Captoprills a specific competitive inhibitor of angio!erlSln I-converting enzyme (ACE), the enzyme responsible for the conversion of

anglolensln Iloanglolensin II.

eaploprills deslgnaled chemically as j-[(2S)-3-mercaplo-2-malhylpropionylj-L-prolina. Moler:ular fonnul. e,H'NO,S [MW 217.29) and

has the follo"NIngstruclural.formula:

Captoprills a white to off-white crystalline powder that may have a slight sulfurous odor; it is soluble in waler (approx. 160 m9fml),

malhanol, and alhanol and sparingly soluQleln chIorolonn and alhyl acelala.

Each scored tablet, for oral administration, contains 12.5 mg, 25 mg, 50 mg or 100 mg of captopril.ln add~ion, each lablet contains the

following inactive ingredients: microcf)"stalline cellulose,comstarch, anhydrous ladose, coHoidalsilicon dioxide, talc andpalmilic acid.

Mechanism of Action

ThE"t m~chanism 01 action of captopriJ has not yet been fully elucidated. lis-beneficial effects In hypertension and heart failure appear 10

result primarily from suppression of the reninwangiolensln-aJdosterone system. However, there is no consistent correlallon between

renin levels and response 10 Ihe drug. Renin, an enzyme synthesized by Ihe kidneys, is released into the circulation where it acts on a

plasma globulin $ub~trate to produce angiotensinl, 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 sodiumand fluid retenllon. .

Caplopril prevents the conversion of angiotensin Ito angiotensin II by inhibition of ACE, a peplidyldipeplide carboxy hydrolase. Thls

inhibition has been demonstrated in both heallhyhuman subjects and in animals by showing that the elevation of blood pressure caused

by exogenously adminlstered angiotensin Iwas attenuated or abolished by captopril.lnanimal studies, captopril did notaltertha pressor

lasponses to anumber 01 other agents, Including angiotensin II andnorepinephrine, Indicating specificity 01 action.

ACE Is Identical to 'bradykinlnase", and captopril may also interfere with the degradation of tho vasodepressor peptide, bradykinin.

IncreasedconcenlraUons of bradykinin Of prQstaglandin E2 mayalsohave arole In the therapeutic e~ecl ofCaptopril.

Inhibition of ACE results In decreased plasma aogiolensln II and increased plasma renin activity (PRA), the laller resulting from loss of

negative feedback on rennin release caused by reduction in angiotensin II. The reducllon 01 angiotensin II leads to decreased

aldosterone secretion, and, asaresull, 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 ls lnhlb~ed longer than the ACE In circulating blood.

Hypertension: Captopril tablets US?are indicated for the Teatment of hypertension.

tn using captopril, conslderallon should be gtven to the risk of neutropenia!agranutocytosls (seeWARNINGS).

Captoprll maybe used as Initial therapy for patientswilh normal renal function, In whomthe rlskls relatively low. In patients with impaired

renal function, particularly those wfth collagen vascular olSeas6, captopril should be reseNed for,hypertenslves who have either

develoPed unacceptable side effecls on otherdrugs, orhave failed to responq satislactorily 10drug cOmbinations.

Captopril is effective alone and in combination with other antihypertensive agents, ~peclally thiazide-type diuretics. The blood pressure

lowering effecls of captoprif and thlazldes are approximalaly a<!dlltva.Heart Failure:Captopril tabletsare indicated in the treatmentof congestive heart failure usually in cornblnatlpn with

diuretics and

di9italls_ The beneficial effect 01 captopril in~eart failure does notrequl.re the presence 01 digllaUs, however, most controlled cliniCal trial

experience with captopril has been in paUentsreceMng digitalis, as well as dluretlctrealmen!. .

Left V~ntrlcular Dysfunction After MYQcar~lal tnlarctlon : Gaplopril tablels are indicated to Improve survival following myocardial

fnfarclion In clinically stable patients with left ventriCUlardysfUnction manlfesled as an ejection fraction ::;40% and 10 reduce the Incidence

01 overt heart failure and subsequenthospitalizations forcongesUve heart failure In these patients.

