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CAPRILŪ
TABLETS
Antihypertensive
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COMPOSITION
AND ACTION
CAPRIL
tablets 12.5 mg :
Each tablet contains12.5 mg captopril. CAPRIL tablets 25 mg : Each
tablet contains25 mg captopril. CAPRIL tablets 50 mg : Each tablet
contains 50 mg captopril.
ACTION
Captopril, 1-[(2S)-3-mercapto-2-methyl-propionyl]-L-proline,
is a highly specific competitive inhibitor of angiotensin I-converting
enzyme, the enzyme responsible for the conversions of angiotensin
I to angiotensin II.
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INDICATIONS
Hypertension:
Mild to moderate hypertension as an adjunct to thiazide therapy
in patients who have not responded effectively to thiazide treatment
alone.
Severe hypertension where standard therapy has failed. Congestive
Heart Failure: CAPRIL is indicated for the treatment of severe,
treatment-refractory congestive heart failure.
The drug should be used together with diuretics and where appropriate
digitalis.
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CONTRAINDICATIONS,
PRECAUTIONS AND WARNINGS
Contraindications
:
1) A history of previous hypersensitivity to captopril.
2) Angioedema caused by any ACE inhibitors.
Pregnancy
:
Captopril has been shown to be lethal to rabbit and sheep foetuses
.There were no foeto toxic effects to hamster or rat foetuses .Capril
is contraincated in pregnancy and should not be used in women of
child bearing potential unless protected by effective contraception
.
Precautions
:
Evaluation of the hypertensive patient should include assessment
of renal function prior to initiation of therapy. Patients with
renal impairment should not normally be treated with captopril.
CAPRIL should not be used in patients with aortic stenosis or outflow
tract obstruction.
The incidence of adverse reactions of captopril
is principally associated with renal function since the drug is
excreted primarily by the kidney. The dose should not exceed that
necessary for adequate control and should be reduced in patients
with impaired renal function.
Haematological
: Neutropenia/Agranulocytosis, thrombocytopenia and anaemia
have been reported in patients receiving Captopril. In patients
with normal renal function and no other complicating factors, neutropenia
occurs rarely.
CAPRIL should not be used routinely in patients with pre-existing
impaired renal function, collagen vascular disease, immunosuppressant
therapy, treatment with allopurinol or procainamide, or a combination
of these complicating factors, because neutropenia has been limited
almost exclusively to this group.
Some of these patients developed serious infections which in a few
instances did not respond to intensive antibiotic therapy. If CAPRIL
is used in such patients, it is advised that white blood cells count
and differential counts should be performed prior to therapy, every
2 weeks during the first 3 months of CAPRIL therapy, and periodically
thereafter.
During treatment, all patients should be instructed to report any
sign of infection (e.g. sore throat, fever), when a differential
white blood cells count should be performed.
CAPRIL and other concomitant medication should be withdrawn if neutropenia
(neutrophils less than 1000/mm3 ), is detected or suspected. In
most patients neutrophil counts rapidly returned to normal upon
discontinuing CAPRIL.
Renal
: Proteinuria in patients with prior normal renal function
is rare. Where PROTEINURIA has occurred it has usually been in patients
with severe hypertension and evidence of prior renal disease. Nephrotic
syndrome occurred in some of these patients. In patients with evidence
of prior renal disease, monthly urinary protein estimations (dip
stick) are recommended for the first 9 months of therapy. If repeated
determinations show increasing amounts of urinary protein, a 24-hour
quantitative determination should be obtained, and if this exceeds
1 g/day, the benefits and risks of continuing CAPRIL should be evaluated.
Although membranous glomerulopathy was found in biopsies taken from
some proteinuric patients, a casual relationship to CAPRIL has not
been established. Some patients with renal disease, particularly
those with bilateral renal artery stenosis or unilateral renal artery
stenosis in a single functioning kidney, have developed increased
concentrations of blood urea and serum creatinine.
CAPRIL dosage reduction and/or discontinuation of diuretic may be
required. For some of these patients it may not be possible to normalize
blood pressure and maintain adequate renal perfusion.
Hypotension
: With the first one or two doses some patients may experience
symptomatic hypotension. In most instances, symptoms are relieved
simply by the patient lying down. In patients with severe and renin
dependent hypertension (e.g. renovascular hypertension) or severe
congestive heart failure who are receiving large doses of diuretic,
exaggerated hypotensive responses have occurred usually within one
hour of the initial dose of CAPRIL.
In these patients, by discontinuing diuretic therapy or significantly
reducing the diuretic dose for four to seven days prior to initiating
CAPRIL, the possibility of this occurrence is reduced. By initiating
CAPRIL therapy with small doses (6.25 mg or 12.5 mg) the duration
of any hypotensive effect is lessened. Some patients may benefit
from an infusion of saline. The occurrence of first dose hypotension
does not preclude subsequent dose titration with CAPRIL.
Serum
potassium : Since CAPRIL decreases aldosterone production,
serum potassium is usually maintained in patients on diuretics.
Potassium sparing diuretics or potassium supplements should not
therefore be used routinely. In patients with marked renal impairment
a significant elevation of serum potassium may occur.
