Canada - English - Health Canada

Buy It Now

Active ingredient:
Available from:
ATC code:
INN (International Name):
Pharmaceutical form:
Administration route:
Units in package:
Prescription type:
Therapeutic area:
Product summary:
Active ingredient group (AIG) number: 0114954003; AHFS: 24:32.04
Authorization status:
Authorization number:
Authorization date:




Captopril Tablets USP

12.5, 25, 50 and 100 mg

Angiotensin-Converting Enzyme Inhibitor

Pro Doc Ltée


2925, boul. Industriel

March 7, 2008

Laval, Québec

H7L 3W9

Control number : 111881



Captopril Tablets USP

12.5, 25, 50 and 100 mg


Angiotensin-Converting Enzyme Inhibitor


Captopril is an angiotensin converting enzyme inhibitor which is used in the treatment of

hypertension and heart failure.

The mechanism of action of captopril has not yet been fully elucidated. It appears to lower blood

pressure and be an adjunct in the therapy of congestive heart failure primarily through

suppression of the renin-angiotensin-aldosterone system; however, there is no consistent

correlation between renin levels and response to the drug. Renin, an enzyme synthesized by the

kidneys, is released into the circulation where it acts on a plasma globulin substrate to produce

angiotensin I, a relatively inactive decapeptide. Angiotensin I is then converted by angiotensin-

converting enzyme (ACE) to angiotensin II, a potent endogenous vasoconstrictor substance.

Angiotensin II also stimulates aldosterone secretion from the adrenal cortex, thereby contributing

to sodium and fluid retention.

Captopril prevents the conversion of angiotensin I to angiotensin II by inhibition of ACE, a

peptidyldipeptide carboxy hydrolase.

ACE is identical to ‘bradykininase’, and captopril may also interfere with the degradation of the

vasodepressor peptide, bradykinin. However, the effectiveness of captopril in therapeutic doses

appears to be unrelated to potentiation of the actions of bradykinin. Increased concentrations of

bradykinin or prostaglandin E

may also have a role in the therapeutic effect of captopril,

especially in low-renin hypertension.

Inhibition of ACE results in decreased plasma angiotensin II and increased plasma renin activity

(PRA), the latter resulting from loss of negative feedback on renin release caused by reduction in

angiotensin II. The reduction of angiotensin II leads to decreased aldosterone secretion, and, as

a result, small increases in serum potassium may occur along with sodium and fluid loss.

The antihypertensive effects persist for a longer period of time than does demonstrable inhibition

of circulating ACE. It is not known whether the ACE present in vascular endothelium is inhibited

longer than the ACE in circulating blood.

Administration of captopril results in a reduction of peripheral arterial resistance in hypertensive

patients with either no change, or an increase, in cardiac output. There is an increase in renal

blood flow following administration of captopril and glomerular filtration rate is usually unchanged.

In instances of rapid reduction of long-standing or severely elevated blood pressure, the

glomerular filtration rate may decrease transiently.

Peak reductions of blood pressure usually occur within 60 to 90 minutes after oral administration

of a single dose of captopril. The duration of effect appears to be dose related. The reduction in

blood pressure may be progressive, so to achieve maximal therapeutic effects, several weeks of

therapy may be required. The blood pressure lowering effects of captopril and thiazide-type

diuretics appear to be additive. In contrast, captopril and beta-blockers have a less than additive


Blood pressure is lowered to about the same extent in both standing and supine positions.

Orthostatic effects and tachycardia are infrequent, but may occur in volume-depleted patients.

Abrupt withdrawal of captopril has not been associated with a rapid increase in blood pressure.

The antihypertensive effect of angiotensin-converting enzyme inhibitors is generally lower in black

patients than in non-blacks.

In patients with heart failure, captopril significantly decreased systemic vascular resistance

(afterload), reduced pulmonary capillary wedge pressure (preload) and pulmonary vascular

resistance, increased cardiac output (stroke index), and increased exercise tolerance time (ETT).

Clinical improvement has been observed in some patients where acute hemodynamic effects

were minimal.

Captopril has been studied in patients with diabetic nephropathy, most of whom had

hypertension, with type I insulin-dependent diabetes mellitus, retinopathy and proteinuria ≥ 500

mg/day, in a multicenter, double-blind, placebo-controlled trial. In this study, captopril has shown

to decrease the rate of progression of renal insufficiency and to reduce asssociated clinical

sequelae for the combined end-point of end- stage renal disease (dialysis or renal

transplantation) or death (from all causes). The effect on reduction of all-cause mortality alone

was not statistically significant. No dosage adjustment was made according to creatinine

clearance. Patients who had already progressed to severe renal failure were not included in the

clinical trial.

Studies in rats and cats indicate that captopril does not cross the blood-brain barrier to any

significant extent.


Following oral administration of therapeutic doses of captopril, rapid absorption occurs with peak

blood levels at about one hour. The presence of food in the gastrointestinal tract reduces

absorption by about 30 to 40%. Based on carbon-14 labeling, average minimal absorption is

approximately 70–75%. In a 24-hour period, over 95% of the absorbed dose is eliminated in the

urine; 40 to 50% is unchanged drug, although it appears this percentage may be smaller in

patients with congestive heart failure; most of the remainder is the disulfide dimer of captopril and

captopril-cysteine disulfide.

Approximately 25 to 30% of the circulating drug is bound to plasma proteins. The apparent

elimination half-life for total radioactivity in blood is about 4 hours. The half-life of unchanged

captopril is approximately 2 hours.

In patients with normal renal function, absorption and disposition of a labeled dose are not altered

after 7 days of captopril administration. In patients with renal impairment, however, retention of

captopril occurs (see DOSAGE AND ADMINISTRATION).

Comparative Bioavailability

Comparative bioavailability studies were performed using healthy human volunteers. The rate

and extent of absorption of captopril following administration of a single 100 mg (one 100 mg

tablet) dose of CAPTOPRIL or Capoten were measured and compared. Plasma concentration of

free captopril and serum concentration of total captopril were analyzed and recorded. The results

were summarized as follows:

Free Captopril



Percentage of


* (

1539 (37)

1438 (21)

* (

1282 (32)

1292 (25)



953 (35)

1056 (31)


0.9 (0.33)

0.8 (0.29)


0.9 (0.59)

0.7 (0.30)

Total Captopril



Percentage of


* (

11148 (39)

10754 (33)

* (

8791 (43)

8557 (36)



2898 (38)

2799 (31)


1.1 (0.43)

1.0 (0.32)


2.9 (1.5)

3.1 (2.0)

* Geometric means (CV)

** Arithmetic means (SD)



CAPTOPRIL (captopril) is indicated for the treatment of essential or renovascular hypertension. It

is usually administered in association with other drugs, particularly thiazide diuretics. The blood

pressure lowering effects of captopril and thiazides are approximately additive.