Diabetic Nephropathy: Captopril lablels are indicated fortha trealment ot diabetic nephropathy (proteinuria> 500 mg/day) in paUents

with type Ilnsulin-dependenl diabetes mellitus and retinopathy. Caplopriltablets decreases the rate of progression of renallns·uffJcienCy

and development of serious adverse clinical outcomes {death or need for renallransplantation or dialysisl.

In considering use of caplopril tablets, it should be noted that In controlled trtals ACE inhibllors have an effect on blogd pressure that is

less in black patients than In nonblacks. In addition, ACE Inhibitors (for which adequate data are available) cause a higher rate of

angioedema in black than In non-black palients {seeWARNINGS: Head and NeckAngloedema and Intestinal AngIQedema}.

Captopril tablets are contraindicatedin patients who are hypersensitive to this product or any other anglolensln. converting enzyme inhibitor

(e.g., a patient who has experienced angloedema during therapy with any other ACE inhibitor).

Anaphylaclold and Possibly Related Reactions

Presumably because angiotensln·converting enzyme inhibitors affect the metabolism of elcosanoids and polypeptides, inclUding

endogenous bradykinin, patients receiving ACE}nhibitors (including caplopril) may be subject to avariety 01 adverse reactions, some of

them serious.

Headand Neck Angioedema: AngioedemaInvolving the extremities, face, Ij~, mucous membranes, longue, glottis or larynx has been

seen In patients Irealed with ACE inhibitors, Including captopril. If angioedema Involves the tongue, glottis or larynx, airway obstruction

may occur and be falal. Emergencytherapy, including but not necessarily limited 10, sUbculaneous administration of a1:1000 solution of

epinephrine should be prompUyinsUtuted.

Swelling confined to ~_e face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuatJon of

captopril; some cases required medlcallherapy. (See PRECAUTIONS: Information for Patients and ADVERSE REACTIONS.)

Intestinal Angioedema: Intestinal angioedema has been reported in patients trealed wah ACE lnhibil.ors. These patients presenled

with abdominal pain (with or without naUSeaorvomiting); in somecasesIherewas noprior history of facial angioedemaandC·l esterase

levels were normal. Thf! angioedema Vias diagnosed by procedures Including abdominal CT scan or ultrasound, or at surgery, and

symploms resolved after slopping the ACE inhibitor.lnlestinal angioedema shouldbe Included In the dillerential diagnosis of patlents on

ACEInhibitorspresenting with abdominal pain.

Anaphylactoid reactions during desensitization: Two patienls undergoing desensitizing lreatment wilh hymenoplera venom while

receiving ACE Inhibitors suslained liIe-threatenlng anaphylactoid reactions. In the same patients, these reacUonswere avoided When

ACE inhibilors were temporarity wHhheld, butthey reappeared uponinadvertentrechallenge.

Anaphylactoid reactions during membrane exposure: Anaphylactoid reactions have been reported in pauenls dIalyzed with highflux

membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patienls

undergoing low-densitylipoproleln apheresls with dextran sulfate absorption.

Neutropenia/Agranulocytosis

Neutropenia «1OOO!mm~ with myeloid hypoplasia has resulted from use of caplopril. About hal( of the neutropenic patients developed

syslemic or oral cavity inlecUons or other features Qf the syndrome of agranUlocytosis.

The risk of neutropeniais dependenton the clinical status of the paUent :

In clinical trials inpatients with hypertension who have normal renat function (serum creatinine less than 1.6 ml}'dL and no collagen

vascular disease), neutropenia hasbeen seenin one patient oul of over 8,600 exposed.

In patienls with some degree of renal failure (serum creatinine at least 1.6 mgldl) but no collagen vascular disease, the risk of

neutropenia in cl!nicallrials was about 1per 500, afrequency over 15 times that for uncomplicated hYpertension. Dally doses of

caplopril were relatively highin these patients, p~rticulartyln view of Ihelrdiminished renal function. In foreign markeling experience

In patients wilh renal fallure, use of allopUrinol concomitantly with caplopril has been assoclaled with neutropenIa but this

association has notappeared in U.S. reports.

In patient& with collagen vascular diseases (e.g' systemic lupus el)"thematosus, scleroderma) and impaired renal function,·

neutropenia occurred in 3.7 percent oipalients In c1inicat trials.

