Veltokor (Tablets) Instructions for Use

Marketing Authorization Holder

Bright Way, LLC (Russia)

Manufactured By

Velpharm, LLC (Russia)

ATC Code

C09AA01 (Captopril)

Active Substance

Captopril (Rec.INN registered by WHO)

Dosage Forms

	Veltokor	Tablets 25 mg: 7, 10, 14, 20, 21, 28, 30, 35, 40, 42, 49, 50, 56, 60, 63, 70, 80, 84, 90, 98, 100, 112, 126 or 140 pcs.
		Tablets 50 mg: 7, 10, 14, 20, 21, 28, 30, 35, 40, 42, 49, 50, 56, 60, 63, 70, 80, 84, 90, 98, 100, 112, 126 or 140 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat-cylindrical, with a score and a bevel, with a characteristic odor; the presence of “marbling” is allowed.

Excipients: lactose monohydrate (milk sugar), microcrystalline cellulose (type 102), magnesium stearate, talc, colloidal silicon dioxide (aerosil), crospovidone (kollidon CL-M, kollidon CL).

7 pcs. – blister packs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) – cardboard packs.
10 pcs. – blister packs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) – cardboard packs.
14 pcs. – blister packs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) – cardboard packs.
7 pcs. – jars (1) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
14 pcs. – jars (1) – cardboard packs.
20 pcs. – jars (1) – cardboard packs.
21 pcs. – jars (1) – cardboard packs.
28 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
35 pcs. – jars (1) – cardboard packs.
40 pcs. – jars (1) – cardboard packs.
42 pcs. – jars (1) – cardboard packs.
49 pcs. – jars (1) – cardboard packs.
50 pcs. – jars (1) – cardboard packs.
56 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
63 pcs. – jars (1) – cardboard packs.
70 pcs. – jars (1) – cardboard packs.
80 pcs. – jars (1) – cardboard packs.
84 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
98 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.
112 pcs. – jars (1) – cardboard packs.
126 pcs. – jars (1) – cardboard packs.
140 pcs. – jars (1) – cardboard packs.

Tablets white or almost white, round, flat-cylindrical, with a score and a bevel, with a characteristic odor; the presence of “marbling” is allowed.

Excipients: lactose monohydrate (milk sugar), microcrystalline cellulose (type 102), magnesium stearate, talc, colloidal silicon dioxide (aerosil), crospovidone (kollidon CL-M, kollidon CL).

7 pcs. – blister packs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) – cardboard packs.
10 pcs. – blister packs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) – cardboard packs.
14 pcs. – blister packs (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) – cardboard packs.
7 pcs. – jars (1) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
14 pcs. – jars (1) – cardboard packs.
20 pcs. – jars (1) – cardboard packs.
21 pcs. – jars (1) – cardboard packs.
28 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
35 pcs. – jars (1) – cardboard packs.
40 pcs. – jars (1) – cardboard packs.
42 pcs. – jars (1) – cardboard packs.
49 pcs. – jars (1) – cardboard packs.
50 pcs. – jars (1) – cardboard packs.
56 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
63 pcs. – jars (1) – cardboard packs.
70 pcs. – jars (1) – cardboard packs.
80 pcs. – jars (1) – cardboard packs.
84 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
98 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.
112 pcs. – jars (1) – cardboard packs.
126 pcs. – jars (1) – cardboard packs.
140 pcs. – jars (1) – cardboard packs.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

Agents acting on the renin-angiotensin system; angiotensin-converting enzyme (ACE) inhibitors

Pharmacological Action

Antihypertensive agent, ACE inhibitor. The mechanism of 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). In addition, Captopril appears to affect the kinin-kallikrein system by preventing the breakdown of bradykinin. The hypotensive effect does not depend on plasma renin activity; a decrease in blood pressure is noted at normal and even reduced hormone concentrations, which is due to the effect on the tissue RAAS. Increases coronary and renal blood flow.

Due to its vasodilating action, it reduces total peripheral vascular resistance (afterload), pulmonary capillary wedge pressure (preload) and resistance in the pulmonary vessels; 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 dilatation. Helps reduce sodium content in patients with chronic heart failure. Dilates arteries more than veins. Improves blood supply to the ischemic myocardium. Reduces platelet aggregation.