In using CAPTOPRIL, consideration should be given to the risk of neutropenia/agranulocytosis


In patients with normal renal function.

CAPTOPRIL should normally be used in those patients in whom treatment with diuretics

or beta-blockers was found ineffective or has been associated with unacceptable adverse


CAPTOPRIL can be tried as an initial agent in those patients with severe hypertension or

in those in whom the use of diuretics and/or beta-blockers is contraindicated or in patients

with medical conditions in which those drugs frequently cause serious adverse effects.

In patients with impaired renal function.

In these patients, particularly those with collagen vascular disease, captopril should be

reserved for hypertensives who have either developed unacceptable side effects on other

drugs, or have failed to respond satisfactorily to drug combinations (see WARNINGS).

Congestive Heart Failure:

CAPTOPRIL is indicated in the treatment of congestive heart failure as concomitant therapy with

a diuretic in patients who have not responded adequately to digitalis and diuretic or in whom the

administration of digitalis is contraindicated of has been associated with unacceptable side

effects. Captopril therapy must be initiated under close medical supervision.

Myocardial Infarction

CAPTOPRIL is indicated to improve survival, delay the onset of symptomatic heart failure and

reduce hospitalizations for heart failure following myocardial infarction in clinically stable patients

with left ventricular dysfunction manifested as an ejection fraction of ≤ 40%.

Diabetic Nephropathy

CAPTOPRIL is indicated for the treatment of diabetic nephropathy (proteinuria ≥500mg/day) in

patients with type

insulin-dependent diabetes mellitus and retinopathy.


CAPTOPRIL (captopril) is contraindicated in patients with a history of hypersensitivity to the drug

and in patients with a history of angioedema related to previous treatment with an Angiotensin

Converting Enzyme inhibitor.


Serious Warning

When used in pregnancy, angiotensin converting enzyme (ACE) inhibitors can cause

injury or even death of the developing fetus. When pregnancy is detected, CAPTOPRIL

should be discontinued as soon as possible.


Angioedema has been reported in patients treated with ACE inhibitors, including captopril.

Angioedema associated with laryngeal involvement may be fatal. If laryngeal stridor or

angioedema of the face, tongue, or glottis occurs, captopril should be discontinued immediately,

the patient treated appropriately in accordance with accepted medical care, and carefully

observed until the swelling disappears. In instances where swelling is confined to the face and

lips, the condition generally resolves without treatment, although antihistamines may be useful in

relieving symptoms. Where there is involvement of the tongue, glottis or larynx, likely to cause

airway obstruction, appropriate therapy (including but not limited to 0.3 to 0.5 mL of subcutaneous

epinephrine solution 1:1000) should be administered promptly (see ADVERSE REACTIONS).

The incidence of angioedema during ACE inhibitor therapy has been reported to be higher in

black than in non-black patients.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk

of angioedema while receiving an ACE inhibitor (see CONTRAINDICATIONS).


Total urinary proteins greater than 1 g per day were seen in less than one percent of patients

receiving captopril. These have been predominantly in those who had prior renal disease, or in

those receiving relatively high doses (in excess of 150 mg/day), or both. In patients without prior

evidence of renal disease, the incidence of proteinuria was 0.5%. In those patients without prior

evidence of renal disease receiving 150 mg of captopril or less per day, the incidence was 0.2%.

Parameters of renal function, such as BUN and serum creatinine were seldom altered in the

patients with proteinuria. In most cases, proteinuria subsided or cleared within 6 months whether

or not captopril was continued, but some patients had persistent proteinuria. Nephrotic syndrome

occurred in about one-fifth of the proteinuric patients.

Membranous glomerulopathy was found in biopsies taken from proteinuric patients. A causal

relationship to captopril has not been established since pre-treatment biopsies were not taken

and membranous glomerulopathy has been shown to occur in hypertensive patients not receiving


Since most cases of proteinuria occurred by the eighth month of therapy, patients with prior renal

disease or those receiving captopril at doses greater than 150 mg/day should have urinary

protein estimations (dip-stick on first morning urine, or quantitative 24-hour urine) prior to therapy,

at approximately monthly intervals for the first 9 months of treatment, and periodically thereafter.

When proteinuria is persistent, 24-hour quantitative determinations provide greater precision. For

patients who develop proteinuria exceeding 1 g/day, or proteinuria that is increasing, the benefits

and risks of continuing captopril should be evaluated.


Neutropenia, (<1000/mm

) with myeloid hypoplasia has resulted from use of captopril. About half

of the neutropenic patients developed systemic or oral cavity infections or other features of the

syndrome of agranulocytosis.

The risk of neutropenia is dependent on the clinical status of the patient:

In clinical trials in patients with hypertension who have normal renal function (serum

creatinine less than 1.6 mg/dL and no collagen disease), neutropenia has been seen in

one patient out of over 8600 exposed.

In patients with some degree of renal failure (serum creatinine at least 1.6 mg/dL) but no

collagen vascular disease, the risk of neutropenia in clinical trials was about 1 per 500, a

frequency over 15 times that for uncomplicated hypertension. Daily doses of captopril

were relatively high in these patients, particularly in view of their diminished renal function.

In patients with renal failure, use of allopurinol concomitantly with captopril has been

associated with neutropenia.

In patients with collagen vascular diseases (e.g., systemic lupus erythematosus,

scleroderma) and impaired renal function, neutropenia occurred in 3.7% of patients in

clinical trials.

While none of the over 750 patients in formal clinical trials of heart failure developed

neutropenia, it has occurred during the subsequent clinical experience. About half of the

reported cases had serum creatinine >1.6 mg/dL and more than 75% were in patients

also receiving procainamide. In heart failure, it appears that the same risk factors for

neutropenia are present.

The neutropenia has been detected within 3 months after captopril was started. Bone marrow

examinations in patients with neutropenia consistently showed myeloid hypoplasia, frequently

accompanied by erythroid hypoplasia and decreased numbers of megakaryocytes (e.g.,

hypoplastic bone marrow and pancytopenia); anemia and thrombocytopenia were sometimes


In general, neutrophils returned to normal in about two weeks after captopril was discontinued,

and serious infections were limited to clinically complex patients. About 13% of the cases of

neutropenia have ended fatally, but almost all fatalities were in patients with serious illness,

having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a

combination of these complicating factors.

Evaluation of the hypertensive or heart failure patient should always include assessment of renal


If captopril is used in patients with impaired renal function, white blood cell and differential counts

should be evaluated prior to starting treatment and at approximately two-week intervals for about

3 months, then periodically.

In patients with collagen vascular disease or who are exposed to other drugs known to affect the

white cells or immune response, particularly when there is impaired renal function, captopril

should be used only after an assessment of benefit and risk, and then with caution.

All patients treated with captopril should be told to report any signs of infection (e.g., sore throat,

fever). If infection is suspected, white cell counts should be performed without delay.