While f1pne of the over 750 patlents In formal clinlcallrials of heart failure .developed neulropenla, it has occurred during the

subsequent clinical experience. About half of the reported cases had &erurn creatinine ~1.6 mgldL and more than 75 percent were In

patlenls also receiving procainamide.ln heart failure, itappears thatlhe same risk factors for neutropenia are present.

The neutropenia has usually been detected within three months alter caplopril was started. Bone marrow examinations in palienls with

neutropenia consistently showed myeloId hypoplasia, frequently accompanied by erythroid hypoplasia and decreased numbers of

megakaryocytes (e,g' hypoplasticbone marrowand pancytopenia); anemia and thrombocytopenia were sometimes seen.

In general, neutrophlls returried to normal in about two weeks after captopril was discontinued,·and serious infections Were limned to

clinically complex patients. About 13 percent oIlhe cases of neutropenia have eooed fatally, but afmostall falalitles were In patients with

serious illness, having collagen vascular disease, renalfaHure, heart failure or immunosuppressant therapy, or acombination of these

complicalingfactors.

Evaluation of the hypertensive orheart failure pallent should always Include assessmenl of renal function.

If captoprills used In patients with ImpaIred renal function, white blood cell and differenllal counts shoUld be evalualedpn"orto starting

treatment and at approxlmalely two·weekIntelvels foraboul three monlhs, Ihen periodically.

In patients with collagen vascular disease or Who are exposed to other drugs known to affect the while 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 Ireated wilh capt~'" shouldbe told to report any signs of Infection (e.g., sore Ihroat, fever). 'infection Is susPected, white cell

counts should be performed without delay,

~ince discontinuation of captopril and other drugs has genera/ly led to prompt relurn of the white count to normal, upon confirmation of

neutropenia(neutrophil count<1OOOImm~ Ihe physlcien should wilhdraw captopol and closely follow the patienrs course.

Proteinuria

Total urinary proteins greater than 1gperday were seen in about 0.7 percentaf patients receiving captopril. Aboul90 petcentofaffected

patlents had evidence of prior renal disease or received relatively high doses of captopril (in excess 01150 rng/day), or both. The

nephrotic syndrome occurred In aboul one·fifth of protelnuric patients. In most cases, proteinuria subsided or cleared within six months

whether or not captopril was continued. Parameters of renal function, such as BUN and creatinIne, were s~ldom altered In the patients

with proteinuria.

Hypotension

Excessive hypotension was rarely seen in hypertensive paUenls but is apossible consequence of captopril use in salVvolume depleted

persons (such as those treated vigorously with diurelics), patients with heart faflure or those paUenls undergoing renal dialysis (see

PRECAUTIONS: Drug Interactions.)

In heart failure, where the blood pressure was elther nonnal or low, lranslentdecreases In mean blood pressure greater than 20 percent

were recorded in about half of the patients. This transient hypotension is more likely 10 occur after any of the first several doses and Is

usually welliolerated, producing

either no symptoms or brief mUd IIghUleadedness although,

In rare Instances it has been assoclaled with arrhythmia or conduction defects. Hypotension was the reason for discontinuation of drug in 3.6 patients with heart failure.

BECAUSE OFTHE POTENTIAL FALL IN BLOOD PRESSURE IN THESE PATIENTS, THERAPY SHOULD BE STARTED UNDER

VERY CLOSE MEDlCA~ SUPERVISION.

Astarting dosa of 6.25 or 12.5mg t.i.d. may minimize the hypotensive effect

Pellents should

be followed closely for the first two weeks of treatment and whenever the dose of captopril and/or diurelic Is increased. In patients with

hearffailure, reducing the dose of diuretic, if feasible, mayminimize the fall in blood pressure.

Hypotension is not per se a reason to disconlinue captoprll. Some decrease of systemic blood pressure is acommon and desirable

observation upon initiation of caploprillablets, USP treatment in heart failure. The magnItude of the decrease Is greatesl earty in the

course of treatment; this effect stabHizes within a week or two, and generally relums to prelreatmentlevels, without a decrease in

therapeutic efficacy, wilhlntwomonlhs.

FetallNeonatal MorbiditY and Mortality

ACE inhibitors can cause fetal and neonalal morbidity and death when admlnlslered to pregnant women. Several dozen cases have

been reported In the world literature.WhenpregnancyIs delected,ACE inhibitors should bediscontinuedas soon as possible.