Nursing
Mothers : Because captopril is excreted in breast milk, CAPRIL
should not be used in nursing mothers.
Surgery
/ Anaesthesia : In patients undergoing major surgery, or
during anaesthesia with agents which produce hypotension, captopril
will block angiotensin II formation secondary to compensatory renin
release. This may lead to hypotension which can be corrected by
volume expansion.
Clinical
Chemistry : CAPRIL may cause a false-positive urine test
for acetone.
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SIDE
EFFECTS
Haematological
: Neutropenia, anaemia and thrombocytopenia (see Warnings).
Renal : Proteinuria, elevated blood urea and creatinine, elevated
serum potassium and acidosis (see Warnings).
Cardiovascular
: Hypotension (see Warnings) tachycardia.
Skin
: Rashes, usually pruritic, may occur. They are usually mild
transient and maculopapular, rarely urticarial. In a few cases the
rash has been associated with fever and some patients have developed
angio-neurotic oedema.
Pruritus, flushing, vesicular rash, and photosensitivity have been
reported.
Gastrointestinal
: Reversible and usually self-limiting taste impairment has
been reported.
Weight loss may be associated with the loss of taste. Stomatitis,
resembling aphthous ulcers, has been reported. Elevation of liver
enzymes has been noted in a few patients. Rare cases of hepatocellular
injury and cholestatic jaundice have been reported. Gastric irritation
and abdominal pain may occur.
Other
: Paraesthesia of the hands, serum sickness, cough, bronchospasm
and lymphadenopathy have been reported.
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OVERDOSAGE
In
the event of overdosage, blood pressure should be monitored and
if hypotension develops volume expansion is the treatment of choice.
Captopril is removed by dialysis.
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DRUG
INTERACTIONS
Diuretics
: Diuretics potentiate the anti-hypertensive effectiveness
of CAPRIL.
Potassium-sparing diuretics (triamterene, amiloride and spironolactone),
or potassium supplements may cause significant increase in serum
potassium.
Indomethacin
: A reduction of anti-hypertensive effectiveness may occur.
This is probably also the case with other non-steroidal anti-inflammatory
drugs.
Vasodilators : Captopril has been reported
to act synergistically with peripheral vasodilators such as minoxidil.
Awareness of this interaction may avert an initial hypotensive response.
Clonidine : It has been suggested that
the anti-hypertensive effect of CAPRIL can be delayed when patients
treated with clonidine are changed to CAPRIL.
Allopurinol
& Procainamide: reports of neutropoenia
&/or Steven Jhonson Syndrome have been documented in patients
using CAPRIL concurrenlty with either medication although, a casual
relationship has not been established. It is prudent to use this
combination with caution especially in renally impaired patients.
Immunosuppressants:
Azathioprine and cyclophosphamide have been associated with blood
dyscrasias in patients with renal failure who were also taking CAPRIL.
Probenecid:
The renal clearance of CAPRIL is reduced in the presence
of probenecid.
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RECOMMENDED
DOSE AND DOSAGE SCHEDULE
Hypertension
: Treatment with CAPRIL should be started
at the lowest effective dose which should be titrated according
to the needs of the patient.
In severe hypertension the starting dose is 12.5 mg b.d. The dosage
may be increased incrementally to a maximum of 50 mg t.i.d. CAPRIL
should be used together with other anti-hypertensive agents but
the dose of these should be individually titrated.
A daily dose of 150 mg of CAPRIL should not normally be exceeded.
Heart Failure : CAPRIL therapy must
be started under close medical supervision.
The usual dose is 25 mg three times a day. A starting dose of 6.25
mg or 12.5 mg may minimize a transient hypotensive effect, the usual
maximum dose is 150 mg daily. Increases in dosage should be delayed
for at least two weeks to determine if a satisfactory response has
occurred.
CAPRIL should be used in conjunction with a diuretic and where appropriate
digitalis.
Elderly : The dose should be titrated
against the blood pressure and kept as low as possible to achieve
adequate control. Since elderly patients may have reduced renal
function and other organ dysfunction, it is suggested that a low
dose of captopril be used initially.
Children : Captopril is not recommended
for the treatment of mild to moderate hypertension in children.
Safety and effectiveness in children have not been established.
Experience in neonates and premature infants is limited.
The starting dose should be 0.3 mg per Kg bodyweight up to a maximum
of 6 mg per Kg bodyweight in divided daily doses. The dose should
be individualized according to the response and may be given two
or three times daily.
Patients with renal impairment : CAPRIL
is not recommended in patients with renal impairment. Where it is
clinically indicated in severely hypertensive patients with impaired
renal function, the dose should be kept as low as possible to maintain
adequate blood pressure control. The dose can be titrated against
the response but adequate time should be allowed between dosage
adjustments. In these patients a loop-diuretic rather than a thiazide
should be the diuretic of choice.
CAPRIL is readily eliminated by haemodialysis.
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PRESENTATIONS
AND STORAGE
CAPRIL tablets
12.5mg, 25mg and 50mg are available in Blisters.
Storage : Store below 30°C .Union
of Arab Pharmacists
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