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New Zealand Data Sheet
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APO-AMOXI
APOTEX NZ LTD
Amoxicillin trihydrate
trihydrate equivalent to Amoxicillin 250mg and 500mg capsules
Presentation
APO-AMOXI 250mg
capsules), imprinted
imprinted 'APO 250'. Each
Each
APO-AMOXI
250mg capsules
capsules are
are red
red and
and gold
gold (size 22 capsules),
capsule
contains amoxicillin
amoxicillin trihydrate
trihydrate equivalent
equivalent to
to 250mg
250mg of amoxicillin,
capsule contains
amoxicillin, and typically
typically weighs
weighs
376mg.
APO-AMOXI 500mg
capsules), imprinted
imprinted 'APO 500'. Each
Each
APO-AMOXI
500mg capsules
capsules are
are red
red and
and gold
gold (size 00 capsules),
capsule contains
amoxicillin, and typically
typically weighs
weighs
capsule
contains amoxicillin
amoxicillin trihydrate
trihydrate equivalent
equivalent to
to 500mg
500mg of amoxicillin,
735mg.
Indications
Treatment of infection
indicated in
in the
the treatment
treatment of
of infections
infections due
due to susceptible organisms.
APO-AMOXI isisindicated
APO-AMOXI may
useful in
in instituting
instituting therapy
therapy prior
prior to
to bacteriology;
bacteriology; however
however bacteriological
bacteriological
APO-AMOXI
may be useful
studies to determine
determine the causative
causative organisms
organisms and
their sensitivity
sensitivity to amoxicillin
amoxicillin should
should be
studies
and their
performed.
Prophylaxis for endocarditis
APO-AMOXI may be used for the prevention of bacteraemia, associated with procedures such as
dental extraction, in patients at risk of developing bacterial endocarditis.
Dosage and Administration
This product is not able to deliver all approved dose regimens.
Upper respiratory tract infections, Genito-urinary tract infections, skin and soft
tissue infections
For upper
upper respiratory
respiratory tract
tract infections
infections due
duetotostreptococci,
streptococci,pneumococci,
pneumococci,non-penicillinasenon-penicillinaseFor
producing staphylococci and H. influenzae) or Genito-Urinary Tract Infections (due to Escherichia
coli, Proteus
Proteus mirabilis
mirabilis and Streptococcus
Streptococcus faecalis
faecalis or Skin
Skin and
and Soft
Soft Tissue
Tissue Infections
Infections due
due to
coil,
Escherichia coil:
coli:
streptococci, sensitive staphylococci and Escherichia
Adults: 250 mg every
every 8 hours.
hours. Children
Children (under
(under 20 kg):
kg): 25
25 mg/kg/day
mg/kg/day in
in equally
equally divided
divided doses
doses
Adults:
every 8 hours.
severe infections
infections or those caused
caused by less susceptible
susceptible organisms,
hours for
In severe
organisms, 500
500 mg
mg every
every 88 hours
adults and 50 mg/kg/day in equally divided doses every 8 hours for children may be needed.
Lower respiratory tract infections
For lower
lower respiratory
respiratory tract
tract infections
infections (due
(duetotostreptococci,
streptococci,pneumococci,
pneumococci, non-penicillinase
non-penicillinase
For
influenzae:
producing staphylococci and H. influenzae:
Adults: 500 mg every
every 8 hours.
hours. Children
Children (under
(under 20 kg):
kg): 50
50 mg/kg/day
mg/kg/day in
in equally
equally divided
divided doses
doses
Adults:
every 8 hours.
High dosage therapy
The maximum recommended oral dosage 6 g daily in divided doses. An adult dosage of 3 g twice
daily is recommended
recommended in
appropriate cases
treatment of severe
severe or
or recurrent
recurrent purulent
purulent
daily
in appropriate
cases for
for the treatment
infection of the respiratory tract.
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 1 of 13
A
APOTEX NZ LTD
APO-AMOXI
Amoxicillin trihydrate
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin
trihydrate equivalent
Prophylaxis of Endocarditis - Dental Procedures
Prophylaxis for patients undergoing
undergoing extraction,
Prophylaxis
extraction, scaling
scaling or surgery involving gingival tissues who
the previous
previous month. Patients with prosthetic heart valves should
have not received a penicillin in the
be referred to hospital (see below).
Patient not having a general anaesthetic
Adults –
hour before
before procedure.
hours later
Adults
—33 gg orally,
orally, 11 hour
procedure. AA second
second dose
dose may
may be
be given
given 66 hours
later if
considered necessary.
considered
necessary. Children
Children under
under 10
10 -- half
half the
the adult
adult dose.
dose. Children
Children under
under 55 - quarter adult
dose.
Patients having a general anaesthetic, oral antibiotics considered to be appropriate
Adults -- initially
initially 3
orally 44 hours
hours prior
prior to
to anaesthesia
anaesthesia followed
orally (or
(or 1 g
Adults
3 gg orally
followedby
by 33 g orally
amoxicillin/ampicillin IM
amoxicillin/ampicillin
IM ifif the
the dose
dose is not tolerated) 6 hours after the initial dose. Children under
10 - half adult dose. Children under 5 - quarter adult dose.
Patient having general anaesthesia, oral antibiotics not appropriate
Adults—
– 1 g amoxicillin IM immediately before induction with 500 mg orally 6 hours later. Children
Adults
under 10 - half adult dose.
Note:
Note: If prophylaxis
prophylaxis with
with amoxicillin
amoxicillin is given
given twice
twice within
within one
one month,
month, emergence
emergence of resistant
resistant
streptococci is
unlikely to
be aaproblem.
problem. Alternatively,
Alternatively, antibiotics
antibiotics are
are recommended
recommended if more
more
streptococci
is unlikely
to be
frequent prophylaxis is required, or the patient has received a course of treatment with a penicillin
during the previous month.
Patients for whom referral to hospital is recommended
Patients to be given a general anaesthetic who have been given a penicillin in the previous
month.