Since discontinuation of captopril and other drugs has generally led to prompt return of the white

cell count to normal, upon confirmation of neutropenia (neutrophil count <1000/mm

) the

physician should withdraw captopril and closely follow the patient’s course.

Since captopril decreases aldosterone production, elevation of serum potassium may occur

rarely, especially in patients with renal failure. (See PRECAUTIONS - Drug Interactions.)


Excessive hypotension was seen in hypertensive patients but is a possible consequence of

captopril use in severely salt/volume depleted persons such as those treated vigorously with

diuretics, for example patients with severe congestive heart failure (see PRECAUTIONS - Drug


In heart failure, where the blood pressure was either normal or low, decreases in mean blood

pressure greater than 20% were recorded in about half of the patients. This transient

hypotension may occur after any of the first several doses and produces either no symptoms or

brief mild lightheadedness, although in rare instances, it has been associated with arrhythmia or

conduction defects. Hypotension was the reason for discontinuation of drug in 3.6% of patients

with heart failure.



dose may minimize the hypotensive effect (see DOSAGE AND ADMINISTRATION). Patients

should be followed closely for the first two weeks of treatment and whenever the dose of

captopril, or diuretic, is increased. Similar considerations may apply to patients with ischemic

heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in

myocardial infarction or cerebrovascular accident.

Hypotension in itself is not a reason to discontinue captopril. If associated symptoms are

troublesome or persist, they are usually relieved by a reduction in the dose of either captopril or


Pregnant women

ACE inhibitors can cause fetal and neonatal morbidity and mortality when administered to

pregnant women. When pregnancy is detected, CAPTOPRIL (captopril) should be discontinued

as soon as possible.

The use of ACE inhibitors during the second and third trimesters of pregnancy has been

associated with fetal and neonatal injury including hypotension, neonatal skull hypoplasia, anuria,

reversible or irreversible renal failure, and death. Oligohydramnios has also been reported,

presumably resulting from decreased fetal renal function, associated with fetal limb contractures,

craniofacial deformation, and hypoplastic lung development.

Prematurity, patent ductus arteriosus, and other structural cardiac malformations, as well as

neurologic malformations, have also been reported following exposure in the first trimester of


Infants with a history of in utero exposure to ACE inhibitors should be closely observed for

hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward

support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required

as a means of reversing hypotension and/or substituting for impaired renal function, however,

limited experience with those procedures has not been associated with significant clinical benefit.

Captopril may be removed from the general circulation by hemodialysis.

Animal Data: Captopril was embryocidal in rabbits when given in doses 2 to 70 times (on a

mg/kg basis) the maximum recommended human dose, and low incidences of craniofacial

malformations were seen. These effects in rabbits were most probably due to the particularly

marked decrease in blood pressure caused by the drug in this species. Captopril was also

embryocidal in sheep when given in doses similar to those given in humans. Captopril given to

pregnant rats at 400 times the recommended human dose continuously during gestation and

lactation caused a reduction in neonatal survival.

No teratogenic effects have been observed after large doses of captopril were administered to

hamsters and rats.

Nursing women

The presence of concentrations of ACE inhibitor have been reported in human milk. Use of ACE

inhibitors is not recommended during breast-feeding.


Renal Impairment

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal

function have been seen in susceptible individuals. In patients whose renal function may depend

on the activity of the renin-angiotensin-aldosterone system, such as patients with bilateral renal

artery stenosis, unilateral renal artery stenosis to a solitary kidney, or severe congestive heart

failure, treatment with agents that inhibit this system has been associated with oliguria,

progressive azotemia, and rarely, acute renal failure and/or death. In susceptible patients,

concomitant diuretic use may further increase risk.

Use of CAPTOPRIL (captopril) should include appropriate assessment of renal function.


Elevation in serum potassium has been observed in some patients treated with ACE inhibitors,

including captopril. When treated with ACE inhibitors, patients at risk for the development of

hyperkalemia include those with: renal insufficiency, diabetes mellitus, and those using

concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt

substitutes, or other drugs associated with increases in serum potassium (eg. heparin).

The incidence of hyperkalemia related or possibly related to therapy in the diabetic patients

studied with nephropathy and proteinuria was 3.6% and was a reason for discontinuation of the

drug in 1% of the patients. Hyperkalemia was defined as persistent elevation of serum potassium

to 6.0 mg/dL or more in the absence of a remediable cause, such as other drugs, volume

depletion, exogenous potassium supplements, etc.

Impaired Liver Function

Elevation of liver enzymes and/or serum bilirubin, cases of cholestatic jaundice, and of

hepatocellular injury with or without secondary cholestasis, have occurred during therapy with

captopril in patients without pre-existing liver abnormalities. In most cases, the changes were

reversible on discontinuation of the drug. Should the patient receiving CAPTOPRIL experience

any unexplained symptoms (see Information for Patients), particularly during the first weeks or

months of treatment, it is recommended that a full set of liver enzyme tests and other necessary

investigations be carried out. Discontinuation of CAPTOPRIL should be considered when


There are no adequate studies in patients with cirrhosis and/or liver dysfunction. CAPTOPRIL

should be used with particular caution in patients with pre-existent liver abnormalities. Such

patients should have their baseline liver function test obtained before administration of the drug.

Close monitoring of response and metabolic effects should apply to these patients.


Cough has been reported with the use of CAPTOPRIL. Characteristically, ACE-inhibitor induced

cough is non-productive, persistent and resolves after discontinuation or lowering of the dose.

CAPTOPRIL induced cough should be considered as part of the differential diagnosis of the


Valvular Stenosis

There is concern, on theoretical grounds, that patients with aortic stenosis might be at particular

risk of decreased coronary perfusion when treated with vasodilators because they do not develop

as much afterload reduction.


In patients undergoing major surgery or during anesthesia with agents that 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.

Anaphylactoid Reactions During Membrane Exposure

Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes (eg.:

polyacrylonitrile [PAN]) and treated concomitantly with an ACE inhibitor. Dialysis should be

stopped immediately if symptoms such as nausea, abdominal cramps, burning, angioedema,

shortness of breath and severe hypotension occur. Symptoms are not relieved by antihistamines.

In these patients, considerations should be given to using a different type of dialysis membrane or

a different class of antihypertensive agents.

Anaphylactoid Reactions During Desensitization

There have been isolated reports of patients experiencing sustained life threatening

anaphylactoid reactions while receiving ACE inhibitors during desensitizing treatment with

hymenoptera (bees, wasps) venom. In the same patients, these reactions have been avoided

when ACE inhibitors were temporarily withheld for at least 24 hours, but they have reappeared

upon inadvertent rechallenge.