The use of ACE InhIbitors during the second and third trimeslers of pregnancy has been associated with fetal and neonatal injury,

Including hypolension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure. and death. OligohydramnIos has also

been reported, presumably resulling from decreased fetal renal function; oligohydramnios

in this selling has been assoclated with fetal

limb cootraclures, craniofacial defonnalfon, and hypoplastic lung developmenl. Premalunty, Intrauterine growth retardation, and patent

ductus. arteriosus havEl alsobeen reported, althougbJt Is notdear'Yheth.er ~~~e opcurrences were dueto the ACE·inhlbltor exposure.

These adverse effects do notappear to have resulted from Intraulerine ACE·inhibitor exposure that has been limited to the first trimester.

Mothers whose embryos and fetuses are exposed to ACE inhlbilors only during the first trimester should be so Informed Nonetheless,

when patients becomepregnant, physicians shouldmake every effort to discontinue the use 01 captopril as soon a~ possible.

Rarely (probably less often than once In everylhousand pregnancies), no alternative toACE lnhlbll6ts will be found. In these rare cases,

the molhers should be apprised of the potential hazatds to their feluses, and serial ultrasOund examinations should be peJfOlmed to

assess the Intraamnlotlcenvironment.

If oligohydramnios is obselVed, caploprilshould be discon~nued unless it is considered life.saving for lhe mother. Contraction stress

lesting{CST}, a non-stress tosl (NST), or biophysical profiling (BPP) may be approprtate, depending upon the weak 01 pregnency.

Patients and physldans should be aware, however,that oligohydramnios may nol appear unl!! after the fetus has sustained Irreversible

InJury.

Infants with histories of in utero expOsure to ACE inhibitors should be closely observed for hypolension, oliguria, and hyperkalemia. If

oliguria occurs. atlention.should be directed toward support of blood pressure and renal perfusion. Exchangetransfusion or dialysis may

be required as ameans of reversing hypotension and/or sUbsli!utingIor disordered renal fuoction. While captopril maybe removed from

the adult circulation by hemodialysis, there is inadequate data concerning the effectiveness of hemodialysis for removing it from the

clrculalion ofneonates orchildren. Peritoneal dialysis is not effective for removing captopril; there is no Informationconcerning exchange

transfusion for removing captopril from the general circulation. ".

When caplopril was given to rabbits at doses about 0.8 to 70 Urnes (on amglkg basis) the maximum recommended human dose, low

incidences of craniofacial malformations were seen. No teratogenic effects of captopril were seen In studies of pregnant rats and

hamsters. On amg!k:g basts, the doses used were up to 150 times (in hamsters) and 625 times ~n rats} the maximum recommended

humandose.

Hepatic Failure

Rarely, ACE inhibitors have been associated with asyndrome that starts with cholestaUc Jaundice and progresses to fulminant h!3psllc

necrosis and {sometimes} death. The mechanism of this syndrome Is not understood. Patienls receMng ACE inhibitors who develop

Jaundice or marked elevations of hepaticenzymesshould discontinue theACEinhlbllorand receive appropriate medical follOW-Up.

Reported incidences are based on clinical trials involving approximately7000 patients.

Renal: About one of100 pallenls develope<iprolelnuna (seeWARNINGS),

About one of100 pallenls develope<iprolelnuna (seeWARNINGS),

Each of the following has been reported in approximately 1 102 of 1000 patients and are of uncertain relationship 10 drug use: renal

Insufficiency. r~nal faHure, nephrotic syndrome, polyuria, oliguria, andurinary frequency. . . .

Hematoldgic: Neutropenia/agranulocytosis has occurred (see WARNINGS). Cases of anemia, thrombocytopenia, and pancytopenia

Neutropenia/agranulocytosis has occurred (see WARNINGS). Cases of anemia, thrombocytopenia, and pancytopenia

havebeenreportedt

Detmaf9foglc :R~h, otten Vvilh pruritus, and sometimes with fever, arthralgia, and eosinophilia, occurred in about 410 7 (depending on

:R~h, otten Vvilh pruritus, and sometimes with fever, arthralgia, and eosinophilia, occurred in about 410 7 (depending on

renal status and-dose) 01100 patients, usually dUring the first four weeks of therapy. It is usually maCUlopapular, and rarely urUcarial. The

rash is usually mild and disappears within a few days of dosage ~eduction, short-tenn treatmenl with an anUhlstaminic agent, and/or

disconlinuing therapy; remission mayoccur even lfcaptoprills conllnued.Prurilus, without rash, occurs in about2 of 100patients. Between

7and 10 percenl of patients with skin rash haveshown an eosinophilia and/or positive ANA titers. Areversible associated pemphigoid-like

lesion, and photosensitivity, have alsobeen reported. '

Flushing orpallorhasMenreported In 2to5of1000patlenls.

