Blocordil (Tablets) Instructions for Use

ATC Code

C09AA01 (Captopril)

Active Substance

Captopril (Rec.INN registered by WHO)

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE blocker

Pharmacological Action

Antihypertensive agent, ACE inhibitor. The mechanism of the antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II (which has a pronounced vasoconstrictive effect and stimulates the secretion of aldosterone in the adrenal cortex). Furthermore, Captopril appears to affect the kinin-kallikrein system, preventing the breakdown of bradykinin.

The hypotensive effect is independent of plasma renin activity; a decrease in blood pressure is noted with normal and even reduced hormone concentration, which is due to the effect on the tissue renin-angiotensin-aldosterone system (RAAS). It increases coronary and renal blood flow.

Due to its vasodilatory action, it reduces total peripheral vascular resistance (afterload), pulmonary capillary wedge pressure (preload) and resistance in the pulmonary vessels; it increases cardiac output and exercise tolerance.

With long-term use, it reduces the severity of left ventricular myocardial hypertrophy, prevents the progression of heart failure and slows the development of left ventricular dilation. It helps to reduce sodium levels in patients with chronic heart failure. It dilates arteries to a greater extent than veins. It improves blood supply to the ischemic myocardium. It reduces platelet aggregation.

It lowers the tone of the efferent glomerular arterioles of the kidneys, improving intraglomerular hemodynamics, and prevents the development of diabetic nephropathy.

Pharmacokinetics

After oral administration, at least 75% is rapidly absorbed from the gastrointestinal tract. Simultaneous food intake reduces absorption by 30-40%. C_max in blood plasma is reached within 30-90 minutes. Protein binding, predominantly with albumin, is 25-30%. It is excreted in breast milk.

It is metabolized in the liver to form captopril disulfide dimer and captopril-cysteine disulfide. The metabolites are pharmacologically inactive.

T_1/2 is less than 3 hours and increases in renal failure (3.5-32 hours). More than 95% is excreted by the kidneys, 40-50% unchanged, the remainder as metabolites.

It accumulates in chronic renal failure.

Indications

Arterial hypertension (including renovascular), chronic heart failure (as part of combination therapy), left ventricular dysfunction after myocardial infarction in clinically stable patients. Diabetic nephropathy in type 1 diabetes mellitus (with albuminuria greater than 30 mg/day).

ICD codes

Dosage Regimen

Initiate treatment for arterial hypertension at 6.25 mg to 12.5 mg orally two to three times daily.

For chronic heart failure, start at 6.25 mg to 12.5 mg three times daily as part of a combination therapy regimen.

In patients with post-myocardial infarction left ventricular dysfunction, begin with a low dose once the patient is clinically stable.

Titrate the dose upward at intervals of one to two weeks if the therapeutic response is insufficient.

Increase the dose gradually to a typical maintenance dose of 25 mg to 50 mg administered three times daily.

Do not exceed the maximum daily dose of 150 mg.

Adjust the dosage in patients with impaired renal function; reduce the daily dose and consider extending the dosing interval.

Administer doses one hour before meals for optimal absorption, as food can significantly reduce bioavailability.

Monitor blood pressure closely following the initial dose and after each dosage increase to assess for excessive hypotensive effect.

Exercise particular caution during initiation and titration in patients who are volume-depleted, are on diuretic therapy, or have severe heart failure.

Adverse Reactions

From the central and peripheral nervous system: dizziness, headache, feeling of fatigue, asthenia, paresthesia.

From the cardiovascular system: orthostatic hypotension; rarely – tachycardia.

From the digestive system: nausea, loss of appetite, taste disturbance; rarely – abdominal pain, diarrhea or constipation, increased activity of liver transaminases, hyperbilirubinemia; signs of hepatocellular damage (hepatitis); in some cases – cholestasis; in isolated cases – pancreatitis.

From the hematopoietic system: rarely – neutropenia, anemia, thrombocytopenia; very rarely in patients with autoimmune diseases – agranulocytosis.

From metabolism: hyperkalemia, acidosis.

From the urinary system: proteinuria, impaired renal function (increased blood urea and creatinine concentrations).

From the respiratory system: dry cough.

Allergic reactions: skin rash; rarely – angioedema, bronchospasm, serum sickness, lymphadenopathy; in some cases – appearance of antinuclear antibodies in the blood.

Contraindications

Pregnancy, lactation period, age under 18 years, hypersensitivity to captopril and other ACE inhibitors.

Use in Pregnancy and Lactation

It should be borne in mind that the use of captopril in the second and third trimesters of pregnancy can cause developmental disorders and fetal death. If pregnancy is confirmed, Captopril should be discontinued immediately.

Captopril is excreted in breast milk. If it is necessary to use it during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Should be used with caution in hepatic insufficiency.

Use in Renal Impairment

Should be used with caution in patients after kidney transplantation, renal failure.

In case of impaired renal function, the daily dose should be reduced.

Concomitant use of potassium-sparing diuretics and potassium preparations should be avoided in patients with renal impairment.