Pediatric Use

Safety and effectiveness in children have not been established although there is limited

experience with the use of captopril in children from 2 months to 15 years of age with secondary

hypertension and varying degrees of renal insufficiency. Dosage, on a weight basis, was

comparable to that used in adults. Captopril should be used in children only if other measures for

controlling blood pressure have not been effective.

Information for Patients

Patients should be told that taking CAPTOPRIL during pregnancy can cause injury and

even death to the developing fetus. Patients should be advised to stop taking the

medication and to contact their physician as soon as possible if they become pregnant

while taking CAPTOPRIL.

Patients should be advised that captopril may pass into breast milk and that they should not

breast-feed while taking CAPTOPRIL.

Patients should be told to report promptly any indication of infection (e.g., sore throat, fever),

which may be a sign of neutropenia, or of progressive edema, which might be related to

proteinuria and nephrotic syndrome.

All patients should be cautioned that excessive perspiration and dehydration may lead to an

excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume

depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should

be advised to consult with the physician.

Patients should be advised to return to the physician if he/she experiences any symptoms

possibly related to liver dysfunction. This would include viral like symptoms in the first weeks to

months of therapy (such as fever, malaise, muscle pain, rash or adenopathy which are possible

indicators of hypersensitivity reactions), or if abdominal pain, nausea or vomiting, loss of appetite,

jaundice, itching or any other unexplained symptoms occur during therapy.

Patients should be warned against interruption or discontinuation of antihypertensive medications

without the physician’s advice.

Patients treated for severe congestive heart failure should be cautioned to increase their physical

activity slowly.


Diuretic Therapy

: Patients on diuretics and especially those in whom diuretic therapy was

recently instituted, as well as those on severe dietary salt restriction or dialysis, may occasionally

experience a precipitous reduction of blood pressure usually within the first hour after receiving

the initial dose of captopril (see WARNINGS).

When feasible the hypotensive effects may be minimized by either discontinuing the diuretic or

increasing the salt intake approximately one week prior to initiation of treatment with captopril.

Alternatively, provide medical supervision for at least one hour after the initial dose. If

hypotension occurs, the patient should be placed in a supine position and, if necessary, receive

an intravenous infusion of normal saline. This transient hypotensive response is not a

contraindication to further doses which can be given without difficulty once the blood pressure

has increased after volume expansion.

Agents Having Vasodilator Activity

: Data on the effect of concomitant use of other vasodilators in

patients receiving captopril for heart failure are not available; therefore, nitroglycerin or other

nitrates (as used for management of angina) or other drugs having vasodilator activity should, if

possible, be discontinued before starting captopril. If resumed during captopril therapy, such

agents should be administered cautiously, and perhaps at a lower dosage.

Agents Causing Renin Release: Captopril’s effect will be augmented by antihypertensive agents

that cause renin release. For example, diuretics (e.g., thiazides) may activate the renin-

angiotensin-aldosterone system.

Agents Affecting Sympathetic Activity: The sympathetic nervous system may be especially

important in supporting blood pressure in patients receiving captopril alone or with diuretics.

Therefore, agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic

neuron blocking agents) should be used with caution. Beta adrenergic blocking drugs add some

further antihypertensive effect to captopril, but the overall response is less than additive.

In heart failure, special caution is necessary since sympathetic stimulation is a vital component

supporting circulatory function and inhibition with beta-blockade always carries a potential hazard

of further depressing myocardial contractility.

Agents Increasing Serum Potassium

: Since captopril decreases aldosterone production,

elevation of serum potassium may occur. Potassium-sparing diuretics such as spironolactone,

triamterene, or amiloride, or potassium supplements should be given only for documented

hypokalemia, and then with caution, since they may lead to a significant increase of serum

potassium. Salt substitutes which contain potassium should also be used with caution.

Inhibitors of Endogenous Prostaglandin Synthesis: It has been reported that indomethacin may

reduce the antihypertensive effect of captopril, especially in cases of low renin hypertension.

Other non-steroidal anti-inflammatory agents (e.g., acetylsalicylic acid) may also have this effect.

The blood pressure lowering effects of captopril and beta-blockers are less than additive.

In patients with renal failure the use of allopurinol concomitantly with captopril has been

associated with neutropenia.

In patients with heart failure, the use of procainamide concomitantly with captopril has been

associated with neutropenia.

Drug/Laboratory Test Interaction: Captopril may cause false-positive reactions for urinary

acetone and for dipstick tests for urinary ketones.


Hypertension and Congestive Heart Failure

Reported incidences are based on clinical trials involving approximately 7,000 patients treated

with captopril.

Renal: Approximately one of every 100 patients developed proteinuria (see WARNINGS).

Each of the following has been reported in approximately 1 to 2 of 1000 patients and are of

uncertain relationship to drug use: renal insufficiency, renal failure, polyuria, oliguria, and urinary


Hematologic: Neutropenia/agranulocytosis has occurred (see WARNINGS). Cases of anemia,

thrombocytopenia, and pancytopenia have been reported.

Dermatologic: A rash occurred in 8.5% of patients with normal renal function and 13% of patients

with evidence of prior renal functional impairment. It was dose related, having occurred in 7% of

patients at doses of 150 mg or less per day. The rash is usually maculopapular, but rarely

urticarial, and generally occurs during the first four weeks of therapy. The rash is usually mild

and disappears within a few days of dosage reduction, short term treatment with an antihistaminic

agent, and/or discontinuing therapy; remission may occur even if captopril is continued. Pruritus,

without rash, occurs in about 2 of 100 patients. Between 7 and 10% of patients with skin rash

have shown an eosinophilia and/or positive ANA titers. A reversible associated pemphigoid-like

lesion, and photosensitivity, have also been reported.


: Angioedema of the face, mucous membranes of the mouth, or of the extremities has

been observed in approximately 1 of 1000 patients, and is reversible on discontinuation of

captopril therapy. Serum sickness and bronchospasm have been reported. One case of

laryngeal edema has been reported.

Cardiovascular: Hypotension may occur: see WARNINGS and PRECAUTIONS (Drug

Interactions) for discussion of hypotension on initiation of captopril therapy.

Tachycardia, chest pain, and palpitations have each been observed in approximately 1 of 100


Angina pectoris, myocardial infarction, Raynaud’s syndrome, and congestive heart failure have

each occurred in 2 to 3 of 1000 patients.

Flushing or pallor has been reported in 2 to 5 of 1000 patients.

Alterations in Taste

: Two percent of patients receiving 150 mg or less per day of captopril

developed a diminution or loss of taste perception. At doses in excess of 150 mg/day, 7% of

patients experienced this effect. Taste impairment is reversible and usually self-limited (2 to 3

months) even with continued drug administration. Weight loss may be associated with the loss of


The following have been reported in about 0.5 to 2 percent of patients:


: gastric irritation, abdominal pain, nausea, vomiting, diarrhea, anorexia,

constipation, aphthous ulcers and peptic ulcer.

