Available from:

APOTEX INC

ATC code:

L01AB01

INN (International Name):

BUSULFAN

Dosage:

60MG

Pharmaceutical form:

SOLUTION

Composition:

BUSULFAN 60MG

Administration route:

INTRAVENOUS

Units in package:

100

Prescription type:

Prescription

Therapeutic area:

ANTINEOPLASTIC AGENTS

Product summary:

Active ingredient group (AIG) number: 0103273002; AHFS:

Authorization status:

APPROVED

Authorization date:

2018-02-16

Summary of Product characteristics

PRODUCT MONOGRAPH
PR
BUSULFAN INJECTION
6 MG/ML BUSULFAN PER VIAL
STERILE SOLUTION
ANTINEOPLASTIC
APOTEX INC.
DATE OF PREPARATION
150 SIGNET DRIVE
February 15, 2018
WESTON, ONTARIO
M9L 1T9
CONTROL NUMBER: 205892
PRODUCT MONOGRAPH
Busulfan Injection 6 mg / mL
BUSULFAN
INJECTION
(BUSULFAN)
IS
A
POTENT
CYTOTOXIC
DRUG
THAT
RESULTS
IN
PROFOUND
MYELOSUPPRESSION
AT
THE
RECOMMENDED
DOSAGE. IT
SHOULD
BE
ADMINISTERED
UNDER
THE
SUPERVISION
OF
A
QUALIFIED
PHYSICIAN
WHO
IS
EXPERIENCED
IN
THE
USE
OF
CANCER
CHEMOTHERAPEUTIC AGENTS AND IN THE MANAGEMENT OF PATIENTS WITH
SEVERE
PANCYTOPENIA.
APPROPRIATE
MANAGEMENT
OF
THERAPY
AND
COMPLICATIONS
IS
ONLY
POSSIBLE
WHEN
ADEQUATE
DIAGNOSTIC
AND
TREATMENT FACILITIES ARE
READILY AVAILABLE.
ACTIONS AND CLINICAL PHARMACOLOGY
Busulfan
is
a
potent
cytotoxic
agent
and
a
bifunctional
alkylating
agent.
In
aqueous
media,
release of the methanesulfonate group produces carbonium ions, which
can alkylate
DNA, thought to be an important biological mechanism for its cytotoxic
effect.
Current literature suggests that high AUC values (>1,500 μMol•min)
may be associated with
an
increased risk of developing hepatic veno-occlusive disease and/or
seizures.
Mean C
max
, AUC, T
1/2
and plasma clearance are provided below for oral busulfan and
Busulfan (See PHARMACOLOGY).
PARAMETER
ORAL BUSULFAN
BUSULFAN
C
max
(ng/mL) (range) (CV%)
870 (30%)
1,167 (12%)
AUC (μMol•min) (CV%)
1,396 (24%)
1,156 (14%)
T
1/2
(hr) (CV%)
3.55 (33%)
3.11 (10%)
Plasma Clearance (mL/min) (CV%)
195 (27%)
182 (16%)
Intravenous
busulfan had a
more consistent pharmacokinetic
profile than oral busulfan
among patients.
Busulfan achieves concentrations in the cerebrospinal fluid
approximately equal to those
in
plasma. Irreversible binding to plasma elements, primarily albumin,
has been estimated to
be 32.4 + 2.2%, which is consistent with the reactive electrophilic
properties of this alkylator.
Busulfan
is
predominately
metabolized
through
conjugation
with
glutathione,
both
spontaneously and through glutathione S-transferase (GST).
INDIC