page164
Renal impairment
caution in moderate impairment;
increased risk of bleeding (monitor anti-Factor Xa
activity);
avoid in severe impairment unless patient
has heparin-induced thrombocytopenia and no alter-
native available
Pregnancy
manufacturer advises avoid—limited
information available but not known to be harmful
Breast-feeding
amount probably too small to be
harmful but manufacturer advises avoid
Side-effects
bleeding;
hypersensitivity reactions
(including rash)
Dose
. Prevention of deep-vein thrombosis, by subcuta-
neous injection,
750 units twice daily for 7–10 days;
initiate treatment before operation (with last pre-
operative dose 1–4 hours before surgery)
. Thromboembolic disease in patients with history of
heparin-induced thrombocytopenia,
by intravenous
injection,
2500 units (1250 units if body-weight under
55 kg,
3750 units if over 90 kg),
followed by intra-
venous infusion of 400 units/hour for 2 hours,
then
300 units/hour for 2 hours,
then
200 units/hour for 5
days
Orgaran
c
(Organon) A
Injection
,
danaparoid sodium 1250 units/mL, net
price 0.6-mL amp (750 units) = £26.68
Hirudins
Lepirudin,
a recombinant hirudin,
is licensed for anti-
coagulation in patients with Type II (immune) heparin-
induced thrombocytopenia who require parenteral anti-
thrombotic treatment. The dose of lepirudin is adjusted
according
to
activated
partial
thromboplastin
time
(APTT).
Bivalirudin,
a hirudin analogue,
is a thrombin
inhibitor
which is
licensed for
acute coronary syn-
dromes in patients planned for urgent or early interven-
tion,
and as an anticoagulant
for patients undergoing
percutaneous coronary intervention (see also section
2.10.1); bivalirudin should be administered in combina-
tion with aspirin and clopidogrel.
The
Scottish Medi-
cines Consortium
(p.
4)
has advised (November 2008)
that bivalirudin (
Angiox
c
) is accepted for restricted use
within NHS Scotland for patients with acute coronary
syndromes planned for urgent or early intervention who
would
have
been
considered
for
treatment
with
unfractionated heparin in combination with a glycopro-
tein IIb/IIIa inhibitor;
it
should not
be used as
an
alternative to heparin alone.
The
Scottish Medicines
Consortium
(p.
4)
has
advised
(August
2010)
that
bivalirudin (
Angiox
c
)
is
accepted for
restricted use
within NHS Scotland as an anticoagulant
in patients
undergoing percutaneous
coronary intervention who
would
have
been
considered
for
treatment
with
unfractionated heparin in combination with a glycopro-
tein IIb/IIIa inhibitor;
it
should not
be used as
an
alternative to heparin alone.
BIVALIRUDIN
Indications
acute coronary syndromes in patients
planned for urgent or early intervention;
anti-
coagulation for patients undergoing percutaneous
coronary intervention (PCI)
Cautions
exposure to lepirudin (theoretical risk from
lepirudin antibodies);
brachytherapy procedures;
concomitant use of drugs that increase risk of bleed-
ing
Contra-indications
severe hypertension;
subacute
bacterial endocarditis;
active bleeding;
bleeding dis-
orders
Renal impairment
for
percutaneous coronary inter-
vention
,
reduce rate of infusion to 1.4 mg/kg/hour if
eGFR 30–60 mL/minute/1.73 m
2
and monitor blood
clotting parameters;
for
acute coronary syndromes
and
percutaneous coronary intervention
,
avoid if
eGFR less than 30 mL/minute/1.73 m
2
Pregnancy
manufacturer advises avoid unless poten-
tial benefit outweighs risk—no information available
Breast-feeding
manufacturer advises caution—no
information available
Side-effects
bleeding (discontinue), thrombosis,
ecchymosis;
less commonly
nausea,
vomiting, tachy-
cardia, bradycardia, hypotension,
angina,
dyspnoea,
allergic reactions (including isolated reports of
anaphylaxis),
headache,
thrombocytopenia,
anaemia,
back and chest pain, and injection-site reactions
Dose
. Acute coronary syndromes (in addition to aspirin and
clopidogrel),
initially by intravenous injection,
100 micrograms/kg then by intravenous infusion
250 micrograms/kg/hour (for up to 72 hours in
medically managed patients);
patients proceeding to
percutaneous coronary intervention or coronary
artery bypass surgery
without
cardiopulmonary
bypass, additional bolus dose by intravenous injection
500 micrograms/kg,
then by intravenous infusion
1.75 mg/kg/hour for duration of procedure; following
percutaneous coronary intervention,
reduce infusion
rate to 250 micrograms/kg/hour for 4–12 hours as
necessary;
patients proceeding to coronary artery
bypass surgery
with
cardiopulmonary bypass,
dis-
continue intravenous infusion 1 hour before proce-
dure and treat with unfractionated heparin
. Anticoagulation in patients undergoing percutaneous
coronary intervention (in addition to aspirin and clo-
pidogrel),
initially
by intravenous injection,
750 micr-
ograms/kg then
by intravenous infusion 1.75 mg/kg/
hour for up to 4 hours after procedure;
a reduced
infusion rate of 250 micrograms/kg/hour may be
continued for a further 4–12 hours if necessary
Angiox
c
(The Medicines Company) T A
Injection
,
powder for reconstitution,
bivalirudin,
net
price 250-mg vial = £310.00
LEPIRUDIN
Indications
thromboembolic disease requiring par-
enteral anticoagulation in patients with heparin-
induced thrombocytopenia type II
Cautions
recent bleeding or risk of bleeding including
recent puncture of large vessels, organ biopsy, recent
major surgery,
stroke,
bleeding disorders, severe
hypertension, bacterial endocarditis; concomitant use
of drugs that increase risk of bleeding;
determine
activated partial thromboplastin time 4 hours after
start of treatment (or after infusion rate altered) and at
least once daily thereafter
Hepatic impairment
no information—manufacturer
advises that cirrhosis may affect renal excretion
Renal impairment
reduce initial intravenous injection
dose to 200 micrograms/kg and reduce subsequent
infusion dose by 50–85% if eGFR less than 60 mL/
144
2.8.1 Parenteral anticoagulants
BNF 61
2
Cardiovascular system