Captopril

(kap' toe pril)

PCI - Contraindicated in pregnancy

LCaution when used during lactation - Caution when used during lactation

Molecule Info

 
 WARNING

FETAL TOXICITY
• When pregnancy is detected, discontinue Captopril as soon as possible.
• Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. 

Indication(s) & Dosage

Captopril is indicated for the treatment of hypertension.
In using Captopril, consideration should be given to the risk of neutropenia/agranulocytosis.

Captopril may be used as initial therapy for patients with normal renal function, in whom the risk is relatively low. In patients with impaired renal function, 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.
Captopril is effective alone and in combination with other antihypertensive agents, especially thiazide-type diuretics. The blood pressure lowering effects of captopril and thiazides are approximately additive.
Heart Failure: Captopril is indicated in the treatment of congestive heart failure usually in combination with diuretics and digitalis. The beneficial effect of captopril in heart failure does not require the presence of digitalis, however, most controlled clinical trial experience with captopril has been in patients receiving digitalis, as well as diuretic treatment.

Left Ventricular Dysfunction After Myocardial Infarction: Captopril is indicated to improve survival following myocardial infarction in clinically stable patients with left ventricular
dysfunction manifested as an ejection fraction ≤40% and to reduce the incidence of overt heart failure and subsequent hospitalizations for congestive heart failure in these patients.
Diabetic Nephropathy: Captopril is indicated for the treatment of diabetic nephropathy (proteinuria >500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy. Captopril decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis). In considering use of Captopril, it should be noted that in controlled trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. In addition, ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients.

Hypertension
Adult: Initially, 12.5 mg bid or 6.25 mg bid in combination with a diuretic, at bedtime to avoid precipitous fall in BP, gradually increased at 2-4-wk intervals according to response. Maintenance: 25-50 mg bid. Max: 50 mg tid. 
Child: Neonate: Test dose: 10-50 mcg/kg (for neonates <37 wk postmenstrual age: 10 mcg/kg), monitor BP for 1-2 hr; if tolerated give 10-50 mcg/kg 2-3 times daily, increased if needed. Max: 2 mg/kg daily in divided doses (for neonates <37 wk postmenstrual age: 300 mcg/kg daily in divided doses). 1 mth-12 yr: Test dose: 100 mcg/kg (max: 6.25 mg), monitor BP for 1-2 hr; if tolerated give 100-300 mcg/kg 2-3 times daily, increased if needed. Max: 6 mg/kg daily in divided doses (for 1-12 mth: Max: 4 mg/kg daily in divided doses). 12-18 yr: Test dose: 100 mcg/kg or 6.25 mg, monitor BP for 1-2 hr; if tolerated give 12.5-25 mg 2-3 times daily, increased if needed. Max: 150 mg daily in divided doses. 
Elderly: Initially, 6.25 mg bid.

CrCl (ml/min) Dosage Recommendation
21-40 Initially, 25 mg daily. Max: 100 mg daily.
10-20 Initially, 12.5 mg daily. Max: 75 mg daily.
<10 Initially, 6.25 mg daily. Max: 37.5 mg daily.

Oral
Heart failure
Adult: Initially, 6.25-12.5 mg bid-tid. Maintenance: 25 mg bid-tid. Max: 50 mg tid. 
Child: Neonate: Test dose: 10-50 mcg/kg (for neonates <37 wk postmenstrual age: 10 mcg/kg), monitor BP for 1-2 hr; if tolerated give 10-50 mcg/kg 2-3 times daily, increased if needed. Max: 2 mg/kg daily in divided doses (for neonates <37 wk postmenstrual age: 300 mcg/kg daily in divided doses). 1 mth-12 yr: Test dose: 100 mcg/kg (max: 6.25 mg), monitor BP for 1-2 hr; if tolerated give 100-300 mcg/kg 2-3 times daily, increased if needed. Max: 6 mg/kg daily in divided doses (for 1-12 mth: Max: 4 mg/kg daily in divided doses). 12-18 yr: Test dose: 100 mcg/kg or 6.25 mg, monitor BP for 1-2 hr; if tolerated give 12.5-25 mg 2-3 times daily, increased if needed. Max: 150 mg daily in divided doses.
CrCl (ml/min) Dosage Recommendation
21-40 Initially, 25 mg daily. Max: 100 mg daily.
10-20 Initially, 12.5 mg daily. Max: 75 mg daily.
<10 Initially, 6.25 mg daily. Max: 37.5 mg daily.