Patients to be given a general anaesthetic who have a prosthetic heart valve.
Patients who have had one or more attacks of endocarditis.
Adults
with 120
120 mg
mg gentamicin
IM immediately
prior to
Adults - Initially
Initially 1 g amoxicillin/ampicillin
amoxicillin/ampicillin with
gentamicin IM
immediately prior
anaesthesia (if given) or 15 minutes prior to dental procedure, followed by 500 mg APO-AMOXI
APO-AMOXI
anaesthesia
orally, 6 hours later.
Children under 10 - the dose of amoxicillin should be half the adult dose. The dose of gentamicin
should be 2 mg/kg.
Note: Amoxicillin
Amoxicillin and
Note:
and gentamicin
gentamicin should
should not
not be
be mixed
mixed in the same syringe. Please consult the
appropriate Data Sheet for parenteral amoxicillin and gentamicin.
Urethritis (due to Neisseria gonorrhoeae)
single dose.
dose. Cases
Cases of gonorrhoea
gonorrhoea with a suspected
suspected lesion of syphilis should have
Adults: 3 g as single
dark field examinations before receiving amoxicillin and monthly serological
serological tests
tests for a minimum
of four months.
Lower urinary tract infections
coli, Proteus mirabilis,
For acute, uncomplicated lower urinary tract infections (due to Escherichia coil,
Streptococcus faecalis, non-penicillinase producing staphylococci):
Adults: 3 g as a single dose.
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 2 of 13
A
APOTEX NZ LTD
APO-AMOXI
Amoxicillin trihydrate
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin
trihydrate equivalent
children's dose is intended for individuals whose
NOTE: The children's
whose weight
weight will not cause dosage to be
recommended for adults. Children weighing
calculated greater than that recommended
weighing more than 20 kg should
be dosed according to the adult recommendations.
should be
be recognised
recognised that
that in
in the
thetreatment
treatment ofofchronic
chronicurinary
urinary tract
tractinfections,
infections, frequent
frequent
It should
bacteriological and
appraisals are necessary.
necessary. Smaller doses than
than those
those recommended
recommended
bacteriological
and clinical
clinical appraisals
above should not be used. In stubborn infections, therapy
therapy may be required
required for several
several weeks. It
necessary to continue
continue clinical
clinical and/or
and/or bacteriological
bacteriological follow-up
may be necessary
follow-up for several months after
cessation of therapy.
Treatment duration
Treatment should
should be continued
continued for
for a minimum
minimum of 48 to 72 hours beyond the time that the patient
becomes asymptomatic or evidence of bacterial eradication has been obtained.
It is recommended that there be at least 10 days treatment for any infection caused by haemolytic
streptococci to prevent the occurrence of rheumatic fever or glomerulonephritis.
Impaired renal function
renal impairment
impairment the
excretion of amoxicillin
amoxicillin will
delayed. Depending
Depending on
degree of
In renal
the excretion
will be delayed.
on the
the degree
impairment, itit may
necessary to reduce
reduce the total
total daily
daily dosage.
dosage. No
No dosage
dosage adjustment
adjustment is
impairment,
may be necessary
required in patients with a creatinine clearance > 30 ml/min. The maximum recommended dose in
patients with creatinine clearance between 10 and 30 ml/min is 500 mg twice daily. The maximum
recommended dose in patients with a creatinine clearance < 10 ml/min is 500 mg/day.
patients receiving
receiving peritoneal
peritoneal dialysis,
dialysis, the maximum
maximum recommended
recommended dose
500 mg/day.
mg/day.
In patients
dose in
in 500
Amoxicillin may be removed from the circulation by haemodialysis.
Renal impairment in children under 40 kg
Creatinine clearance >30 ml/min: No adjustment necessary
Creatinine clearance
mg/kg give
give twice
twice daily
daily (maximum
(maximum 500
500 mg/twice
mg/twice
Creatinine
clearance 10
10 to
to 30 ml/min: 15 mg/kg
daily)
Creatinine clearance <10 ml/min: 15 mg/kg given as a single daily dose (maximum 500 mg)
In the majority of cases, parenteral therapy will be preferred.
Contraindications
Amoxicillin is a penicillin and should not be given to patients
patients with a history
history of
of hypersensitivity
hypersensitivity to
Amoxicillin
beta-lactam antibiotics (e.g. penicillins, cephalosporins).
contraindicated in patients
Amoxicillin is contraindicated
patients who have had previous
previous experience
experience of
of a major allergy or
anaphylaxis to a cephalosporin or penicillin.
Hypersensitivity to any of the excipients.
Warnings and Precautions
Warnings
Serious and occasionally
occasionally fatal hypersensitivity
hypersensitivity reactions
reported in
Serious
reactions (anaphylaxis)
(anaphylaxis) have
have been
been reported
patients receiving beta-lactam antibiotics. Before initiating therapy with amoxicillin, careful enquiry
should be made
made concerning
concerning previous
previous hypersensitivity
hypersensitivity reactions
reactions to
to penicillins,
penicillins, cephalosporins.
cephalosporins.
should
Cross-sensitivity between
Cross-sensitivity
between penicillins
penicillins and cephalosporins
cephalosporins is well documented. Patients should be
told about
about the potential
potential occurrence
occurrence of
allergic reactions
told
of allergic
reactions and
and instructed
instructed to
to report
report them.
them. IfIf an
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 3 of 13
A
APOTEX NZ LTD
APO-AMOXI
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin trihydrate
trihydrate equivalent
allergic reaction
reaction occurs, amoxicillin should be discontinued
discontinued and
and appropriate
appropriate alternative
alternative therapy
allergic
instituted. Serious
Serious anaphylactic
anaphylactic reactions
require immediate
immediate emergency
emergency treatment
treatment with
with
instituted.
reactions may
may require
adrenaline or epinephrine.
epinephrine. Oxygen,
Oxygen, intravenous
intravenous steroids
steroids and
and airway
airway management,
management, including
including
adrenaline
intubation, may also be required.
