SPEAKER_00
0:09
Welcome
to
Drug
Safety
Matters,
a
podcast
by
Uppsala
Monitoring
Center,
where
we
explore
current
issues
in
pharmacovigilance
and
patient
safety.
My
name
is
Federica
Santoro,
and
this
episode
is
part
of
the
Uppsala
Reports
Long
Reads
series,
where
we
select
the
most
topical
stories
from
our
magazine,
Uppsala
Reports,
and
bring
them
to
you
in
audio
format.
Our
pick
for
today
is
the
article
Africa
Integral
to
Evolution
of
Pharmacogenomics
Research,
which
appeared
online
in
October
2020
and
in
print
in
issue
83
of
the
magazine.
As
the
cradle
of
modern
humanity,
the
African
continent
is
home
to
populations
with
high
levels
of
genetic
diversity.
This
diversity
has
implications
for
the
safety
and
efficacy
of
many
drugs.
But
sadly,
African
patients
remain
underrepresented
in
drug
studies.
In
fact,
of
more
than
400
medicines
with
pharmacogenetics
information
and
public
guidelines
available,
only
15
have
been
studied
in
African
populations.
Thankfully,
efforts
to
boost
pharmacogenomics
research
in
Africa
are
now
underway.
Here's
the
full
story
written
by
scientific
writer
Alexandra
Coutinho.
Although
populations
living
in
Africa
make
up
10%
of
the
world
population,
Africa
carries
25%
of
the
global
disease
burden.
Infectious
diseases
such
as
malaria,
HIV,
and
tuberculosis
are
leading
causes
of
mortality
in
Africa.
And
due
to
changes
to
a
more
Western
lifestyle,
non-communicable
diseases
such
as
cardiovascular
disease
are
increasingly
contributing
to
the
disease
burden.
The
use
of
medicines
such
as
antiretroviral
drugs
to
treat
infectious
diseases
has
had
both
positive
and
negative
consequences
for
African
patients.
While
their
use
has
contributed
to
an
increase
in
recovery
rates
and
an
overall
reduction
in
mortality
from
these
diseases,
it
has
also
caused
an
increase
in
the
incidence
of
adverse
drug
reactions
in
hospitals.
In
fact,
80%
of
recorded
adverse
events
in
Africa
are
due
to
antiretrovirals,
and
adverse
drug
reactions
are
5
to
10%
higher
in
African
populations
than
in
the
rest
of
the
world.
HIV
is
one
of
the
leading
causes
of
death
in
Africa
and
is
treated
using
antiretroviral
drugs
such
as
ifaverens
and
dolutegra.
However,
these
drugs
may
be
harmful
depending
on
how
the
body
metabolizes
them.
So
it
is
important
to
determine
the
correct
dosage
for
effective
treatment
with
minimum
side
effects.
And
this
is
where
genetic
variation
complicates
the
picture.
Ifavarens
is
metabolized
in
the
liver
by
a
genetically
polymorphic
drug
metabolizing
enzyme
called
CYP2B6.
The
frequencies
of
the
CYP2B6
G516T
genotype,
which
is
associated
with
blood
plasma
effaverens
concentration
in
non-African
populations,
have
been
used
to
calculate
the
optimal
treatment
dosage
for
this
drug.
While
this
dosage
calculation
method
is
effective
for
other
world
populations,
studies
on
efavorens
in
African
populations
found
that
50%
of
African
patients
had
effaverence
concentrations
above
that
of
the
minimum
toxic
threshold.
Dr.
Afef
Lamzouri,
a
medical
geneticist
based
at
the
Moroccan
Pharmacovigilance
Center,
is
also
the
deputy
chair
of
the
recently
formed
Pharmacogenomics
Special
Interest
Group
within
the
International
Society
of
Pharmacovigilance.
She
explains
that
the
importance
of
another
gene,
CYP2D6,
is
also
hard
to
overstate.
CYP2D6
is
responsible
for
the
metabolism
of
approximately
25%
of
all
drugs,
and
other
CYP2D6
genetic
variants
in
African
patients
may
explain
several
cases
of
resistance
or
toxicity
to
other
drugs,
such
as
codeine
and
antidepressants,
Lamzori
says.
The
drug
isoniazid
may
also
cause
more
harm
in
African
patients.
Isoniazid
is
used
as
a
treatment
for
tuberculosis,
another
of
the
deadliest
diseases
affecting
Africans,
but
is
also
associated
with
liver
toxicity
due
to
variation
in
the
gene
coding
for
the
drug
metabolizing
enzyme
N-acetyltransferase
II
or
NAT2.
Genetic
variation
in
NATII
is
classed
into
three
types
of
enzymes
based
on
the
speed
with
which
they
metabolize
drugs.
Slow,
intermediate,
and
fast
acetylators.
Patients
with
a
slow
NAT2
genotype
are
at
high
risk
of
developing
toxicity
to
isoniazid.
Studies
investigating
the
frequency
of
this
genotype
in
Moroccan
patients,
for
example,
have
found
that
over
70%
have
the
slow
acetylator
NATO
genotype
and
are
therefore
far
more
sensitive
to
lower
doses
of
isoniazid,
Lamzori
says,
adding
that
such
findings
highlight
the
urgency
for
the
development
of
genotype
guided
dosing
specifically
for
African
populations.
In
non-communicable
diseases
too,
pharmacogenomic
factors
can
be
important
considerations
in
determining
effective
drug
dosage.
For
example,
warfarin,
an
anticoagulant,
is
one
of
the
main
medications
used
to
treat
cardiovascular
disease.
A
patient's
response
to
warfarin,
and
therefore
its
dosage,
is
highly
dependent
on
certain
genetic
markers,
the
most
notable
being
the
CYP2C9
and
V
Cork
I
genes.