Oral
Post myocardial infarction
Adult: May be started 3 days after MI. Initially, 6.25 mg/day increased after several wk to 150 mg daily in divided doses if tolerated.
CrCl (ml/min) Dosage Recommendation
21-40 Initially, 25 mg daily. Max: 100 mg daily.
10-20 Initially, 12.5 mg daily. Max: 75 mg daily.
<10 Initially, 6.25 mg daily. Max: 37.5 mg daily.

Oral
Diabetic nephropathy
Adult: Proteinuria >500 mg per 24 hr (in patients with Type 1 diabetes mellitus and retinopathy): 25 mg tid. May be taken with other anti-hypertensives if patient requires further lowering of BP. 
Child: Neonate: Test dose: 10-50 mcg/kg (for neonates <37 wk postmenstrual age: 10 mcg/kg), monitor BP for 1-2 hr; if tolerated give 10-50 mcg/kg 2-3 times daily, increased if needed. Max: 2 mg/kg daily in divided doses (for neonates <37 wk postmenstrual age: 300 mcg/kg daily in divided doses). 1 mth-12 yr: Test dose: 100 mcg/kg (max: 6.25 mg), monitor BP for 1-2 hr; if tolerated give 100-300 mcg/kg 2-3 times daily, increased if needed. Max: 6 mg/kg daily in divided doses (for 1-12 mth: Max: 4 mg/kg daily in divided doses). 12-18 yr: Test dose: 100 mcg/kg or 6.25 mg, monitor BP for 1-2 hr; if tolerated give 12.5-25 mg 2-3 times daily, increased if needed. Max: 150 mg daily in divided doses.
CrCl (ml/min) Dosage Recommendation
21-40 Initially, 25 mg daily. Max: 100 mg daily.
10-20 Initially, 12.5 mg daily. Max: 75 mg daily.
<10 Initially, 6.25 mg daily. Max: 37.5 mg daily.

Special Populations: Patients with severe renal impairment: CrCl <30 mL/min: Initially, 12.5 mg bid.
Administration Should be taken on an empty stomach. Take on an empty stomach 1 hr before or 2 hr after meals.
Overdosage Treatment includes correction of hypotension. Volume expansion with an IV infusion of normal saline may be used for restoration of BP.
Contraindications Known hypersensitivity to the drug. Bilateral renal artery stenosis, hereditary angioedema; renal impairment; pregnancy.
Special Precautions Patients on diuretics or with sodium depletion should discontinue diuretics or increase sodium intake prior to initiation of therapy. Renal impairment, SLE and other autoimmune collagen disorders and during concurrent use of immunosuppressant or leucopenic drugs, monitor WBC count and urinary protein before and during therapy. Lactation. Porphyria. Severe CHF.
Adverse Drug Reaction(s) Hypotension, tachycardia, chest pain, palpitations, pruritus, hyperkalaemia. Proteinuria; angioedema, skin rashes; taste disturbance, nonproductive cough, headache.
Potentially Fatal: Neutropenia, usually occurs within 3 mth of starting therapy especially in patients with renal dysfunction or collagen diseases. Hyperkalaemia. Anaphylactic reactions.
Drug Interactions Concurrent treatment with diuretics increases the hypotensive action of ACE inhibitors hence, starting dose must be kept low.
Potentially Fatal: Risk of bone marrow depression increased with concomitant therapy with immunosuppressive drugs. Hyperkalaemia may result if used along with potassium supplements and potassium-sparing diuretics especially if renal function is impaired. Probenecid delays excretion of captopril thereby increasing blood levels. Analgesic and respiratory depression of morphine may be accentuated by captopril. NSAIDs may result in further deterioration of renal function.
Food Interaction Concurrent admin with food may reduce serum levels of captopril. Avoid dong quai (if using for hypertension), ephedra, yohimbe, ginseng (may worsen hypertension) and garlic (may increase antihypertensive effect).
Lab Interference False-positive test for urinary nitrites and acetone. Increased BUN, creatinine and potassium.
Pregnancy Category (FDA) and use in Specific Population

Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Nursing Mothers

Concentrations of captopril in human milk are approximately one percent of those in maternal blood. Because of the potential for serious adverse reactions in nursing infants from captopril, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of Captopril to the mother.

Pediatric Use

Neonates with a history of in utero exposure to Captopril.
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. 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 children. Peritoneal dialysis is not effective for removing captopril; there is no information concerning exchange transfusion for removing captopril form the general circulation.

Safety and effectiveness in pediatric patients have not been established. There is limited experience reported in the literature with the use of captopril in the pediatric population; dosage, on a weight basis, was generally reported to be comparable to or less than that used in adults. Infants, especially newborns, may be more susceptible to the adverse hemodynamic effects of captopril. Excessive, prolonged and unpredictable decreases in blood pressure and associated complications, including oliguria and seizures, have been reported. Captopril should be used in pediatric patients only if other measures for controlling blood pressure have not been effective.

Storage Store below 30°C
Pharmacology

Mechanism of Action
The mechanism of action of Captopril has not yet been fully elucidated. Its beneficial effects in hypertension and heart failure appear to result primarily from suppression of the renin­angiotensin-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. This inhibition has been demonstrated in both healthy human subjects and in animals by showing that the elevation of blood pressure caused by exogenously administered angiotensin I was attenuated or abolished by captopril. In animal studies, captopril did not alter the pressor responses to a number of other agents, including angiotensin II and norepinephrine, indicating specificity of action. 

ACE is identical to ''bradykininase'', and Captopril may also interfere with the degradation of the vasodepressor peptide, bradykinin. Increased concentrations of bradykinin or prostaglandin E2 may also have a role in the therapeutic effect of Captopril. 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.

Pharmacokinetics
After 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 percent; captopril therefore should be given one hour before meals. Based on carbon-14 labeling, average minimal absorption is approximately 75 percent. In a 24­ hour period, over 95 percent of the absorbed dose is eliminated in the urine; 40 to 50 percent is unchanged drug; most of the remainder is the disulfide dimer of captopril and captopril-cysteine disulfide. Approximately 25 to 30 percent of the circulating drug is bound to plasma proteins. The apparent
elimination half-life for total radioactivity in blood is probably less than 3 hours. An accurate determination of half-life of unchanged captopril is not, at present, possible, but it is probably less than 2 hours. In patients with renal impairment, however, retention of captopril occurs.

Pharmacodynamics
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. Reductions of blood pressure are usually maximal 60 to 90 minutes after oral administration of an individual dose of Captopril. The duration of effect is 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 are additive. In contrast, captopril and beta-blockers have a less than additive effect. 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.
In patients with heart failure, significantly decreased peripheral (systemic vascular) resistance and blood pressure (afterload), reduced pulmonary capillary wedge pressure (preload) and pulmonary vascular resistance, increased cardiac output, and increased exercise tolerance time (ETT) have been demonstrated. These hemodynamic and clinical effects occur after the first dose and appear to persist for the duration of therapy. Placebo controlled studies of 12 weeks duration in patients who did not respond adequately to diuretics and digitalis show no tolerance to beneficial effects on ETT; open studies, with exposure up to 18 months in some cases, also indicate that ETT benefit is maintained. Clinical improvement has been observed in some patients where acute hemodynamic effects were minimal. 