Central Nervous System: dizziness, headache, malaise, fatigue, insomnia and


Others: dry mouth, dyspnea, cough, alopecia, impotence, loss of libido, disturbed vision,

and itching and/or dry eyes.

Other clinical adverse effects reported since the drug was marketed are listed below by body

system. In many cases, an incidence or causal relationship cannot be accurately determined.

General: asthenia, gynecomastia.

Cardiovascular: cardiac arrest, cerebrovascular accident, syncope.

Dermatologic: bullous pemphigus, Stevens-Johnson syndrome.

Gastrointestinal: pancreatitis, glossitis.

Hematologic: anemia, including aplastic and hemolytic.

Hepatobiliary: hepatitis, including rare cases of necrosis, cholestasis.

Metabolic: symptomatic hyponatremia.

Musculoskeletal: myalgia, myasthenia.

Nervous/Psychiatric: ataxia, confusion, depression, nervousness, somnolence.

Respiratory: bronchospasm, eosinophilic pneumonitis, rhinitis.

Special Senses: blurred vision.

As with other ACE inhibitors, a syndrome has been reported which includes: fever, myalgia,

arthralgia, rash or other dermatologic manifestations, eosinophilia and an elevated ESR.

Findings have usually resolved with discontinuation of treatment.

Altered Laboratory Findings: Elevations of liver enzymes and/or serum bilirubin have occurred

(see PRECAUTIONS). Rare cases of cholestatic jaundice, and of hepatocellular injury with or

without secondary cholestasis, have been reported in association with captopril administration.

Elevation of BUN and serum creatinine may occur, especially in patients who are volume-

depleted or who have renovascular hypertension. In instances of rapid reduction of long-standing

or severely elevated blood pressure, the glomerular filtration rate may decrease transiently, also

resulting in transient rises in serum creatinine and BUN.

Small increases in the serum potassium concentration frequently occur, especially in patients with

renal impairment (see PRECAUTIONS).

Diabetic Nephropathy

In 400 patients treated with captopril, the overall adverse reactions profile appeared to be similar

to the above. However, the following adverse reactions have occurred more frequently in women

than in men: dizziness (31% vs 20%), cough (23% vs 17%) and pharyngitis (20% vs 14%). In 395

patients treated with placebo, the incidences were: dizziness (22%), cough (15%) and pharyngitis

(11%) in women and men combined.

The incidence of hypotension or orthostatic hypotension was 5.3% and was a reason for

discontinuation of the drug in 1.8% of the patients.

The incidence of hyperkalemia related or possibly related to therapy in the diabetic patients

studied with nephropathy and proteinuria was 3.6% and was a reason of discontinuation of the

drug in 1% of the patients. Hyperkalemia was defined as persistent elevation of serum potassium

to 6.0 mg/dL or more in the absence of a remediable cause, such as other drugs, volume

depletion, exogenous potassium supplements, etc.

In patients with serum creatinine ≥ 1.5 mg/dL, the incidence of a marked abnormality in

hemoglobin (a drop > 3 gram/dL) was 6% in patients treated with captopril versus 0% in those on



In the event of overdosage, correction of hypotension would be of primary concern. Volume

expansion with an intravenous infusion of normal saline is the treatment of choice for restoration

of blood pressure.

Captopril may be removed from the general circulation by hemodialysis.


CAPTOPRIL (captopril) should be taken one hour before meals. DOSAGE MUST BE




Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of

blood pressure elevation, salt restriction, and other clinical circumstances. If possible,

discontinue the patient’s previous antihypertensive drug regimen for one week before starting

captopril. If this is impossible, especially in severe hypertension, the diuretic should be


The initial dose of CAPTOPRIL is 25 mg b.i.d. or t.i.d. If a satisfactory reduction of blood

pressure has not been achieved after one or two weeks, the dose may be increased to 50 mg

b.i.d. or t.i.d. The dose of CAPTOPRIL in hypertension usually does not exceed 150 mg daily.

Therefore, if the blood pressure has not been satisfactorily controlled after one to two weeks at

this dose (and the patient is not already receiving a diuretic), a modest dose of a thiazide-type

diuretic (e.g., hydrochlorothiazide, 25 mg daily) should be added. The diuretic dose may be

increased at one to two week intervals until its highest usual antihypertensive dose is reached.

If CAPTOPRIL is being started in a patient already receiving a diuretic, CAPTOPRIL therapy

should be initiated under close medical supervision (see WARNINGS and PRECAUTIONS (Drug

Interactions) regarding hypotension), with dosage and titration of captopril as noted above.

In severe hypertension, if further blood pressure reduction is required, the dose of CAPTOPRIL

may be increased to 100 mg b.i.d. or t.i.d. and then, if necessary to 150 mg b.i.d. or t.i.d., while

continuing the diuretic. The usual dose range is 25 to 150 mg b.i.d. or t.i.d. A maximum daily

dose of 450 mg given in three equally divided doses should not be exceeded.

For patients with accelerated or malignant hypertension, when temporary discontinuation of

current antihypertensive therapy is not practical or desirable or when prompt titration to more

normotensive blood pressure levels is indicated, diuretic should be continued but other

concurrent antihypertensive medication stopped and CAPTOPRIL dosage promptly initiated at

25 mg t.i.d., under close medical supervision. When necessitated by the patient’s clinical

condition, the daily dose of CAPTOPRIL may be increased every 24 hours under continuous

medical supervision until a satisfactory blood pressure response is obtained or the maximum

dose of CAPTOPRIL is reached. In this regimen, addition of a more potent diuretic, e.g.,

furosemide, may also be indicated.

Beta-blockers may also be used in conjunction with captopril therapy, (see PRECAUTIONS -

Drug Interactions) but the effects of the two drugs are less than additive.

Heart Failure

Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe

salt/volume depletion. In patients with either normal or low blood pressure, who have been

vigorously treated with diuretics and who may be hyponatremic and/or hypovolemic, a starting

dose of 6.25 or 12.5 mg t.i.d. may minimize the magnitude or duration of the hypotensive effect

(see WARNINGS - Hypotension). For these patients, titration to the usual daily dosage can then

occur within the next several days.

For most patients, the usual initial daily dosage is 25 mg t.i.d. After a dose of 50 mg t.i.d. is

reached, further increases in dosage should be delayed, where possible, for at least two weeks to

determine if a satisfactory response occurs. Most patients studied have had a satisfactory clinical

improvement at 50 or 100 mg t.i.d. A maximum daily dose of 450 mg of CAPTOPRIL should not

be exceeded.

Captopril is to be used in conjunction with a diuretic. Therapy must be initiated under very close

medical supervision.

Left Ventricular Dysfunction after Myocardial Infarction

The recommended dose for long-term use in patients following a myocardial infarction is a target

maintenance dose of 50 mg t.i.d.

