MYLAN-ATOVAQUONE/PROGUANIL TABLET

Country: Canada

Language: English

Source: Health Canada

Active ingredient:

ATOVAQUONE; PROGUANIL HYDROCHLORIDE

Available from:

MYLAN PHARMACEUTICALS ULC

ATC code:

P01BB51

INN (International Name):

PROGUANIL AND ATOVAQUONE

Dosage:

250MG; 100MG

Pharmaceutical form:

TABLET

Composition:

ATOVAQUONE 250MG; PROGUANIL HYDROCHLORIDE 100MG

Administration route:

ORAL

Units in package:

100

Prescription type:

Prescription

Therapeutic area:

ANTIMALARIALS

Product summary:

Active ingredient group (AIG) number: 0250721002; AHFS:

Authorization status:

APPROVED

Authorization date:

2013-02-22

Summary of Product characteristics

1
PRODUCT MONOGRAPH
PR
MYLAN-ATOVAQUONE/PROGUANIL
(250 mg Atovaquone + 100 mg Proguanil Hydrochloride)
Tablets
ANTIMALARIAL AGENT
Mylan Pharmaceuticals ULC
85 Advance Road
Etobicoke, Ontario
M8Z 2S6
SUBMISSION CONTROL NUMBER: 188695
Date of Revision:
April 20, 2016
2
PRODUCT MONOGRAPH
PR
MYLAN-ATOVAQUONE/PROGUANIL
(250 mg Atovaquone + 100 mg Proguanil Hydrochloride)
Tablets
ANTIMALARIAL AGENT
ACTIONS AND CLINICAL PHARMACOLOGY
ACTIONS
The constituents of MYLAN-ATOVAQUONE/PROGUANIL (a fixed combination
product with
each tablet containing atovaquone and proguanil hydrochloride),
interfere with two different
pathways involved in the biosynthesis of pyrimidines required for
nucleic acid replication. The
mechanism of action of atovaquone against _P.falciparum_ is via
inhibition of mitochondrial
electron transport, at the level of the cytochrome bc1 complex, and
collapse of mitochondrial
membrane potential. One mechanism of action of proguanil, via its
metabolite cycloguanil, is
inhibition of dihydrofolate reductase, which disrupts deoxythymidylate
synthesis. Proguanil also
has antimalarial activity independent of its metabolism to
cycloguanil, and proguanil, but not
cycloguanil, is able to potentiate the ability of atovaquone to
collapse mitochondrial membrane
potential in malaria parasites. This latter mechanism may explain the
synergy seen when
atovaquone and proguanil are used in combination.
Both atovaquone and proguanil are active against the hepatic stages of
_P.falciparum_ and against
asexual blood stage malarial parasites.
CLINICAL PHARMACOLOGY
PHARMACOKINETICS
There are no pharmacokinetic interactions between atovaquone and
proguanil at the
recommended dose. A population pharmacokinetic analysis in adults and
children was used to
characterize the pharmacokinetics of atovaquone and proguanil. In
clinical trials, trough levels of
atovaquone, proguanil and cycloguanil in children (weighing 11- 40 kg)
are within the range
observed in adults after adjusting for body weight.
Table 1 summarizes the pharmacokinetic pa