Cardiovascular: Hypotension may occur; see WARNINGS and PRECAUTIONS (Drug Interactions) for discussion of hypotension with

Hypotension may occur; see WARNINGS and PRECAUTIONS (Drug Interactions) for discussion of hypotension with

captoprlilherapy,

Tachycardia, Chest pain, andpalpitations have eachbeenobseNed in approximately1of100 patients.

Angina pectoris, myocardiallnfarclion, Raynaud"s syndrome, and congestive heart failure have each occurred ln2lo 3 of 1000patients.

Dysgeusia: Approximately 2to 4(depending on renal status and dose) of 100pallents developed adiminution or loss of taste perception.

Approximately 2to 4(depending on renal status and dose) of 100pallents developed adiminution or loss of taste perception.

Taste impairment Is reversible and usually self·l1mited (2 to 3 months) even with coolinued drug adminiStration. Weighlless-may be

assoclatedwiththelossottasle.

Angioedema: Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been reported in

Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been reported in

approxImately one In 1000 patrents. AngIoedema Involving lhe"'upperaiWiays lias caused fatal airway obstruction. (See WARNINGS:

Head and NeckAngloedema Intestinal Angioedema and PRECAUTIONS: Information for Patients.)

Cough:Cough has been reported In 0.5 -2% of patients treated with captopril inclinicat trlals(see PRECAUTIONS: General, Cough)

:Cough has been reported In 0.5 -2% of patients treated with captopril inclinicat trlals(see PRECAUTIONS: General, Cough)

The following have been reported in about 0.5 to 2 percent of patients but did not appear at Increased frequency compared to placebo or

other treatments used In controlled trials: gastric irritation, abdominal pain, nausea, vomiting, diarrhea, anorexia, constipation, aphthous

ulcers, pepticulcer,dizziness, headache, malaise,1atigue, insomnia, drymouth, dyspnea, alopecla, parestheslas.

Other clinical adverse effects reported sInce the drugwas marketed are listed below by body system, In this selting, an incidence or causal

relationship cannot be accurately determined.

Body as B whole: Anaphylactoid reactions (see WARNINGS: Anaphylactoid and possible related reactions and PRECAUTIONS:

as B whole: Anaphylactoid reactions (see WARNINGS: Anaphylactoid and possible related reactions and PRECAUTIONS:

Hemodialysis),

General:Asthenia, gynecomastia.

Asthenia, gynecomastia.

Cardiovascular: Cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.

Cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.

Dermafologic: Bullous pemphigus, erythemamulliforme (including Slevens-Johnson syndrome), exfoliative oormalitis,

Gastrointestinal Pancreatitis, glossitis, dyspepsia,

Hematologic:AnemIa, Including aplastic and hemolytic.

AnemIa, Including aplastic and hemolytic.

Hepatobi/lary:Jaundice, hepatitis, Including fare cases of necrosis, cholestasis.

Jaundice, hepatitis, Including fare cases of necrosis, cholestasis.

MelaboflC:Symplomatichyponatremla. '

Musculoskelela/:Myalgia, myasthenia,

NelVouslPsychiatric: Ataxia, confusion, depression, nervousness, somnolence.

Ataxia, confusion, depression, nervousness, somnolence.

Respirafo/)":Bronchospasm, eosinophilic pneumonitis, rhinitis.

Bronchospasm, eosinophilic pneumonitis, rhinitis.

Specla/Senses:Bfurredvlsion.

Urogenital:lmpotence.

As with otherACE inhibitors, asyndrome has been reported which may include; lever, myalgia, arthralgia, inlerstitial nephritis, vasculitis,

rash or other dermatologicmanifestations, eosinophilia and an elevated ESA.