Amoxicillin should
with caution
caution to patients
patients with
with lymphatic
lymphatic leukaemia
leukaemia as
they are
are
Amoxicillin
should be
be given
given with
as they
susceptible to amoxicillin induced skin rashes. Amoxycillin should not be used for the treatment of
bacterial
bacterial infections
infections in
in patients
patients with
with viral infections,
infections, presenting
presenting with
with sore throat,
throat, pharyngitis
pharyngitis or
infectious mononucleosis, as a high incidence of amoxycillin induced erythematous (morbilliform)
rashes have been associated with glandular fever in patients receiving amoxicillin.
As with
with any
any potent
potent drug,
drug, periodic
periodic assessment
assessment of
of renal,
renal, hepatic
hepatic and
andhaematopoietic
haematopoietic function
function
should be made during prolonged therapy. Prolonged use may occasionally result in overgrowth
non-susceptible organisms.
superinfection with
mycotic or bacterial
bacterial
of non-susceptible
organisms. The
The possibility
possibility of
of superinfection
with mycotic
pathogens should
be particularly
particularly considered.
considered. If
If superinfection
superinfection occurs
occurs (usually
(usually involving
involving
pathogens
should be
Aerobacter, Pseudomonas or Candida) discontinue amoxicillin and/or initiate appropriate therapy.
Pseudomembranous colitis should be borne in mind if severe persistent diarrhoea occurs (in most
cases caused
caused by Clostridium
Clostridium difficile) In this
this case
case Amoxicillin
Amoxicillin should
should be discontinued
discontinued and
cases
and an
adequate therapy has to be started. The use of antiperistaltics is contraindicated.
Abnormal prolongation
been reported
reported rarely
rarely in
in patients
patients receiving
receiving
Abnormal
prolongationof
of prothrombin
prothrombintime
time has
has been
amoxicillin and
oral anticoagulants.
anticoagulants. Appropriate
Appropriate monitoring
monitoring should
undertaken when
when
amoxicillin
and oral
should be undertaken
anticoagulation treatment
the anticoagulant
anticoagulant adjusted
anticoagulation
treatment is
is prescribed
prescribed concurrently
concurrently and
and the
the dose of the
as necessary.
high doses,
doses, adequate
adequate fluid intake
intake and
and urinary
urinary output
output must
must be
be maintained
maintained to minimise
minimise the
At high
possibility of amoxicillin crystalluria.
Precaution should be taken in premature children and during neonatal period: renal, hepatic and
haematological functions should be monitored.
with other
other beta-lactams,
beta-lactams, the
the blood
blood formula
formula should
should be
be checked
checked regularly
regularly during
during high-dose
high-dose
As with
therapy.
High dose therapy
therapy with
with beta-lactams
beta-lactams for patients
patients with
with renal
renal insufficiency
insufficiency or
or seizures
seizures history,
history,
High
treated epilepsy and meningeal affection, could exceptionally lead to seizures.
The occurrence
occurrence of a generalized erythema with fever and pustules at the beginning of treatment
should make
make suspect
suspect aa generalized
generalized acute
acute exanthematic
exanthematic pustulosis;
pustulosis; this
this necessitates
necessitates the
the
should
interruption of therapy and contraindicated any further administration of amoxicillin.
Amoxicillin should
experienced symptoms of allergy
Amoxicillin
should be given with caution to patients who have experienced
associated with a cephalosporin or penicillin.
hypernatraemia. Use of a
Massive doses of amoxicillin can cause hypokalaemia and sometimes hypernatraemia.
potassium-sparing diuretic
treatment for more
potassium-sparing
diuretic may
may be
be helpful.
helpful. In patients undergoing high-dose treatment
than 5 days, electrolyte balance, blood counts and renal functions should be monitored.
Precautions
Dosage should
adjusted in
patients with
with renal
renal impairment
impairment (refer
(refer to Dosage
Dosage and
and
Dosage
should be
be adjusted
in patients
administration).
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 4 of 13
A
APOTEX NZ LTD
APO-AMOXI
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin trihydrate
trihydrate equivalent
Following single dose therapy of acute lower urinary tract infections, the urine should be cultured.
positive culture may be evidence of a complicated
complicated or upper urinary tract infection, and higher
A positive
dose or prolonged course of treatment may be appropriate.
Following
administrationofof ampicillin
ampicillin to
to pregnant
women aa transient
Following administration
pregnant women
transient decrease
decrease in plasma
plasma
concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol has
been noted. This effect may also occur with amoxicillin.
patients with reduced
reduced urine
urine output
output crystalluria
crystalluria has been
been observed
observed very
very rarely,
rarely, predominantly
predominantly
In patients
parenteral therapy.
with parenteral
therapy. During
During the
the administration
administration of
of high
high doses
doses of
of amoxicillin,
amoxicillin, itit is advisable to
maintain adequate
possibility of amoxicillin
adequate fluid
fluid intake
intake and urinary output
output in order to reduce the possibility
crystalluria (refer to Overdosage). The presence of high urinary concentrations of amoxicillin can
cause precipitation
precipitation of
product in urinary
urinary catheters.
catheters. Therefore,
Therefore, catheters
catheters should
should be visually
visually
cause
of the product
inspected at intervals.
gastrointestinal disturbances
disturbances with
diarrhoea and vomiting should
Patients suffering from severe gastrointestinal
with diarrhoea
not be
be treated
treated with
with APO-AMOXI,
APO-AMOXI, due
the risk
risk of
of reduced
reduced absorption.
absorption. In
these cases
cases a
not
due to
to the
In these
parenteral treatment with amoxicillin is advisable.
APO-AMOXI should be used with caution in patients with allergic diathesis and asthma.
Precautions should be taken for children, premature infants and during the neonatal period, renal,
hepatic and haematological functions should be monitored.
