page169
Hepatic impairment
manufacturer advises caution in
cirrhotic patients with moderate hepatic impairment;
avoid in liver disease with coagulopathy
Renal impairment
use with caution if eGFR 15–
29 mL/minute/1.73 m
2
or if eGFR 30–49 mL/min-
ute/1.73 m
2
and concomitant use of drugs that
increase plasma-rivaroxaban concentration (consult
product literature);
avoid if eGFR less than 15 mL/
minute/1.73 m
2
Pregnancy
manufacturer advises avoid—toxicity in
animal
studies
Breast-feeding
manufacturer advises avoid—present
in milk in
animal
studies
Side-effects
nausea;
haemorrhage (see notes above);
less commonly
constipation,
diarrhoea,
dyspepsia,
dry mouth,
vomiting,
hypotension,
oedema,
tachy-
cardia, thrombocythaemia,
syncope,
dizziness,
head-
ache,
renal impairment,
pain in extremities,
pruritus,
and rash;
jaundice also reported
Dose
. Prophylaxis of venous thromboembolism following
knee replacement surgery,
ADULT
over 18 years, 10 mg
once daily for 2 weeks starting 6–10 hours after
surgery
. Prophylaxis of venous thromboembolism following
hip replacement surgery,
ADULT
over 18 years, 10 mg
once daily for 5 weeks starting 6–10 hours after
surgery
Xarelto
c
(Bayer Schering) T A
Tablets
, red, f/c, rivaroxaban 10 mg, net price 10-tab
pack = £44.15, 30-tab pack = £132.44, 100-tab pack =
£441.45
2.8.3
Protamine sulphate
Protamine sulphate is
used to treat
overdosage of
unfractionated or
low molecular
weight
heparin.
The
long half-life of
low molecular weight heparins should
be taken into consideration when determining the dose
of
protamine sulphate;
the effects
of
low molecular
weight
heparins can persist
for
up to 24 hours after
administration.
Excessive doses of
protamine sulphate
can have an anticoagulant effect.
PROTAMINE SULPHATE
(Protamine Sulfate)
Indications
see above
Cautions
see above; also monitor activated partial
thromboplastin time or other appropriate blood clot-
ting parameters;
increased risk of allergic reaction to
protamine (including previous treatment with prot-
amine or protamine insulin, allergy to fish,
men who
are infertile or who have had a vasectomy)
Side-effects
nausea,
vomiting,
lassitude,
flushing,
hypotension,
hypertension, bradycardia, dyspnoea,
rebound bleeding,
back pain;
hypersensitivity reac-
tions (including angioedema,
anaphylaxis) and pulm-
onary oedema reported
Dose
. Overdosage with intravenous injection of unfractio-
nated heparin,
by intravenous injection (rate not
exceeding 5 mg/minute),
1 mg neutralises 80–
100 units heparin when given within 15 minutes of
heparin;
if longer than 15 minutes since heparin,
less
protamine required (consult product literature for
details) as heparin rapidly excreted;
max. 50 mg
. Overdosage with intravenous infusion of unfractio-
nated heparin,
by intravenous injection (rate not
exceeding 5 mg/minute),
25–50 mg once heparin
infusion stopped
. Overdosage with subcutaneous injection of unfrac-
tionated heparin,
1 mg neutralises 100 units heparin;
give 25–50 mg
by intravenous injection (rate not
exceeding 5 mg/minute) then any remaining dose
given by intravenous infusion over 8–16 hours;
max.
total dose 50 mg
. Overdosage with subcutaneous injection of low
molecular weight heparin,
by intermittent intravenous
injection (rate not exceeding 5 mg/minute) or by
continuous intravenous infusion,
1 mg neutralises
approx.
100 units low molecular weight heparin
(consult product literature of low molecular weight
heparin for details);
max.
50 mg
Protamine Sulphate
(Non-proprietary) A
Injection
, protamine sulphate 10 mg /mL, net price 5-
mL amp = £1.43,
10-mL amp = £4.15
2.9
Antiplatelet drugs
Antiplatelet
drugs
decrease platelet
aggregation and
inhibit
thrombus formation in the arterial
circulation,
because in faster-flowing vessels,
thrombi
are com-
posed mainly of platelets with little fibrin.
Use of aspirin in primary prevention of cardiovascular
events, in patients with or without diabetes, is of unpro-
ven benefit. Long-term use of aspirin, in a dose of 75 mg
daily,
is of benefit in established cardiovascular disease
(secondary prevention);
unduly high blood pressure
must be controlled before aspirin is given. If the patient
is at a high risk of
gastro-intestinal
bleeding,
a proton
pump inhibitor (section 1.3.5) can be added.
Aspirin in a dose of 75–300 mg daily is given following
coronary bypass
surgery.
For
details
on the use of
aspirin in atrial
fibrillation see section 2.3.1;
for inter-
mittent claudication see section 2.6.4; for stable angina
and acute coronary syndromes see section 2.10.1;
for
use following placement of coronary stents see below;
for use in stroke see also below.
Clopidogrel is licensed for the prevention of ischaemic
events
in
patients
with
a
history
of
symptomatic
ischaemic disease.
Clopidogrel,
in combination with
low-dose aspirin,
is also licensed for
acute coronary
syndrome
without
ST-segment
elevation
(section
2.10.1);
in these
circumstances
the
combination is
given for up to 12 months (most benefit occurs during
the first
3 months;
there is
no evidence of
benefit
beyond 12 months).
Clopidogrel,
in combination with
low-dose aspirin,
is also licensed for acute myocardial
infarction with ST-segment
elevation (section 2.10.1);
the combination is licensed for at least 4 weeks, but the
optimum treatment duration has not been established.
In patients undergoing percutaneous coronary interven-
tion, clopidogrel is used as an adjunct with aspirin (see
also below). Patients,
who are not already taking clopi-
dogrel,
should receive a 300 mg loading dose prior to
the procedure; alternatively, a 600 mg [unlicensed] load-
ing dose may produce a greater and more rapid inhibi-
tion of
platelet
aggregation.
Use of
clopidogrel
with
aspirin increases the risk of bleeding. Clopidogrel mono-
therapy is an alternative when aspirin is contra-indi-
BNF 61
2.8.3 Protamine sulphate
149
2
Cardiovascular system