FetallNeonatal Morbidityand Mortality

See WARNINGS: FataUNaonetat Morbldltyand Mortality,

Altered Laboratory Findings

SewfTJ Elecfrolytes: HyperkafemJa: small increases in serum potassium, especially in patients' with renal Impairment (see

small increases in serum potassium, especially in patients' with renal Impairment (see

PRECAUTIONS),

Hyponatremfa: Particularly in patients receiving alowsodium diet or concomitantdiuretics,

Particularly in patients receiving alowsodium diet or concomitantdiuretics,

BUN/Serum Creatinine: Transient elevations of BUN or serum creatinine especially in volume or salt depleted patients or those with

Transient elevations of BUN or serum creatinine especially in volume or salt depleted patients or those with

renovascular hypertension may occur. Rapid reduction of longstanding or markedly elevated blood pressure can result in decreases in the

glomerular filtration rale and, In lum,lead to Increases inBUNor serum creatinine.

Hemalologlc:AposKIv~ANAhasbeen reported,

AposKIv~ANAhasbeen reported,

UverFunctionTesls: Elevallons of liver transaminases, alkaline phosphatase, and serum biirubin have occurred.

Elevallons of liver transaminases, alkaline phosphatase, and serum biirubin have occurred.

Correction of hypotension would beof primary concern. Volume expansion with an intravenous infusIon of normal saline Is the treatment of

choice for restoration of blood pressure.

While captopril may be remOved from the'adult cIrculation by hemodialysis, there is Inadequate data concerning the effectiveness of

hemodialysis for removing it from the circulation of neonates or chfldren. Peritoneal dialysIs is not effeclive for removing captopril; there is

no information concerning exchange transfusion for removing captopril from the general circulation.

Caplopril tablets should be taken one ho.ur before meals. Dosage mustbe individualized.

Hypertension· Inlliation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure

elevation, salt restriction, and other clinical circumstances. Ifpossible, discontinue the paUenfs prf?vious antihypertensive drug regimen for

one weekbefore starting captopril.

The initial dose of captopril tablels US?is 25mgb.l.d. orUd.1f satisfactory reduction of blood pressure has not been achieved after one or

two weeks, the dose may be increased 10 50 ffig b.l.d. or t.l.d. Concomitant sodium restrictfon may be beneficial when caploprills used

alone.

The dose of caplopril in hypertension usually does not exceed 50 mg t.i.d. Therefore, if the blood pressure has not been satisfactorily

controlled after one to two weeks at this dose, (and the patrent is nol already receiving adiuretic), a modest dose of thIazide-type diuretlc

(e.g., hydrochlorolhiazide, 25 mg daily), should beadded. The diureticdose may be increased at one-Io two-week intervals untilits highest

usual antihypertensive dose isreached.. .

If cap!opril is beIng starte~ in a patient already receiving adiuretic, captopriliherapy should be iniUaled under close medical supervision

(see WARNINGS and PRECAUTIONS: Drug Interactions regarding hypotension), wiih dosageandtilration of caplopol as notedabove.

l{ further blood pressure reduction Is required, the dose of captopril may be Increased to 100mgb.l.d. orUd. aodthen, if necessary, to 150

mg b.l.d. or t.l.d . (while continuing the diuretic). The usual dose range Is 25 10 150 mg b.l.d. or t.l.d. Amaximum daily dose of 450 mg

caplopril should notbe exceeded.

For patients vlith severe hypertension (e.g., accelerated or malignant hypertension), when temporary discontinualion of curren!

antihypertensive therapy Is not practical or desirable, or when prompt titration to more normotensive blood pressure levels ls Indicaled,

c;liureUc should be continued but other current antihypertensive medication slopped and captopril dosage promptly Initialed at 25 mgb.l.d.

orUd., underdose medical supervision.

When necessitated bylhe patient"s clinical condition, the dallydose of captopril maybeincreased every 24 hours or less undercontinuous

medical supervision until asatisfaclo/y blood pressure response is oblalned or the maximum dose of captoprills reached. In !his regimen.

addition of amore potent diureUc, e.g., furosemide, may alsobe Indicated.

Bela-blockers mayalso be used inconjuncUon with caplopril therapy (see PRECAUTIONS: Drug Interactions), butthe effecls of the two

drugs are less than additive.