Use in Pregnancy
Category A
Assigned Category
by the
the Australian
Australian Drug
Drug Evaluation
Evaluation Committee.
Committee. This
This category
category includes
includes
Assigned
Category A
A by
medicines which
large number
number of
of pregnant
pregnant women
women and
and women
women of
medicines
which have
have been
been taken
taken by
by a large
childbearing age without any proven increase in the frequency of malformations or other direct or
amoxicillin for use in
indirect harmful
harmful effects
effects on the foetus having
having been
been observed.
observed. The
The safety
safety of amoxicillin
human pregnancy
pregnancy has
been established
established by well
well controlled
controlled studies
studies in
in pregnant
pregnant women.
women.
human
has not
not been
Reproduction studies
studies have
have been
been performed
performed in
in mice
mice and
and rats
rats at doses
doses up to ten times the human
dose and these studies have revealed no evidence of impaired fertility or harm to the foetus due
amoxicillin. Amoxicillin
Amoxicillin may
pregnancy when the
the potential
potential benefits
benefits outweigh
outweigh the
to amoxicillin.
may be used in pregnancy
potential risks associated with treatment.
Use in labour and delivery
Oral
ampicillin class antibiotics
antibiotics are generally
generally poorly absorbed
absorbed during
during labour.
labour. Studies
Studies in guinea
guinea
Oral ampicillin
pigs have
have shown
shown that
that intravenous
intravenous administration
administration of
ampicillin decreased
decreased the
uterine tone,
tone,
pigs
of ampicillin
the uterine
frequency and duration of contractions. However, it is not known whether the use of amoxicillin in
humans during
delivery has immediate
immediate or delayed
delayed adverse
adverse effects
effects on the
the foetus,
foetus,
humans
during labour
labour or
or delivery
prolongs the duration of labour or increases the likelihood that forceps delivery or other obstetrical
intervention or resuscitation of the newborn will be necessary.
Use in lactation
Residual amoxicillin may be present in breast milk at levels corresponding to approximately 0.7%
the maternal
maternal dose.
dose. Penicillins
Penicillins are
are considered
considered to
to be
be compatible
compatible with
with breastfeeding
breastfeeding although
although
of the
sensitisation. So far no
there are theoretical risks of alterations to infant bowel flora and allergic sensitisation.
detrimental effects for the breast-fed infant have been reported after taking amoxicillin. Amoxicillin
used during
during breast-feeding.
breast-feeding. However, breast-feeding must be stopped
stopped ifif gastrointestinal
gastrointestinal
can be used
disorders (diarrhoea, candidosis or skin rash) occur in the new born.
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 5 of 13
A
APOTEX NZ LTD
APO-AMOXI
Amoxicillin trihydrate
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin
trihydrate equivalent
Trace quantities
potential for hypersensitivity
hypersensitivity
quantities of penicillin can be detected in breast milk with the potential
reactions (e.g.
drug rashes)
rashes) or gastrointestinal
gastrointestinal disorders
candidosis) in
reactions
(e.g. drug
disorders (e.g.
(e.g. diarrhea
diarrhea or
or candidosis)
in the
breast-fed infant. Consequently, breastfeeding might have to be discontinued.
Effects on ability to drive and use machines
This medicine
medicine is
is presumed
presumed to
to be
be safe
safe or unlikely
unlikely to
to produce
produce and
and effect
effect on
on the
the ability
ability to
to drive or
use machinery.
During treatment
treatment with
with amoxicillin,
amoxicillin, undesirable
undesirable effects
occur (e.g.
(e.g. allergic
allergic reactions,
reactions,
During
effects may
may occur
dizziness, convulsions)
and use
use machines.
machines. Patients
Patients
dizziness,
convulsions)which
which may
may influence
influence the
the ability
ability to
to drive and
should be cautious when driving or operating machinery.
Adverse Effects
transitory nature.
Side-effects, as with other penicillins, are uncommon
uncommon and mainly of a mild and transitory
The majority
majority of the side-effects
side-effects listed
amoxicillin and may occur when
listed below
below are not unique to amoxicillin
using other penicillins.
Undesirable effects
classified systematically
frequency according
following
Undesirable
effects are
are classified
systematically and
and by
by frequency
according to
to the following
convention: very common (above 1 in 10); common (from 1 in 100 to 1 in 10); uncommon (from 1
in 1000 to 1 in 100; rare (from 1 in 10,000 to 1 in 1,000); very rare (below 1 in 10,000).
otherwise stated,
Unless otherwise
stated, the
the frequency
frequency of
of adverse
adverse events
events has
has been
been derived
derived from
from more
more than 30
years of post-marketing reports.
Haemic and the lymphatic system disorders
Very rare
Reactions such as
as anaemia,
anaemia, thrombocytopenia,
thrombocytopenia, thrombocytopenic
thrombocytopenic purpura,
purpura, eosinophilia
eosinophilia and
Reactions
leucopenia (including severe neutropenia or agranulocytosis), have been reported during therapy
with other penicillins.
penicillins. All were reversible
reversible on discontinuation
discontinuation of
believed to be
with
of therapy
therapy and
and are
are believed
hypersensitivity phenomena. Prolongation
Prolongation of bleeding
bleeding time and prothrombin time have also been
reported rarely (refer to Warnings and precautions).
Immune system disorders
Very rare
with other
other antibiotics,
antibiotics, severe
severe allergic
allergic reactions,
reactions, including
including angioneurotic
angioneurotic oedema,
oedema, anaphylaxis
anaphylaxis
As with
precautions), serum sickness and allergic vasculitis. If aa hypersensitivity
hypersensitivity
(refer to Warnings and precautions),
reaction is reported, the treatment must be discontinued. (see also Skin and subcutaneous tissue
disorders).
Infections and infestations
Uncommon
Prolonged and repeated use of the preparation can result in superinfections and colonisation with
resistant organisms or yeasts such as oral and vaginal candidiasis.