Yet,
as
Africans
have
the
highest
genetic
diversity
of
all
world
populations,
research
has
found
that
the
typical
genetic
markers
used
to
gauge
warfarin
dosage
and
response
in
other
world
populations
are
not
so
effective
when
applied
to
African
populations.
This
is
also
the
case
between
different
ethnic
groups
within
the
African
continent.
In
the
Moroccan
Pharmacovigilance
Center,
we
receive
a
lot
of
notifications
regarding
serious
drug
eruptions
or
skin
reactions
from
medicines
such
as
antiepileptics
and
allopurinol.
And
many
African
countries
report
the
same
high
frequency
of
these
drug
eruptions.
It
is
imperative
to
carry
out
pharmacogenomics
studies
to
explain
this
high
prevalence
in
African
populations
compared
to
other
populations,
Lamzourie
says.
And
here
we
come
to
the
crux
of
the
problem.
Despite
Africans
being
the
most
genetically
diverse
humans
in
the
world,
they
are
also
the
most
understudied
populations
in
the
world.
A
study
exploring
drug
metabolizing
enzyme
genes
across
the
world
found
that
African
populations
show
greater
genetic
diversity
than
the
rest
of
the
world's
populations.
But
the
extent
of
this
pharmacogenetic
variation
in
African
populations
is
unknown.
And
of
the
more
than
four
hundred
medicines
with
available
pharmacogenetics
information
and
public
guidelines,
only
fifteen
have
been
studied
in
African
populations,
of
which
there
is
an
average
of
only
one
to
three
studies
available
on
each
one
for
the
whole
continent,
comprising
54
countries.
This
dearth
of
research
has
huge
implications,
not
only
for
the
successful
treatment
of
disease
in
Africa,
but
for
pharmacogenomics
knowledge
in
general.
As
modern
humans
first
evolved
in
Africa,
the
discovery
of
genetic
markers
involved
in
drug
response
in
African
populations
could
be
incredibly
valuable
for
the
rest
of
the
world.
Pharmacogenomics
research
in
Africa
has
been
restricted
by
a
lack
of
funding,
education
in
pharmacology
and
personalized
medicine,
and
the
limited
capacity
of
many
clinical
practices
on
the
continent.
Nevertheless,
different
initiatives
have
been
started
over
the
last
decade
to
rectify
these
issues.
The
H3
Africa
and
Malaria
Gen
projects
were
established
to
study
genetic
variation
related
to
disease
susceptibility
in
African
populations.
Although
they
are
not
directly
involved
in
pharmacogenomics,
these
projects
have
already
increased
the
understanding
of
pharmacogenetic
variants
in
African
populations
and
have
increased
the
amount
of
African
genetic
data
available
for
pharmacogenomics
research.
One
of
the
most
important
initiatives
to
date
has
been
the
creation
of
the
African
Pharmacogenomics
Consortium,
or
APC,
in
2018.
The
APC
is
led
by
Professor
Kolle
Dandara,
a
principal
investigator
of
the
pharmacogenomics
and
drug
metabolism
research
group
at
the
University
of
Cape
Town
to
drive
pharmacogenomics
research
in
Africa
and
improve
the
safety
of
drugs
for
use
in
African
populations.
The
APC
plans
to
raise
awareness
of
pharmacogenomics
among
Africans
and
train
African
researchers
and
clinicians
to
carry
out
clinical
trials
in
African
populations
and
conduct
more
of
their
own
research
into
pharmacogenomics
in
Africa.
The
consortium
also
aims
to
increase
the
capacity
for
pharmacogenomics
in
Africa
by
developing
biobanks
and
repositories
to
support
pharmacogenomics
research,
as
well
as
implementing
better
systems
where
genetic
data
may
be
stored,
shared,
and
used
in
collaborations
between
African
and
international
researchers.
Likewise,
the
Global
Alliance
for
Genomics
and
Health
aims
to
enable
the
safe
and
effective
sharing
of
genomic
and
health-related
data
between
different
research
and
healthcare
institutions,
and
its
formation
has
been
identified
by
other
lead
African
pharmacogenomics
researchers
as
another
important
milestone
on
Africa's
path
to
personalized
medicine.
There
is
a
long
road
ahead
for
African
pharmacogenomics
to
catch
up
to
that
of
the
rest
of
the
world,
but
its
researchers
are
rising
to
the
challenge.
With
the
recent
formation
of
initiatives
like
the
APC,
the
future
may
hold
some
exciting
discoveries
that
will
propagate
the
entire
pharmacogenomics
field.
Most
importantly,
a
boost
in
pharmacogenomics
research
in
Africa
will
improve
the
treatment
outcome
for
millions
of
Africans
suffering
from
infectious
and
non-communicable
diseases,
so
that
Africa
will
no
longer
carry
a
quarter
of
the
world's
disease
burden.org.
If
you'd
like
pharmacovigilant
stories
like
this
one
delivered
straight
to
your
inbox
every
month,
sign
up
for
our
free
newsletter
at
upsalareports.org
forward
slash
subscribe.
If
you
like
drug
safety
matters,
subscribe
to
within
your
favorite
podcast
player
and
leave
us
a
review
so
other
listeners
can
find
us.
You
can
send
any
comments
or
suggestions
for
the
show
on
social
media.
Look
for
Uppsala
Monitoring
Center
on
Facebook,
LinkedIn,
or
Twitter
and
connect
to
us
there.
For
Drug
Safety
Matters,
I'm
Federica
Santoro.
I'd
like
to
thank
Matthew
Barwick
for
post
production
support
and
you
for
listening.
Till
next
time.
.jpg)