Heart Failure -Initiation ollherapv requiles consideration of recent diuretic therapy and the possibility of severe salVvolume depletion. In

patients with either normal or low blood pressure, who have been vigorously lrealed with diuretics and who may be hyponalremic and/or

hypoVolemic, aslarting dose of 6.25 or 12.5mg l.i.d. may minimize the magnitude or duration of the hypotensive effect (see WARNINGS:

Hypotension); for lhese patients, titration 10 the usual daily dosagecan then occur within the next several days.

For most patients the usual initial daily dosage Is 25 mg ti.d, After adose of 50 mg t.l,d. is reached, further Increases in dosage should be

delayed, whete possible, for at least two weeks to determine Ha satisfactory response occurs. Most patients studied have had a

sallsfactol)" clinical improvementat50or 100mgIJ.d.Amaximumdaily dose of 450mg of captopril should nol be exceeded.

Captopril shouW generally be used In conjunction with adiuretic and digitalis. Captopriltherapymust be initiated under vel)" close medical

supervision.

Left Ventrlcular Dysfunction After Myocardlallnfarctlon - The recommended dose for long-term use In patients following amyocardial

infarction is atarget maintenance dO!je of 50mgU.d.

Therapy may be Initiated as early as three days following amyocardial infarction. After asingle dose of 6.25l"ng, caploprillablets therapy

should belnltialed at 12.5 mg t.i.d. Captoprillablets should then be Increased to 25 mg t.l.d. during Ihe next several days and to atarget

dose 0150 mg tid. over the next several weeks as toleraled (seeClINICALPHARMACOLOGY).

CaplopriJ tablets maybe used in patlenls treated wHh other posl·myocardiallnfarcllon therapies, e.g.lhrombolyllcs, aspirin, beta blockers.

Dla belle Nephropathy:The recommended dose of Captoprll tablets for long term use 10 treat diabeticnephropathyis 25mgl.l.d.

Other antihypertensives such as diuretics, bela blockers, centrally acllng agents orvasodilalors may be used in conjuctlon with Captopril

lablelsit additiqnal therapyIS reqUired 10 further lowerblood pressure.

Dosage Adjustment In Renal Impairment - Because captopril is excreled primarily by the kidneys, excretion rates are reduced in

patients with Impaired renal function.

These paUenls will take longer. 10 reach steady-state cap!oprtllevels and will reach higher steady·stale levels for agiven daily dose Ihan

patients with normal renal function. Therefore, these patientsmayrespond to smaller or less frequent doses.

AcCordingly, for patlents with significant renal Impairment, Initial dailY dosage of caplopril should be reduced, and smaller Incremenls

utilized fortltration, Yihich should be quite"slow (one-Io two-week intelVals). After the desired therapeutic effect has been achIeved, the

dose should be slowlyback titrated to determine the minimal effective dose. When concomitant diurellc-therapy Is required, aloOp diuretic

(e.g., furosemide), ratherlhan athiazidediuretlp, Is preferred"ln palienlswlthsevere renal Impairment. (Sea WARNINGS: Anaphylactoid

reactions during membrane exposure B'nd PRECAUTIONS: Hemodialysis.)

Captopril Tablets USP

12.5 mg tabtets in blisterpacks 30 (NDC 0615-4519-39).

25 mg tablets In blisterpacks 30(NDC 0615-4520-39).

50 mg tablets In blisterpacks 30 (NDC 0615-4521-39).

Bottle contains desiccant.

The 12.5 mg tablet is white, flat bevelled-edge round with a bisect bar on one side and W;902 on the other side; the 25mg Captopril tablet is a white, flat vevelled-edge round with a quadrisect bar on one side and W;903 on the other side; the 50mg Captopril tablet is a white, flat vevelled-edge round with a bisect bar on one side and W;904 on the other side.

All caplopril tablets are while and may exhlblt a slight sulfurous odor.

Dispensein a light container as defined in the USP.

Storage

Do nol store above 30"C (86"F) Keep bottles tIghtly closed (protect from moisture).

Manufaclured by:

Wockhardt Limited

Mumbal, India.

Distributed by:

Wockhardt USA LLC.

20 Walervlew Blvd.

Parsippany, NJ 07054

USA.

Rev.220709

Captopril Tablets,

USP 12.5 mg

Captopril  Tablets,

USP 25mg

Captopril Tablets,

USP 50mg