Gastrointestinal disorders
Common
Gastric
complaints, nausea,
appetite, flatulence,
flatulence, soft
soft stools,
stools, diarrhoea,
diarrhoea, enanthemas
enanthemas
Gastric complaints,
nausea, loss
loss of appetite,
(particularly in
region of the
the mouth),
mouth), dry
dry mouth,
mouth, taste
taste disturbances.
disturbances. These
These effects
effects on the
(particularly
in the
the region
gastrointestinal system
frequently disappear
treatment or
gastrointestinal
system are
are mostly
mostly mild
mild and frequently
disappear either
either during
during the treatment
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 6 of 13
A
APOTEX NZ LTD
APO-AMOXI
Amoxicillin trihydrate
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin
trihydrate equivalent
very soon after completion
completion of therapy.
therapy. The occurrence
occurrence of
effects can generally
generally be
very
of these side effects
reduced by taking amoxicillin during meals.
Uncommon
Vomiting.
Rare
Superficial discoloration
oral suspension
suspension is
used). Usually
Usually the
the
Superficial
discolorationofofthe
the teeth
teeth (especially
(especiallyifif aa oral
is used).
discoloration can be removed by teeth brushing.
Very rare
Mucocutaneous candidiasis. Antibiotic associated colitis including pseudomembranous colitis and
haemorrhagic colitis.
persistent diarrhoea
rare possibility
possibility of
haemorrhagic
colitis. IfIf severe
severe and
and persistent
diarrhoea occurs,
occurs, the
the very
very rare
pseudomembranous colitis
pseudomembranous
colitis should
should be considered.
considered. The administration
administration of anti-peristaltic agents is
contraindicated.
Development of a black hairy tongue.
General disorders and administration site conditions
Rare
Drug fever
Hepatobiliary disorders
Rare
Hepatitis and cholestatic jaundice.
Uncommon
Moderate and
Moderate
and transient
transient increase
increase of
of liver
liver enzymes.
enzymes. The
The significance
significance of
of aa rise
rise in liver enzymes is
unclear
Nervous system disorders
Rare
Hyperkinesia, dizziness
Hyperkinesia,
dizziness and
and convulsions.
convulsions. Convulsions
Convulsions may
may occur
occur in patients with impaired renal
function, epilepsy meningitis, or in those receiving high doses.
Skin and subcutaneous tissue disorders
Common
Cutaneous reactions
exanthema, pruritus,
pruritus, urticaria,
urticaria, erythematous
erythematous maculopapular rash;
Cutaneous
reactions such as exanthema,
morbilliform exanthema
days after
after commencement
commencement of therapy.
therapy. The
the typical morbilliform
exanthema occurs
occurs 55 to 11 days
immediate appearance of urticaria indicates an allergic reaction to amoxicillin and therapy should
therefore be discontinued.
Rare
Skin reactions
reactions such
such as
as Angioneurotic
Angioneurotic oedema
oedema (Quincke's
(Quincke's oedema
oedema ,, erythema
erythema multiforme
multiforme
Skin
exudativum, exsudativum,
exsudativum, acute
generalized pustulosis,
pustulosis, Lyell's
Lyell’s syndrome,
syndrome, Stevens-Johnson
Stevens-Johnson
exudativum,
acute generalized
syndrome, toxic
epidermal necrolysis,
necrolysis, bullous
dermatitis and acute
acute generalised
generalised
syndrome,
toxic epidermal
bullous and exfoliative dermatitis
exanthematous pustulosis (see also Immune system disorders).
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 7 of 13
A
APOTEX NZ LTD
APO-AMOXI
APO-AMOXI
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin trihydrate
trihydrate equivalent
Renal and urinary tract disorders
Rare
Interstitial nephritis, crystalluria (refer to Overdosage)
The
incidence of
these adverse
adverse events
derived from
clinical studies
The incidence
of these
events was
was derived
from clinical
studies involving
involving aa total
total of
approximately 6,000 adult and paediatric patients taking amoxicillin.
Reporting of suspected adverse reactions
Reporting suspected
suspected adverse
adverse reactions
reactions after
after authorisation
authorisation of
of the medicine is important. It allows
continued monitoring
benefit/risk balance
balance of the
the medicine.
medicine. Healthcare
Healthcare professionals
professionals are
continued
monitoring of
of the benefit/risk
asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.
Interactions
Medicines and other pharmacologically active substances
Concurrent administration
amoxicillin can
increase the
the
Concurrent
administrationofof allopurinol
allopurinol during
during treatment
treatment with
with amoxicillin
can increase
likelihood of allergic skin reactions.
Concomitant administration
coumarin, may increase
Concomitant
administration of
of amoxicillin
amoxicillin and
and anticoagulants,
anticoagulants, such
such as
as coumarin,
the incidence of bleeding due to prolongation of prothrombin time. Appropriate monitoring should
undertaken when
when anticoagulation
anticoagulation treatment
be undertaken
treatment is
is prescribed
prescribed concurrently
concurrentlyand
and the
the dose
dose of
of the
anticoagulant adjusted
showing an
increase of
oral
anticoagulant
adjustedas
as necessary.
necessary.AA large
large number
number of
of cases
cases showing
an increase
of oral
anticoagulant activity
reported in patients
patients receiving
receiving antibiotics.
antibiotics. The infectious
infectious and
and
anticoagulant
activity has
has been
been reported
inflammatory context,
factors. In these
inflammatory
context, age
age and
and the
the general
general status
status of
of the patient
patient appear
appear as
as risk factors.
circumstances, itit is difficult to know the part
part of
of the
the responsibility
responsibility between
between the infectious
infectious disease
circumstances,
treatment in the
the occurrence
occurrence of INR
INR disorders.
disorders. However,
However, some classes of antibiotics
antibiotics are
and its treatment
more involved,
involved, notably
notably fluoroquinolones,
fluoroquinolones, macrolides,
macrolides, cyclines,
cyclines, cotrimoxazole
cotrimoxazole and
some
more
and some
cephalosporins
There
possibility that
that the
the bactericidal
bactericidal action
action of amoxicillin
amoxicillin could
could be antagonised
antagonised on
There is aa possibility
on coadministration with
bacteriostatic agents
such as
as macrolides,
macrolides, tetracyclines,
tetracyclines, sulphonamides
sulphonamides or
administration
with bacteriostatic
agents such
chloramphenicol.
is possible
possible on
on concurrent
concurrent administration
administration with amoxicillin.