Therapy may be initiated as early as three days following a myocardial infarction. After a single

dose of 6.25 mg, captopril therapy should be initiated at 12.5 mg t.i.d. Captopril should then be

increased to 25 mg t.i.d. during the next several days and to a target dose of 50 mg t.i.d. over the

next several weeks as tolerated (see CLINICAL PHARMACOLOGY).

CAPTOPRIL may be used in patients treated with other post-myocardial infarction therapies, e.g.

thrombolytics, acetylsalicylic acid, beta blockers.

Diabetic Nephropathy

The recommended daily dose of captopril for long term use to treat diabetic nephropathy is 25 mg

t.i.d. If further blood pressure reduction is required, other antihypertensive agents such as

diuretics, beta adrenoceptor blockers, centrally acting agents or vasodilators may be used in

conjunction with CAPTOPRIL.


Because captopril is excreted primarily by the kidneys, excretion rates are reduced in patients

with impaired renal function. These patients will take longer to reach steady-state captopril levels

and will reach higher steady-state levels for a given daily dose than patients with normal renal

function. Therefore, these patients may respond to smaller or less frequent doses.

Captopril is removed by hemodialysis.

Renal Impairment Due to Diabetic Nephropathy (with or without hypertension)

Captopril at doses of 25 mg t.i.d. was well tolerated in patients with diabetic nephropathy and mild

to moderate renal impairment (see PRECAUTIONS - Hyperkalemia). Accordingly, no dose

adjustment based on creatinine clearance is recommended for these patients.

CAPTOPRIL has not been studied in patients with diabetic nephropathy and severe renal

impairment (creatinine clearance ≤ 30 mL/min/1.73m

). These patients can be expected to have a

higher steady-state concentrations for a given daily dose than those with normal renal function or

mild-moderate renal impairment, and therefore may respond to smaller or less frequent doses.

Doses may be adjusted based on clinical observation.

Renal Impairment Not Due to Diabetic Nephropathy

For patients with significant renal impairment not due to diabetic nephropathy, initial daily dosage

of CAPTOPRIL should be reduced, and smaller increments utilized for titration, which should be

quite slow (one-to two-week intervals). After the desired therapeutic effect has been achieved, the

dose should be slowly back-titrated to determine the minimal effective dose. When concomitant

diuretic therapy is required, a loop diuretic (e.g., furosemide), rather than a thiazide diuretic, is

preferred in these patients with impaired renal function. (See PRECAUTIONS, Anaphylactoid

reactions during membrane exposure)

The following table which is based on theoretical considerations may be useful as a guide to

minimize drug accumulation.

Creatinine Clearance

(mL/min/1.73 m

Dosage Interval


> 75

75 - 35

12 - 24

34 - 20

24 - 48

19 - 8

48 - 72

7 - 5

72 - 108 (3 to 4.5 days)


CAPTOPRIL (captopril) is available as tablets containing:

12.5 mg of captopril - capsule-shaped, white, flat-faced beveled-edged tablets, partially bisected

on both sides. One side engraved PRO, the other side engraved 12.5. Available in bottles of 100

and 500.

25 mg of captopril - square, white biconvex tablets, quadrisected on one side and engraved PRO

over 25 on the other side. Available in bottles of 100 and 500.

50 mg of captopril - oval, white, biconvex tablets, partially bisected and engraved PRO-50 on one

side. Available in bottles of 100 and 500.

100 mg of captopril - oval, white, biconvex tablets, partially bisected and engraved PRO-100 on

one side. Available in bottles of 100.


Drug Substance

Proper Name:


Chemical Name:

1 [(2S)-3-mercapto-2-methylpropionyl] -L-proline

Structural Formula:

Molecular Formula:

Molecular Weight:



White to off-white crystalline powder with a slight acid-sulfhydryl odor;

soluble in water, methanol and ethanol, and sparingly soluble in

chloroform and ethyl acetate. Melts in the range of 104 – 110


In addition to the active ingredient captopril, each tablet contains the non-medicinal ingredients

lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate and colloidal

silicon dioxide.

Stability and Storage Recommendations

Store at room temperature (15 - 30

C). Protect from moisture. Keep bottles tightly closed.


Captopril, administered orally, decreased mean blood pressure in intact spontaneously

hypertensive rats, renal hypertensive rats, and renal hypertensive dogs. Captopril did not lower

blood pressure in spontaneously and renal hypertensive rats that were bilaterally


In anesthetized intact dogs, intravenously administered captopril caused a decrease in blood

pressure, coronary and peripheral vascular resistance, renal vascular resistance, and an increase

in renal blood flow.

Renal blood flow was found to increase following administration of single oral doses of 5 to 25 mg

of captopril to normotensive sodium-depleted or sodium-loaded subjects and to sodium-depleted

hypertensive patients. The greatest increase occurred in the hypertensive patients (average

45%, range 0-73%) while the least increase occurred in the sodium-loaded normotensive

subjects (average 9%, range 8-54%).

In a renal function study in monkeys with hyperplasia of the renal juxtaglomerular apparatus

induced by chronic captopril therapy, the various indices of renal function were not compromised

in comparison with control animals, despite the lower systemic blood pressure and the presence

of the hyperplasia.

Single 100 mg doses of captopril-

C were administered to 15 patients with various degrees of

renal impairment (creatinine clearances ranging from 0 to 56 mL/minute). The blood half-life for

the radioactivity was found to be inversely related to endogenous creatinine clearance with a

linear relationship between creatinine clearance and the overall elimination rate constant for total


In tissue distribution studies in rats, the highest concentrations of orally administered captopril

were found in the kidney, liver, blood and lung.

An increase in cerebral blood flow after captopril administration has been found in spontaneously

hypertensive rats.

In human studies, single oral doses of 2.5 to 20 mg of captopril produced 90 to 100% inhibition of

pressor responses induced by intravenous administration of angiotensin I. Blockade was noted

within 15 minutes. Captopril had no significant effect on the pressor response to angiotensin II.

In clinical studies, during long-term therapy, approximately 80 to 85% of patients with chronic

congestive heart failure exhibited sustained improvement in their functional status and

progressive improvement in their ability to perform treadmill exercise.


Acute Toxicity


Route of Administration





5650 - 7900

600 - 7300




970 - 1130

810 - 1290




270 - 415

340 - 490







Signs of toxicity in mice were respiratory depression, ataxia, convulsions, loss of grip strength,

transient weight loss, edema of tail, collapse, and irritation at the site of intravenous injection.

Signs of toxicity in rats were diarrhea, transient weight loss, cyanosis, ataxia and convulsions.

Most deaths occurred within 1 day.

Résumé: Pertinent Findings in Animals

Chronic oral toxicity studies were conducted in rats (2 years), dogs (47 weeks; 1 year), mice (2

years), and monkeys (1 year). Significant drug-related toxicity included effects on hematopoiesis,

renal toxicity, erosion/ulceration of the stomach, and variation of retinal blood vessels.