Lowers the tone of the efferent arterioles of the renal glomeruli, 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 after 30-90 min. Protein binding, predominantly with albumin, is 25-30%. Excreted in breast milk. Metabolized in the liver to form captopril disulfide dimer and captopril-cysteine disulfide. 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 rest in the form of metabolites.

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 more than 30 mg/day).

ICD codes

Dosage Regimen

Take the tablets orally, one hour before meals.

For arterial hypertension, initiate therapy at a starting dose of 6.25 mg to 12.5 mg, administered two to three times daily.

If the therapeutic response is insufficient, titrate the dose upward at intervals of one to two weeks.

The usual maintenance dose is 25 mg to 50 mg, taken two to three times per day.

Do not exceed a maximum daily dose of 150 mg.

For chronic heart failure, begin with a low dose of 6.25 mg to 12.5 mg three times daily, under close medical supervision.

Gradually increase the dose to a target maintenance level of 50 mg to 100 mg three times daily, as tolerated.

In patients with renal impairment, reduce the daily dose. Adjust the dosing interval or total daily dose based on creatinine clearance.

For patients with a creatinine clearance of 10-50 mL/min, administer 75% of the normal dose.

For patients with a creatinine clearance below 10 mL/min, administer 50% of the normal dose.

In geriatric patients, initiate therapy at the lower end of the dosing range due to potential age-related renal function decline.

Monitor blood pressure closely following the initial dose and after any dosage increase.

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 – the appearance of antinuclear antibodies in the blood.

Contraindications

Pregnancy, lactation, 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 II and III 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 during lactation, the issue of stopping 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 failure.

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

Use with caution in patients with a 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 solitary kidney, condition after kidney transplantation, renal and/or hepatic insufficiency, while on 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 failure and diabetes mellitus.

When taking captopril, a false-positive reaction may be observed when testing urine 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

When used concomitantly with immunosuppressants and cytostatics, the risk of leukopenia increases.

When used concomitantly 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.

When ACE inhibitors and NSAIDs are used concomitantly, the risk of impaired renal function increases; hyperkalemia is rarely observed.

When used concomitantly 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.

When used concomitantly with anesthetic agents, severe arterial hypotension is possible.

When used concomitantly with azathioprine, anemia may develop, which is due to suppression of erythropoietin activity under the influence of ACE inhibitors and azathioprine. Cases of leukopenia have been described, which may be associated with additive suppression of bone marrow function.

When used concomitantly with allopurinol, the risk of hematological disorders increases; cases of severe hypersensitivity reactions, including Stevens-Johnson syndrome, have been described.

When used concomitantly with 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 effectiveness 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 plasma digoxin concentration with concomitant use of captopril with digoxin. The risk of drug interaction is increased in patients with impaired renal function.

When used concomitantly with indomethacin, ibuprofen, the antihypertensive effect of captopril decreases, apparently due to inhibition of prostaglandin synthesis by NSAIDs (which are believed to play a role in the development of the hypotensive effect of ACE inhibitors).

When used concomitantly with insulins, sulfonylurea hypoglycemic agents, hypoglycemia may develop due to increased glucose tolerance.

When ACE inhibitors and interleukin-3 are used concomitantly, there is a risk of arterial hypotension.

When used concomitantly 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. If clonidine is abruptly discontinued in patients receiving Captopril, a sharp increase in blood pressure is possible.

When used concomitantly with lithium carbonate, the concentration of lithium in the blood serum increases, accompanied by symptoms of intoxication.

When used concomitantly with minoxidil, sodium nitroprusside, the antihypertensive effect is enhanced.

When used concomitantly with orlistat, a decrease in the effectiveness of captopril is possible, which can lead to increased blood pressure, hypertensive crisis, and a case of cerebral hemorrhage has been described.

When ACE inhibitors are used concomitantly with pergolide, an enhancement of the antihypertensive effect is possible.

When used concomitantly with probenecid, the renal clearance of captopril decreases.

When used concomitantly with procainamide, the risk of leukopenia may increase.

When used concomitantly with trimethoprim, there is a risk of hyperkalemia, especially in patients with impaired renal function.

When used concomitantly with chlorpromazine, there is a risk of orthostatic hypotension.

When used concomitantly with cyclosporine, there are reports of acute renal failure and oliguria.

It is believed that a decrease in the effectiveness of antihypertensive agents is possible when used concomitantly 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.