An increase in the absorption of digoxin is
A dose adjustment of digoxin may be necessary Interaction between amoxicillin and methotrexate
leading to methotrexate toxicity has been reported. Serum methotrexate levels should be closely
monitored
monitored in patients
patients who
who receive
receive amoxicillin
amoxicillin and
andmethotrexate
methotrexate simultaneously.
simultaneously. Amoxicillin
Amoxicillin
decreases the renal clearance of methotrexate,
methotrexate, probably
competition at the common tubular
decreases
probably by competition
secretion system.
Probenecid decreases
Probenecid
decreases the
the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin
may result in increased and prolonged levels of amoxicillin in serum and bile.
Administration of
estrogens and
and
Administration
of amoxicillin
amoxicillin can
can transiently
transiently decrease
decreasethe
the plasma
plasma level
level of estrogens
progesterone, and may reduce the efficacy of oral contraceptives. It is therefore recommended to
take supplemental non-hormonal contraceptive measures.
Forced diuresis
reduction in
in blood
bloodconcentrations
concentrations by
by increased
increased elimination
elimination of
Forced
diuresis leads
leads to
to aa reduction
amoxicillin.
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Page 8 of 13
A
APOTEX NZ LTD
APO-AMOXI
Amoxicillin trihydrate
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin
trihydrate equivalent
is recommended
recommended that
that when
when testing
testing for the
the presence
presence of
of glucose
glucose in
in urine
urine during
during amoxicillin
amoxicillin
It is
treatment, enzymatic
the high
high urinary
urinary
treatment,
enzymaticglucose
glucoseoxidase
oxidasemethods
methodsshould
shouldbebeused.
used.Due
Due to
to the
concentrations of amoxicillin, false positive readings are common with chemical methods.
The occurrence of diarrhoea may impair the absorption
absorption of other
other medicines
medicines consequently
consequently limiting
their efficacy.
Amoxicillin may decrease the amount of urinary estriol in pregnant women.
At high concentrations, amoxicillin may diminish the results of serum glycaemia levels
Amoxicillin may interfere with protein testing when colorimetric methods are used
Abnormal laboratory test results
At high
high risk
risk concentrations,
concentrations, amoxicillin
amoxicillin may diminish
glycaemia levels.
diminish the
the results
results of serum glycaemia
levels. It is
recommended that when testing for the presence of glucose in urine during amoxicillin treatment,
enzymatic glucose
urinary concentrations
concentrations of
enzymatic
glucose oxidase
oxidase methods
methods should
should be
be used.
used. Due
Due to the high urinary
amoxicillin, false positive readings are common with chemical methods.
Amoxicillin may interfere with protein testing when colorimetric methods are used.
Penicillins may interfere with:
- Urinary glucose test
- Coomb’s
Coomb's tests
tests
- Tests for urinary or serum proteins
- Tests which use bacteria e.g. Guthrie test.
Overdosage
Signs and symptoms
Cases of overdosage
overdosage with
with amoxicillin
amoxicillin are
are usually
usuallyasymptomatic.
asymptomatic. Gastrointestinal
Gastrointestinal disturbances
disturbances
Cases
such as nausea,
nausea, vomiting
vomiting and
and diarrhoea
diarrhoea and
and symptoms
symptoms of
of fluid-electrolyte
fluid-electrolyte imbalance
imbalance may
such
may be
evident. In patients with severely impaired
evident.
impaired renal
renal function,
function, large
large overdoses
overdoses can
can result
result in
in signs
signs of
administration of high doses of amoxicillin,
amoxicillin,
renal toxicity and crystalluria is possible. During the administration
adequate fluid
urinary output
output must
must be maintained
maintained to minimise
minimise the possibility
possibility of
adequate
fluid intake
intake and
and urinary
amoxicillin crystalluria.
Management
There
no specific
specific antidote
antidote for
for an
an overdose
overdose of
ofamoxicillin.
amoxicillin. Treatment
Treatment consists
consists primarily
primarily of
There is no
administration of
gastric lavage is usually
usually not necessary),
necessary), or symptomatic
symptomatic
administration
of activated
activated charcoal
charcoal (a gastric
supportive measures.
and electrolyte
electrolyte
and supportive
measures. Particular
Particular attention
attention should
should be
be directed
directed to
to the
the water and
balance of the patient. Amoxicillin can be removed from the circulation by haemodialysis.
For advice on the management of overdose, please contact the National Poisons Centre on 0800
POISON (0800 764766).
Further Information
Actions
Amoxicillin is an aminobenzyl
aminobenzyl penicillin
bactericidal action
inhibition of the
Amoxicillin
penicillin that
that has
has a bactericidal
action due
due to
to its inhibition
bactericidal effect against many Gram-positive and
synthesis of the bacterial cell wall. It exerts a bactericidal
Gram-negative
effective against
against beta-lactamase
beta-lactamase producing
producing
Gram-negative microorganisms.
microorganisms. Amoxicillin
Amoxicillin isis not effective
organisms.
Please refer to Medsafe website (www.medsafe.govt.nz) for the most recent datasheet
Page 9 of 13
A
APOTEX NZ LTD
APO-AMOXI
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin trihydrate
trihydrate equivalent
Pharmacotherapeutic group
J01CA04
JO1CA04 –—Penicillins
Penicillinswith
withextended
extendedspectrum,
spectrum, amoxicillin.
amoxicillin.