Reductions in hemoglobin and/or hematocrit values were seen in mice, rats, and monkeys at

doses of 500 to 1500 mg/kg/day. Anemia, leukopenia, thrombocytopenia, and bone marrow

depression occurred in dogs at doses of 80 to 300 mg/kg/day. The reductions in hemoglobin and

hematocrit values in rats and mice were only significant at 1 year and returned to normal with

continued dosing by the end of the study. Marked anemia was seen at all dose levels (80 to 300

mg/kg/day) in dogs, whereas moderate to marked leukopenia was noted only at 150 to 300 mg/kg

and thrombocytopenia at 300 mg/kg. The anemia could be reversed upon discontinuation of

dosing. Bone marrow suppression occurred to a varying degree, being associated only with dogs

that died or were sacrificed in a moribund condition in the 1-year study. However, in the 47-week

study at a dose of 300 mg/kg/day, bone marrow suppression was found to be reversible upon

continued drug administration.

Captopril caused hyperplasia of the juxtaglomerular apparatus of the kidneys at doses 70 to 2000

mg/kg in rats and mice, at 200 to 600 mg/kg in monkeys and at 200 mg/kg/day in dogs.

Gastric erosions/ulcerations were increased in incidence at 200 and 2000 mg/kg doses in male

rats and at 300 and 650 mg/kg doses in dogs and monkeys, respectively. Rabbits developed

gastric and intestinal ulcers when given oral doses of approximately 300 mg/kg for only 5 to 7


In the two-year rat study, irreversible and progressive variations in the caliber of retinal vessels

(focal sacculations and constrictions) occurred at all dose levels (70 to 2000 mg/kg/day) in a

dose-related fashion. The effect was first observed in the 88th week of dosing, with a

progressively increased incidence thereafter, even after cessation of dosing.

Subacute Toxicity



Number of

Animals per







Duration of


Toxic Effects



0, 50, 150, 450, or 50-

3000 (progressively

increasing doses)


1 month

High Dose: slight growth retardation

(females only); slightly decreased

erythrocytic parameters; slight leukocytosis.

Three Highest Doses: slight to moderate

increase in BUN; dose-related slight to

moderated retardation (males only).

All Doses: slightly increased water intake.


0, 25, 75, 225


1 month

High & Mid Doses: decreased erythrocytic

parameters; increased urine calcium.

All Doses: Increased urine magnesium

(significant only in mid-dose group).


2, 3

2, 3

0, 200-600

(i.e wk 1 = 200,

wks 2-4 = 400,

wk 5 = 600)


5 weeks

200 mg/kg: decreased food consumption

and body weight (females only); slight

increase in BUN.

400 mg/kg: 1 death and 3 sacrifices due to

G.I. distress and kidney dysfunction.

600 mg/kg: (2 remaining dogs); occasional

emesis and loose feces; slight to moderate

increased BUN, creatinine, total protein,

potassium, calcium and cholesterol.



0, 25, 75, 225


1 month

No toxic effects.



0, 50, 150, 450


3 months

High Dose: Loose feces, decreased weight

gain and erythrocytic parameters: increased

BUN, sodium & retention of BSP.

High & Mid Doses: Dose-related mild to

moderate hyperplasia of juxtaglomerular


Chronic Toxicity and Carcinogenicity



Number of

Animals per







Duration of


Toxic Effects




0, 50, 150,



2 years

High Dose: slight retardation of body-weight gain

(males only); slight increase of serum alkaline

phosphatase (females only).

All Doses: slight decrease in erythrocytic parameters

& slightly lower heart weight and hyperplasia of renal

juxtaglomerular apparatus.

No evidence of carcinogenicity was observed.



0, 50, 150,



2 years

High Dose: slight increase in SGPT; slight increase

in BUN (females only).

All Doses: slight to moderate retardation of body

weight gain; very slight decrease in erythrocytic

parameters (dose-related) and serum total protein;

slight dose -related increase in BUN (males only);

lower mean heart weights; dose-related changes in

retinal vessels, thickening of renal afferent arterial

walls due to hyperplasia of juxtaglomerular and

arterial smooth muscle cells.

No evidence of carcinogenicity was observed.


0, 50, 100, 200


1 year

High Dose: 1 sacrificed with renal dysfunction-

marked tubular dilation and mild hyperplasia of

juxtaglomerular apparatus; slight increase in BUN.

High & Mid Doses: emesis.

All Doses: bone marrow suppression involving

myeloid and/or erythroid series- 5 dogs sacrificed or

died; anemia.



47 weeks

Effects reported in previous study corroborated.



13, 7

7, 9

0, 50, 150, 450


1 year

High Dose: loose feces, slight increases in serum


High & Mid Doses: slight decreases in erythrocytic

parameters and serum sodium; slight to moderate

increases in BUN; hyperplasia of juxtaglomerular


Reproduction and Teratology




Number of

Animals per









Toxic Signs



0, 50, 300, 1800,


0, 50, 300, 1800,


10 weeks prior to mating

2 weeks prior to mating.

Dosing continued in half

of females until Day 13 of

gestation. Remaining

females dosed through

gestation and 21 days of



No effects on fertility and reproduction;

no embryotoxic fetotoxic, or

teratogenic effects.



19 - 22

0, 50, 450, 4000

Days 7 through 16 of



Mean food consumption and body

weight gain significantly reduced in

4000 mg/kg group. 6 deaths of

mothers due to gastric ulceration (5

from high-dose group). No

embryotoxic, fetotoxic or teratologic





24, 24, 24,

26, 8, 6

0, 50, 450, 1000,

2000, 4000

Days 7 through 13 of



Death due to gastric ulcers in 12 of 14

dams at 2000 and 4000 mg/kg. 88%

incidence of embryonic death in 2

remaining dams at 2000 mg/kg. No

embryotoxic, fetotoxic or teratologic

effects at doses of 1000 mg/kg.




15 - 20

0, 0, 15, 50, 150, 450

Days 7 through 19 of



Gastric ulcers (6 to 19% incidence) in

all dosed does; dose-related

incidences of fetal death in all treated

groups - thought due to hypotension

(dose-related) in does rather than

direct fetotoxic effect; hydrocephalus

(2%) and microphthalmia (2.7%) in

fetuses of 3 lower dose groups.



16 - 23

0, 50, 400, 3000

Day 15 of gestation

through Day 21 of



Reduced postnatal growth and viability

of offspring of one dose group.


1. Aberg H., Frithz G., Morlin C. Comparison of captopril (SQ 14,225) with hydrochlorothiazide in

the treatment of essential hypertension. Int. J. Clin. Pharmacol. Ther. Toxicol. 19:368-371, 1981.