The Survival and Ventricular Enlargement (SAVE) study was a multicenter, randomized, double-blind, placebo-controlled trial conducted in 2,231 patients (age 21-79 years) who
survived the acute phase of myocardial infarction and did not have active ischemia. Patients had left ventricular dysfunction (LVD), defined as a resting left ventricular ejection fraction ≤40%, but at the time of randomization were not sufficiently symptomatic to require ACE inhibitor therapy for heart failure. About half of the patients had symptoms of heart failure in the past.
Patients were given a test dose of 6.25 mg oral Captopril and were randomized within 3-16 days post-infarction to receive either Captopril or placebo in addition to conventional therapy. Captopril was initiated at 6.25 mg or 12.5 mg t.i.d. and after two weeks titrated to a target maintenance dose of 50 mg t.i.d. About 80% of patients were receiving the target dose at the end of the study. Patients were followed for a minimum of two years and for up to five years, with an average follow-up of 3.5 years. Baseline blood pressure was 113/70 mmHg and 112/70 mmHg for the placebo and Captopril groups, respectively. Blood pressure increased slightly in both treatment groups during the study
and was somewhat lower in the Captopril group (119/74 vs. 125/77 mmHg at 1 yr). Therapy with Captopril improved long-term survival and clinical outcomes compared to
placebo. The risk reduction for all cause mortality was 19% (P=0.02) and for cardiovascular death was 21% (P=0.014). Captopril treated subjects had 22% (P=0.034) fewer first
hospitalizations for heart failure. Compared to placebo, 22% fewer patients receiving captopril developed symptoms of overt heart failure. There was no significant difference between groups in total hospitalizations for all cause (2056 placebo; 2036 captopril).
Captopril was well tolerated in the presence of other therapies such as aspirin, beta blockers, nitrates, vasodilators, calcium antagonists and diuretics. In a multicenter, double-blind, placebo controlled trial, 409 patients, age 18-49 of either gender, with or without hypertension, with type I (juvenile type, onset before age 30) insulin-dependent
diabetes mellitus, retinopathy, proteinuria ≥500 mg per day and serum creatinine ≤ 2.5 mg/dL, were randomized to placebo or Captopril (25 mg t.i.d.) and followed for up to 4.8 years (median 3 years). To achieve blood pressure control, additional antihypertensive agents (diuretics, beta blockers, centrally acting agents or vasodilators) were added as needed for patients in both groups.
The Captopril group had a 51% reduction in risk of doubling of serum creatinine (P<0.01) and a 51% reduction in risk for the combined endpoint of end-stage renal disease (dialysis or transplantation) or death (P<0.01). Captopril treatment resulted in a 30% reduction in urine protein excretion within the first 3 months (P<0.05), which was maintained throughout the trial. The Captopril group had somewhat better blood pressure control than the placebo group, but the effects of Captopril on renal function were greater than would be expected from the group differences in blood pressure reduction alone. Captopril was well tolerated in this patient population. 

In two multicenter, double-blind, placebo controlled studies, a total of 235 normotensive patients with insulin-dependent diabetes mellitus, retinopathy and microalbuminuria (20-200 µg/min) were randomized to placebo or Captopril (50 mg b.i.d.) and followed for up to 2 years. Captopril delayed the progression to overt nephropathy (proteinuria ≥ 500 mg/day) in both studies (risk reduction 67% to 76%; P<0.05). Captopril also reduced the albumin excretion rate. However, the long term clinical benefit of reducing the progression from microalbuminuria to proteinuria has not been established. Studies in rats and cats indicate that Captopril does not cross the blood-brain barrier to any
significant extent. 