Mechanism of action
Beta-lactam antibiotic.
Pharmacodynamic effects
Inhibition of bacterial cell wall synthesis.
Antibiotic class
Amoxicillin is a semi-synthetic aminopenicillin of the beta-lactam group of antibiotics.
Antibiotic nature and mode of action
Amoxicillin has a broad spectrum of antibacterial activity against many Gram-positive and Grammicroorganisms, acting
biosynthesis of cell wall
wall mucopeptide.
mucopeptide.
negative microorganisms,
acting through
through the
the inhibition
inhibition of biosynthesis
Amoxicillin
Amoxicillin is active
active in vitro
vitro against
against beta-lactamase
beta-lactamase negative
mirabilis, and
negative strains
strains of Proteus mirabilis,
Haemophilus
Haemophilus influenza.
influenza. In vitro studies
studies have also demonstrated
demonstrated activity
activity against
against most
most strains
strains of
alpha- and
and beta-haemolytic
beta-haemolytic streptococci.
streptococci. Streptococcus
Streptococcus pneumoniae,
pneumoniae, and beta-lactamase
beta-lactamase
alphanegative strains
strains of
of staphylococci,
staphylococci, Neisseria
Neisseria gonorrhoeae,
gonorrhoeae, Neisseria
Neisseria meningitidis
meningitidis and
negative
Enterococcus faecalis.
faecalis. However,
However, some
organisms are
are sensitive
sensitive to amoxicillin
amoxicillin only
Enterococcus
some of
of the organisms
only at
concentrations achieved in the urine. Strains of gonococci which are relatively resistant to benzyl
penicillin may also be resistant to amoxicillin.
Amoxicillin is susceptible to degradation by beta-lactamases and therefore it is ineffective against
bacteria which
which produce
produce these enzymes
enzymes particularly
particularly resistant
bacteria
resistant staphylococci,
staphylococci, which
which now
now have
have a
high prevalence.
prevalence. All
strains of Pseudomonas,
Pseudomonas, Klebsiella
Klebsiella and Enterobacter, indole
indole positive
positive
high
All strains
Proteus, Serratia
Serratia marcescens,
marcescens, Citrobacter,
penicillinase producing
producing N. gonorrhoeae
gonorrhoeae and
Citrobacter, penicillinase
penicillinase producing H. influenzae
influenzae are also
also resistant.
resistant. Escherichia coli isolates are becoming
becoming
increasingly resistant to amoxicillin in vitro due to the presence of penicillinase-producing strains.
Susceptibility
The prevalence
prevalence of
resistance may
geographically and
selected species and
of resistance
may vary geographically
and with
with time for selected
local information
information on
resistance is desirable,
desirable, particularly
particularly when
when treating
treating severe
severe infections.
infections. As
local
on resistance
necessary, expert
prevalence of resistance
resistance is such that
necessary,
expert advice
advice should
should be
be sought
sought when
when the local prevalence
the utility of the agent in at least some types of infections is questionable.
Breakpoints
The MIC breakpoints
breakpoints for susceptible
susceptible organisms
organisms vary
vary according
according to
to species.
species. Enterobacteriaceae
Enterobacteriaceae
amoxicillin and resistant
are considered susceptible
susceptible when
when inhibited
inhibited at
at NMT
NMT 8 mcg/ml amoxicillin
resistant at NLT 32
mcg/ml.
From NCCLS
NCCLS recommendations
recommendations and using
using NCCLS-specified
NCCLS-specified methods,
methods, M. catarrhalis
catarrhalis (betaFrom
influenzae (beta-lactamase
(beta-lactamase negative)
susceptible at
lactamase negative) and H. influenzae
negative) are considered susceptible
NMT 1 mcg/ml
mcg/ml and resistant
resistant at NLT 4 mcg/ml;
mcg/ml; Str. pneumoniae
pneumoniae are considered susceptible
susceptible to
amoxicillin at MIC NMT 2 mcg/ml and resistant at NLT 8 mcg/ml.
Susceptibility data
Strains of the
the following
following named
named organisms
organisms are generally
generally sensitive
bactericidal action
action of
Strains
sensitive to
to the bactericidal
amoxicillin in vitro.
Susceptible Gram-positive
Gram-positive aerobes
aerobes include:
include: Enterococcus
Enterococcus faecalis
faecalis (Note
(Note 2),
2), Streptococcus
Susceptible
pneumoniae (Notes 1, 3), Streptococcus pyogenes (Notes 1, 3), Streptococcus viridans (Note 2),
Page 10 of 13
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APOTEX NZ LTD
APO-AMOXI
equivalent to
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Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin trihydrate
trihydrate equivalent
Streptococcus agalactiae,
agalactiae, Streptococcus
Streptococcus bovis,
bovis, Staphylococcus
Staphylococcus aureus
aureus (penicillin
(penicillin sensitive),
sensitive),
Streptococcus
Corynebacterium species (Note 2), Bacillus anthracis, Listeria monocytogenes.
Susceptible Gram-negative
Gram-negative aerobes
aerobes include:
include: Haemophilus
Haemophilus influenzae
influenzae (Note
(Note 3), Haemophilus
Susceptible
parainfluenzae (Note 3), Escherichia coli (Note 3), Proteus mirabilis, Salmonella species (Note 2),
Shigella species (Note 2), Bordetella pertussis, Brucella species (Note 1), Neisseria gonorrhoeae
(Note 2), Neisseria meningitidis (Note 1), Pasteurella septica, Helicobacter pylori, Leptospira spp,
Vibrio Cholerae
Susceptible anaerobes
anaerobes include:
include: Bacteroides melaninogenicus
melaninogenicus (Note
(Note 2), Clostridium species,
Susceptible
Fusobacterium spp. (Note 2), Peptostreptococci
Other susceptible organisms include Borrelia burgdorferi.