2. Ader R., Chatterjee K., Ports T., Brundage B., Hiramatsu B., Parmley B. Immediate and

sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-

converting enzyme inhibitor. Circulation 61:931-937, 1980.

3. Atkinson A.B., Brown J.J., Lever A.F., Robertson J.I.S. Combined treatment of severe

intractable hypertension with captopril and diuretic. Lancet 2:105-108, 1980.

4. Atkinson A.B., Robertson J.I.S. Benefits versus risks of captopril therapy. In: Recent Advances

in Hypertension Therapy: Captopril H.R. Brunner & F. Gross eds. Amsterdam: Exerpta Medica

1981, pp. 50-69.

5. Awan N.A., Amsterdam E.A., Hermanovich J., Bommer W.J., Needham K.E., Mason D.T.

Long-term hemodynamic and clinical efficacy of captopril therapy in ambulatory management of

severe chronic congestive heart failure. Amer. Heart J. 103(4):474-479, 1982.

6. Bravo E.L., Tarazi R.C., Fouad F.M. Hemodynamic effects of long-term captopril therapy in

hypertensive man. In: Angiotensin Converting Enzyme Inhibitors - Mechanisms of Action and

Clinical Implications. Z.P. Horovitz, ed. Baltimore: Urban and Schwarzenberg, 1981, pp. 263-272.

7. Captopril Collaborative Study Group. Does captopril cause renal damage in hypertensive

patients? Lancet 1:988-990, 1982.

8. Case D.B., Atlas S.A., Marion R.M., Laragh J.H. Long-term efficacy of captopril in renovascular

and essential hypertension. Am. J. Cardiol. 49:1440-1446, 1982.

9. Chatterjee K., Rouleau J.L.Hemodynamic and metabolic effects of vasodilators, nitrates,

hydralazine, prazosin and captopril in chronic ischemic heart failure. Acta. Med. Scand. (suppl.)

651:295-303, 1981.

10. Chatterjee K., Rouleau J.L., Parmley W.W. Hemodynamic and myocardial metabolic effects

of captopril in chronic heart failure. Br. Heart J. 47:233-238, 1982.

11. Cowley A.J., Stainer K.L., Rowley J.M., Hampton J.R. Captopril therapy for heart failure. A

placebo controlled study. Lancet 2: 730-732, 1982.

12. Drayer J.I.M., Weber M.A. Monotherapy of essential hypertension with a converting-enzyme

inhibitor. Supp III Hypertension 5(5): III-108 - III-113, 1983.

13. Ferguson R.K., Rotmensch H.H., Vlasses P.H. Clinical use of captopril. J.A.M.A. 247(6):2117-

2119, 1982.

14. Ferguson R.K., Vlasses P.H., Koplin J.R., Shirinian A., Burke J.F. Jr., Alexander J.C.

Captopril in severe treatment-resistant hypertension. Am. Heart J. 99:579-585, 1980.

15. Gronda E., Brusoni B., Mangiovacchi M., Oppizzi M., Inglese E., Caroli A. and Rovelli F.

Haemodynamic, Radionuclide Ventriculography and Ergometric Evaluation of Captopril

Treatment in Congestive Heart Failure. Postgrad. Med. J. 62(Suppl. 1): 167-169, 1986.

16. Jenkins A.C. Captopril in Hypertension: Seven Years Later. J. Cardiovasc. Pharmacol. 7:S96-

S101, 1985. 17. Lewis E.J., Hunsicker L.G., et al The Effect of Angiotensin-Converting Enzyme

Inhibition on Diabetic Nephropathy. N. Engl. J. Med. 329:1456-1462, 1993.

18. MacGregor G.A., Markandu N.D., Banks R.A., Bayliss J., Roulston J.E., Jones J.C.Captopril

in essential hypertension: contrasting effects of adding hydrochlorothiazide or propranolol. Br.

Med. J. 284:693-696, 1982.

Magnani B., Magelli C. Captopril in Mild Heart Failure: Preliminary Observations of a Long-

Term, Double-Blind,


Controlled Multicentre Trial. Postgrad. Med. J. 62(Suppl. 1), 153-

158, 1986.

20. Maskill M.R., Orme M.L.E., MacIver M., Serlin M.J., Breckenridge A.M. Efficacy and adverse

effects of captopril in severe refractory hypertension. J. Cardiovasc. Pharmacol. 3:1287-1295,


21. Mason D.T. New strategies in the management of severe chronic heart failure: captopril.

American Heart Journal 104(5) (Part 2):1125-1228, Nov. 1982.

22. Massie B.M., Conway M. Survival of patients with Congestive Heart Failure: Past, Present

and Future Prospects. Circulation 75(suppl. IV): IV II-IV19, 1987.

23. Massie B., Kramer B.L., Topic N., Henderson S.G. Hemodynamic and radionuclide effects of

acute captopril therapy for heart failure: changes in left and right ventricular volumes and function

at rest and during exercise. Circulation 65:1374-1381, 1982.

24. Millar J.A., McGrath B.P., Matthews P.G., Johnston C.I. Acute effects of captopril on blood

pressure and circulating hormone levels in salt-replete and depleted normal subjects and

essential hypertensive patients. Clin. Sci. 61:75-83, 1981.

25. Moyé, L.A. et al. Rationale, design and baseline characteristics of the survival and

ventricularenlargement trial. Am. J. Cardiol. 68:70D-79D, 1991.

26. Pfeffer M.A. et al. Effect of captopril on progressive ventricular dilatation after anterior wall

myocardial infarction.

N. Engl. J. Med. 319: 80-86, 1988.

27. Pfeffer M.A. et al. Effect of captopril on mortality and morbidity in patients with left ventricular

dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial.

N. Eng. J. Med. 327:669-677, 1992.

28. Rouleau J.L., Chatterjee K., Benge W., Parmley W.W., Hirainatsu B. Alterations in left

ventricular function and coronary hemodynamics with captopril, hydralazine and prazosin in

chronic ischemic heart failure: a comparative study. Circulation 65:671-680, 1982.

29. Sharpe N. et al. Treatment of patients with symptomless left ventricular dysfunction after

myocardial infarction. Lancet: 255-259, February 6, 1988.

30. Sharpe D.N., Coxon R.J., Douglas J.E., Long B. Low-dose captopril in chronic heart failure:

acute haemodynamic effects and long-term treatment. Lancet 2:1154-1157, 1980.

31. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Captopril:

evaluation of low doses, twice-daily doses and the addition of diuretic for the treatment of mild to

moderate hypertension. Clin. Sci. 63:443S-445S, 1982.

32. Product Monograph –PrCAPOTEN™ (captopril) Tablets, USP, 12.5, 25, 50 and 100 mg.

Bristol-Myers Squibb Canada, Date of Revision: 8 November 2006

Similar products

Search alerts related to this product

Share this information