Captopril competitively inhibits the conversion of angiotensin I (ATI) to angiotensin II (ATII), thus resulting in reduced ATII levels and aldosterone secretion. It also increases plasma renin activity and bradykinin levels. Reduction of ATII leads to decreased sodium and water retention. By these mechanisms, captopril produces a hypotensive effect and a beneficial effect in congestive heart failure.
Absorption: 60-75% absorbed from the GI tract (oral); peak plasma concentrations after 1 hr. Absorption may be reduced in the presence of food.
Distribution: Protein-binding: 30%; crosses the placenta and enters breast milk at about 1% of maternal blood concentrations.
Excretion: Via urine (40-50% as unchanged, the rest as disulfide and other metabolites); 2-3 hr (elimination half-life), may be increased in renal impairment. Removed by haemodialysis.

ATC Classification C09AA01 - captopril; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.

Brand Info


Total Products : 7       
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
ACETOR Drug International Ltd Captopril 25mg Tablet 100's: 300.00 MRP
ANGITEN IBN SINA Pharmaceutical Industry Ltd. Captopril 25mg Tablet 100's: 325.00 IP
CAPOTRIL Alco Pharma Ltd Captopril 25mg Tablet 40's: 120.00 MRP
CARDOPRIL 25 Beximco Pharmaceuticals Ltd Captopril USP 25mg Tablet 100's: 301.00 MRP
CARDOPRIL 50 Beximco Pharmaceuticals Ltd Captopril USP 50mg Tablet 100's: 602.00 MRP
CATOPIL Zenith Pharmaceuticals Ltd. Captopril USP 12.5 & 25mg Tablet 100'seach: 175.00 & 300.00 MRP
TOPRIL Jayson Pharmaceuticals Ltd. Captopril 25mg Tablet 50's: 139.50 IP

Gen. MedInfo

IMPORTANT WARNING:

Do not take captopril if you are pregnant or breast-feeding. If you become pregnant while taking captopril, call your doctor immediately.

 

Purpose of this medication

Captopril is used to treat high blood pressure and heart failure. It decreases certain chemicals that tighten the blood vessels, so blood flows more smoothly and the heart can pump blood more efficiently.

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

How this medicine should be used?

Captopril comes as a tablet to take by mouth. It is usually taken two or three times a day on an empty stomach, 1 hour before or 2 hours after a meal. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take captopril exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Captopril controls high blood pressure and heart failure but does not cure them.

Continue to take captopril even if you feel well. Do not stop taking captopril without talking to your doctor.

Special precautions to follow

Before taking captopril,

  • tell your doctor if you are allergic to captopril or any other drugs.
  • tell your doctor if you have diabetes (high blood sugar) and you are taking aliskiren. Your doctor will probably tell you not to take captopril if you have diabetes and you are also taking aliskiren.
  • tell your doctor what prescription and nonprescription medications you are taking, especially diuretics, lithium, other medications for high blood pressure, potassium supplements, and vitamins.
  • tell your doctor if you have or have ever had heart or kidney disease or diabetes.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking captopril.

Special dietary instructions to follow

Talk to your doctor before using salt substitutes containing potassium. If your doctor prescribes a low-salt or low-sodium diet, follow these instructions carefully.

Missing dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Possible side effects

Captopril may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • dizziness or lightheadedness
  • salty or metallic taste, or decreased ability to taste
  • cough
  • sore throat
  • fever
  • mouth sores
  • unusual bruising
  • fast heartbeat
  • excessive tiredness
  • chest pain
  • swelling of the face, eyes, lips, tongue, arms, or legs
  • difficulty breathing or swallowing
  • fainting
  • rash

If you experience any of the following symptoms, call your doctor immediately:

  • chest pain
  • swelling of the face, eyes, lips, tongue, arms, or legs
  • difficulty breathing or swallowing
  • fainting
  • rash

What storage conditions are needed for this medicine?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

Ref: U.S. Natl. Library of Medicine

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