Pediatric Use

Contraindicated under 18 years of age. The use of captopril in children is possible only if other drugs are ineffective.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

Should be used with caution in cases of history of angioedema during therapy with ACE inhibitors, hereditary or idiopathic angioedema, with aortic stenosis, cerebro- and cardiovascular diseases (including cerebrovascular insufficiency, coronary artery disease, coronary insufficiency), severe autoimmune connective tissue diseases (including systemic lupus erythematosus, scleroderma), with bone marrow depression, with diabetes mellitus, hyperkalemia, bilateral renal artery stenosis, stenosis of the artery of a single kidney, condition after kidney transplantation, renal and/or hepatic insufficiency, against the background of a sodium-restricted diet, conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting), in elderly patients.

In patients with chronic heart failure, Captopril should be used under careful medical supervision.

Arterial hypotension occurring during surgery while taking captopril is corrected by volume replacement.

Concomitant use of potassium-sparing diuretics and potassium preparations should be avoided, especially in patients with renal impairment and diabetes mellitus.

When taking captopril, a false-positive reaction may be observed in the urine test for acetone.

The use of captopril in children is possible only if other drugs are ineffective.

Effect on ability to drive vehicles and operate machinery

Caution is required when driving vehicles or performing other work that requires increased attention, because dizziness is possible, especially after the initial dose of captopril.

Drug Interactions

With simultaneous use with immunosuppressants, cytostatics, the risk of leukopenia increases.

With simultaneous use with potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop (especially in patients with impaired renal function), because ACE inhibitors reduce aldosterone content, which leads to potassium retention in the body against the background of limited potassium excretion or its additional intake.

With simultaneous use of ACE inhibitors and NSAIDs, the risk of impaired renal function increases; hyperkalemia is rarely observed.

With simultaneous use with “loop” diuretics or thiazide diuretics, pronounced arterial hypotension is possible, especially after taking the first dose of the diuretic, apparently due to hypovolemia, which leads to a transient increase in the antihypertensive effect of captopril. There is a risk of hypokalemia. Increased risk of impaired renal function.

With simultaneous use with anesthetic agents, severe arterial hypotension is possible.

With simultaneous use with azathioprine, anemia may develop, which is due to inhibition of erythropoietin activity under the influence of ACE inhibitors and azathioprine. Cases of leukopenia have been described, which may be associated with additive inhibition of bone marrow function.

With simultaneous use with allopurinol, the risk of hematological disorders increases; cases of severe hypersensitivity reactions, including Stevens-Johnson syndrome, have been described.

With simultaneous use of aluminum hydroxide, magnesium hydroxide, magnesium carbonate, the bioavailability of captopril decreases.

Acetylsalicylic acid in high doses may reduce the antihypertensive effect of captopril. It has not been definitively established whether acetylsalicylic acid reduces the therapeutic efficacy of ACE inhibitors in patients with coronary artery disease and heart failure. The nature of this interaction depends on the course of the disease. Acetylsalicylic acid, by inhibiting COX and prostaglandin synthesis, can cause vasoconstriction, which leads to a decrease in cardiac output and worsening of the condition of patients with heart failure receiving ACE inhibitors.

There are reports of an increase in the plasma concentration of digoxin with simultaneous use of captopril with digoxin. The risk of drug interaction is increased in patients with impaired renal function.

With simultaneous use with indomethacin, ibuprofen, the antihypertensive effect of captopril decreases, apparently due to inhibition of prostaglandin synthesis under the influence of NSAIDs (which are believed to play a certain role in the development of the hypotensive effect of ACE inhibitors).

With simultaneous use with insulins, hypoglycemic agents derivatives of sulfonylurea, hypoglycemia may develop due to increased glucose tolerance.

With simultaneous use of ACE inhibitors and interleukin-3, there is a risk of arterial hypotension.

With simultaneous use with interferon alfa-2a or interferon beta, cases of severe granulocytopenia have been described.

When switching from clonidine to Captopril, the antihypertensive effect of the latter develops gradually. In case of sudden withdrawal of clonidine in patients receiving Captopril, a sharp increase in blood pressure is possible.

With simultaneous use of lithium carbonate, the concentration of lithium in the blood serum increases, accompanied by symptoms of intoxication.

With simultaneous use with minoxidil, sodium nitroprusside, the antihypertensive effect is enhanced.

With simultaneous use with orlistat, a decrease in the effectiveness of captopril is possible, which can lead to an increase in blood pressure, hypertensive crisis, a case of cerebral hemorrhage has been described.

With simultaneous use of ACE inhibitors with pergolide, an enhancement of the antihypertensive effect is possible.

With simultaneous use with probenecid, the renal clearance of captopril decreases.

With simultaneous use with procainamide, the risk of leukopenia may increase.

With simultaneous use with trimethoprim, there is a risk of hyperkalemia, especially in patients with impaired renal function.

With simultaneous use with chlorpromazine, there is a risk of orthostatic hypotension.

With simultaneous use with cyclosporine, there are reports of the development of acute renal failure, oliguria.

It is believed that a decrease in the effectiveness of antihypertensive agents is possible with simultaneous use with erythropoietins.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.