ETHYOL - PWS IV 500MG/VIAL POWDER FOR SOLUTION

Country: Canada

Language: English

Source: Health Canada

Active ingredient:

AMIFOSTINE

Available from:

MEDIMMUNE ONCOLOGY, INC.

ATC code:

V03AF05

INN (International Name):

AMIFOSTINE

Dosage:

500MG

Pharmaceutical form:

POWDER FOR SOLUTION

Composition:

AMIFOSTINE 500MG

Administration route:

INTRAVENOUS

Units in package:

500MG

Prescription type:

Prescription

Therapeutic area:

MISCELLANEOUS THERAPEUTIC AGENTS

Product summary:

Active ingredient group (AIG) number: 0128595001; AHFS:

Authorization status:

CANCELLED POST MARKET

Authorization date:

2008-01-01

Summary of Product characteristics

(Final, Non-Annotated Version)
PRODUCT MONOGRAPH
ETHYOL
®
(AMIFOSTINE) FOR INJECTION
500 MG/VIAL
THERAPEUTIC CLASSIFICATION
CYTOPROTECTIVE AGENT
DATE OF PREPARATION:
MedImmune Oncology, Inc.
April 7, 2000
35 West Watkins Mill Road
Gaithersburg, MD 20878
DATE OF REVISION:
USA
November 12, 2003
CONTROL# 086105
1
PRODUCT MONOGRAPH
ETHYOL
®
(AMIFOSTINE) FOR INJECTION
THERAPEUTIC CLASSIFICATION
CYTOPROTECTIVE AGENT
ACTIONS AND CLINICAL PHARMACOLOGY
Amifostine is a prodrug that is dephosphorylated at the tissue site by
membrane-bound
alkaline phosphatase
1
to a pharmacologically active metabolite, the free thiol (WR-1065),
which has been shown to reduce the toxic effects of cisplatin and
radiation on normal tissue.
The ability of amifostine to selectively protect normal tissues is
based upon the differential
metabolism, and uptake of the free thiol into normal versus malignant
tissues.
2,3
This
differential effect is attributed to the higher capillary alkaline
phosphatase activity, as well
as higher pH and better vascularity of normal tissues relative to
tumor tissue.
4,5
This results
in a more rapid generation of the active free thiol metabolite as well
as a higher rate constant
for uptake into normal tissues. In addition, cell culture studies have
shown that amifostine
uptake by normal tissues occurs through facilitated uptake against a
concentration gradient,
whereas tumor tissue relies on passive, non-facilitated uptake. The
higher concentration of
free thiol in normal tissues is available to bind to, and thereby
detoxify the reactive species
of alkylating and platinum agents, as well as act as a scavenger of
oxygen free radicals.
Amifostine has been shown to reduce nephrotoxicity following
administration of single and
multiple doses of cisplatin; and, to reduce radiation-induced
toxicities to salivary tissues.
Clinical pharmacokinetic studies show that amifostine is rapidly
cleared from the plasma
with an t½
"
of <1 minute and a t½
$
of approximately 8 minutes.
6,7
Less than 10% of
amifostine remains in the pl