page136
patients known to have these forms of critical renovas-
cular disease.
ACE inhibitor treatment is unlikely to have an adverse
effect on overall
renal
function in patients with severe
unilateral
renal
artery stenosis and a normal
contralat-
eral
kidney,
but
glomerular
filtration is
likely to be
reduced (or even abolished) in the affected kidney and
the long-term consequences are unknown.
ACE inhibitors are therefore best
avoided in patients
with known or suspected renovascular disease,
unless
the blood pressure cannot be controlled by other drugs.
If ACE inhibitors are used, they should be initiated only
under specialist supervision and renal
function should
be monitored regularly.
ACE inhibitors
should also be used with particular
caution in patients who may have undiagnosed and
clinically
silent
renovascular
disease.
This
includes
patients with peripheral
vascular disease or those with
severe generalised atherosclerosis.
Cautions
ACE inhibitors need to be initiated with care
in patients receiving diuretics (important:
see Conco-
mitant
diuretics,
below);
first
doses can cause hypo-
tension especially in patients taking high doses of diur-
etics,
on a low-sodium diet,
on dialysis,
dehydrated,
or
with heart failure (see above). They should also be used
with caution in peripheral
vascular disease or general-
ised atherosclerosis
owing to risk of
clinically silent
renovascular disease; for use in pre-existing renovascu-
lar
disease,
see
Renal
Effects
above.
The
risk
of
agranulocytosis is possibly increased in collagen vascu-
lar
disease (blood counts
recommended).
ACE inhi-
bitors should be used with care in patients with severe
or symptomatic aortic stenosis (risk of hypotension) and
in hypertrophic cardiomyopathy.
They should also be
used with care (or avoided) in those with a history of
idiopathic or
hereditary angioedema.
If
jaundice or
marked elevations of
hepatic enzymes
occur
during
treatment then the ACE inhibitor should be discontin-
ued—risk of hepatic necrosis (see also Hepatic impair-
ment,
below).
Interactions:
Appendix 1 (ACE inhi-
bitors).
Anaphylactoid
reactions
To
prevent
anaphylactoid
reactions,
ACE inhibitors
should be avoided during
dialysis
with
high-flux
polyacrylonitrile
membranes
and
during
low-density
lipoprotein
apheresis
with
dextran sulphate;
they should also be withheld before
desensitisation with wasp or bee venom.
Concomitant diuretics
ACE inhibitors can cause a very
rapid fall in blood pressure in volume-depleted patients;
treatment
should therefore be initiated with very low
doses.
If
the dose of
diuretic is
greater
than 80 mg
furosemide or equivalent,
the ACE inhibitor should be
initiated under close supervision and in some patients
the diuretic dose may need to be reduced or the diuretic
discontinued at least 24 hours beforehand (may not be
possible in heart failure—risk of pulmonary oedema). If
high-dose diuretic therapy cannot
be stopped,
close
observation is
recommended after
administration of
the first dose of
ACE inhibitor,
for at least 2 hours or
until the blood pressure has stabilised.
Contra-indications
ACE inhibitors are contra-indi-
cated in patients with hypersensitivity to ACE inhibitors
(including angioedema).
Hepatic impairment
Use of prodrugs such as cilaza-
pril,
enalapril,
fosinopril,
imidapril,
moexipril,
perindo-
pril,
quinapril,
ramipril,
and trandolapril
requires close
monitoring in patients with impaired liver function
Renal
impairment
ACE inhibitors should be used
with caution and the response monitored (see Renal
effects above);
hyperkalaemia and other
side effects
more common;
the dose may need to be reduced,
see
individual drugs.
Pregnancy
ACE inhibitors
should be
avoided in
pregnancy unless essential.
They may adversely affect
fetal
and neonatal
blood pressure control
and renal
function;
skull
defects and oligohydramnios have also
been reported.
Breast-feeding
Information on the use of ACE inhi-
bitors in breast-feeding is limited.
Cilazapril,
fosinopril,
imidapril, lisinopril, moexipril, perindopril, ramipril, and
trandolapril
are not
recommended;
alternative treat-
ment options, with better established safety information
during breast-feeding, are available. Captopril, enalapril,
and quinapril
should be avoided in the first few weeks
after delivery, particularly in preterm infants, due to the
risk of profound neonatal hypotension; if essential, they
may be used in mothers breast-feeding older infants—
the infant’s blood pressure should be monitored.
Side-effects
ACE inhibitors can cause profound hypo-
tension (see Cautions) and renal impairment (see Renal
effects above),
and a persistent
dry cough.
They can
also cause angioedema (onset may be delayed;
higher
incidence reported in Afro-Caribbean patients),
rash
(which may be associated with pruritus and urticaria),
pancreatitis, and upper respiratory-tract symptoms such
as sinusitis,
rhinitis,
and sore throat.
Gastro-intestinal
effects reported with ACE inhibitors include nausea,
vomiting, dyspepsia, diarrhoea, constipation, and abdo-
minal pain. Altered liver function tests, cholestatic jaun-
dice,
hepatitis,
fulminant hepatic necrosis,
and hepatic
failure have been reported—discontinue if marked ele-
vation of hepatic enzymes or jaundice.
Hyperkalaemia,
hypoglycaemia, and blood disorders including thrombo-
cytopenia,
leucopenia,
neutropenia,
and haemolytic
anaemia
have
also been reported.
Other
reported
side-effects
include
headache,
dizziness,
fatigue,
malaise, taste disturbance, paraesthesia, bronchospasm,
fever,
serositis,
vasculitis,
myalgia,
arthralgia,
positive
antinuclear antibody,
raised erythrocyte sedimentation
rate,
eosinophilia,
leucocytosis,
and photosensitivity.
Combination products
Products incorporating an
ACE inhibitor
with a thiazide diuretic or
a calcium-
channel
blocker are available for the management
of
hypertension. Use of these combination products should
be reserved for patients whose blood pressure has not
responded adequately to a single antihypertensive drug
and who have been stabilised on the individual compo-
nents of the combination in the same proportions.
CAPTOPRIL
Indications
mild to moderate essential hypertension
alone or with thiazide therapy and severe hyper-
tension resistant to other treatment; congestive heart
failure with left ventricular dysfunction (adjunct—see
section 2.5.5);
following myocardial infarction,
see
116
2.5.5 Drugs affecting the renin-angiotensin system
BNF 61
2
Cardiovascular system