Note 1: No beta-lactamase producers have as yet been reported for these bacterial species. Note
2: Inconstantly
Inconstantly susceptible;
susceptible; susceptibility
absence of
2:
susceptibilityisis therefore
therefore unpredictable
unpredictableinin the
the absence
susceptibility testing.
susceptibility
testing. Note
Note 3: Clinical efficacy has been demonstrated for susceptible isolates in
approved clinical indications.
Resistance
Bacteria may be resistant
resistant to amoxicillin
amoxicillin due
due to
to production
production of
of beta-lactamases
beta-lactamases which
which hydrolyse
hydrolyse
Bacteria
aminopenicillins, due to alteration in penicillin-binding proteins, due to impermeability to the drug,
due to
to drug
drug efflux
efflux pumps.
pumps. One
One or
or more
more of
of these
these mechanisms
mechanisms may co-exist
co-exist in the
the same
same
or due
organism, leading
unpredictable cross-resistance
cross-resistance to other beta-lactams
beta-lactams and to
organism,
leading to a variable and unpredictable
antibacterial drugs of other classes.
Resistant Gram-positive aerobes include: Staphylococcus (beta-lactamase producing strains).
Resistant Gram-negative
Gram-negative aerobes include:
include: Acinetobacter spp., Citrobacter spp., Enterobacter
Resistant
Moraxella catarrhalis
catarrhalis (non-susceptible
(non-susceptible isolates),
isolates), Proteus spp.
spp. (indole
(indole
spp., Klebsiella spp., Moraxella
positive), Proteus vulgaris, Providencia spp., Pseudomonas spp., Serratia spp.
Resistant anaerobes include: Bacteroides fragilis.
Other resistant organisms include: Chlamydia, Mycoplasma, Rickettsia
Pharmacokinetics
Absorption
Amoxicillin is stable in the presence of gastric acid and rapidly absorbed from the gut to an extent
to 93%.
93%. Absorption
Absorption is independent
independent of food intake.
intake. Peak
of 72 to
Peak blood
blood levels
levels are
are achieved
achieved 11 to 2
hours after
after administration.
administration. After
500 mg doses
doses of
of amoxicillin,
amoxicillin, average
average peak
peak serum
serum
hours
After 250
250 and
and 500
concentrations of 5.2 mcg/ml and 8.3 mcg/ml respectively have been reported.
Distribution
Amoxicillin is not highly protein bound. Approximately 18% of total plasma drug content is bound
to protein.
protein. Amoxicillin
Amoxicillin diffuses
tissues and fluids,
fluids, including
including sputum and
diffuses readily
readily into
into most body tissues
brain and
and spinal
spinal fluid.
fluid. Inflammation
Inflammation generally increases the permeability of the
saliva but not the brain
meninges to penicillins and this may apply to amoxicillin. Amoxicillin diffuses across the placenta
and a small percentage is excreted into the breast milk.
Biotransformation
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A
APOTEX NZ LTD
APO-AMOXI
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin trihydrate
trihydrate equivalent
Amoxicillin is
where itit exists
exists in
in aahigh
highconcentration.
concentration. Amoxicillin
Amoxicillin is
Amoxicillin
is excreted
excreted mainly
mainly via the urine where
partly excreted
urine as the
the inactive
inactive penicilloic
penicilloic acid
quantities equivalent
also partly
excreted in
in the urine
acid in quantities
equivalent to
to 10 to
25% of
of the
the initial
initial dose.
dose. Small
Small amounts
amounts of
the drug
drug are
are also
also excreted
excreted in
in faeces
faeces and
and bile.
bile.
25%
of the
Concentrations in the bile may vary and are
are dependent
dependentupon
upon normal
normalbiliary
biliary function.
function.
Elimination
Approximately 60
70% of
of amoxicillin
amoxicillin is excreted
excreted unchanged
unchanged in urine
urine during
during the first
first 6 hours
hours
Approximately
60 to
to 70%
after administration
administration ofof aa standard
standard dose.
elimination half
life is
is approximately
approximately 1 hour.
hour.
after
dose. The elimination
half life
Concurrent
Concurrent administration
administration of
of probenecid
probenecid delays
delays amoxicillin
amoxicillin excretion.
excretion. In
In patients
patients with
with end-stage
substance is haemodialysable
renal failure, the half-life
half-life ranges
ranges between 5 to 20 hours. The substance
Chemical Structure
H
N
\
,
o
List of excipients
Each capsule
capsule contains
contains the
the following
following excipients:
Each
Croscarmellose sodium, Silicon dioxide,
dioxide, Stearic acid and gelatin capsule shell.
The capsule
capsule shell
shell also
also contains
contains the
the following
following colourants:
colourants:
Bluish and Titanium dioxide.
Allura red, Brilliant Blue, Quinoline yellow, Sunset yellow, Eosine I Bluish
Pharmaceutical Precautions
Shelf-Life
Shelf life: 3 years from the date of manufacture.
Special Precautions for Storage
°C
Store at or below 25
25°C
Protect from heat light and moisture.
Package Quantities
APO-AMOXI 250 mg capsules: Bottles of 28, 100 and 500 capsules.
APO-AMOXI 500 mg capsules: Bottles of 28, 100 and 500 capsules
Not all strengths and packs sizes may be available.
Medicine Schedule
Prescription
Prescription Medicine
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themost
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recentdatasheet
datasheet Page
A
APOTEX NZ LTD
APO-AMOXI
equivalent to
toAmoxicillin
Amoxicillin 250mg
250mg and
and 500mg
500mgcapsules
capsules
Amoxicillin trihydrate
trihydrate equivalent
Sponsor Details
Apotex NZ Ltd
32 Hillside Road
Glenfield
Private Bag
Private
Bag 102-995
102-995
North Shore Mail Centre
Auckland
Telephone:
Telephone: (09) 444 2073
Fax:
Fax: (09)
(09) 444 2951
Date of Preparation
2016
15 April
April 2016
refer to Medsafe website
website (www.medsafe.govt.nz) for
datasheet
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datasheet Page