Captopril

Active material: Captopril
When ATH: C09AA01
CCF: ACE inhibitor
When CSF: 01.04.01.01
Manufacturer: M.J.BIOPHARM Pvt.Ltd. (India)

Pharmaceutical form, composition and packaging

Excipients: corn starch, lactose, magnesium stearate, talc.

10 PC. – packings Valium planimetric (2) – packs cardboard.

Excipients: corn starch, lactose, magnesium stearate, talc.

10 PC. – packings Valium planimetric (2) – packs cardboard.

Excipients: corn starch, lactose, magnesium stearate, talc.

10 PC. – packings Valium planimetric (2) – packs cardboard.

DESCRIPTION OF ACTIVE SUBSTANCES

Pharmacological action

Antihypertensive agents, ACE inhibitor. The mechanism of the antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate conversion of angiotensin I to angiotensin II (which has a strong vasoconstrictive effect and stimulates the secretion of aldosterone in the adrenal cortex). Besides, captopril, apparently, It affects the kallikrein-kinin system, preventing the breakdown of bradykinin. The hypotensive effect is independent of the plasma renin activity, blood pressure reduction noted in normal and even reduce the concentration of the hormone, due to exposure to the tissue renin-angiotensin system. Increases coronary and renal blood flow.

Thanks vasodilator action, reduces round (afterload), wedge pressure in the pulmonary capillaries (preload) and pulmonary vascular resistance; improves cardiac output and exercise tolerance. Prolonged use reduces the severity of left ventricular hypertrophy, It prevents the progression of heart failure and slows development of left ventricular dilatation. It helps reduce the sodium content in patients with chronic heart failure. It expands the artery to a greater extent, than veins. It improves blood flow to ischemic myocardium. It reduces platelet aggregation.

Lowers tone efferent arterioles of the glomeruli of the kidneys, intraglomerular improving hemodynamics, prevents the development of diabetic nephropathy.

Pharmacokinetics

After ingestion least 75% rapidly absorbed from the gastrointestinal tract. Simultaneous eating reduces the absorption in the 30-40%. C_max plasma levels achieved after 30-90 m. Protein binding, mostly to albumin, is 25-30%. Provided with breast milk. It is metabolized in the liver with the formation of a disulfide dimer of captopril and captopril-tsisteindisulfida. The metabolites are pharmacologically inactive.

T_1/2 is less than 3 hr and increased in renal failure (3.5-32 no). More 95% excreted by the kidneys, 40-50% in unchanged form, the rest of the – as metabolites.

In chronic renal failure koumouliruet.

Testimony

Arterial hypertension (incl. renovascular), congestive heart failure (in a combination therapy), left ventricular dysfunction after myocardial infarction in patients, are clinically stable. Diabetic nephropathy in diabetes mellitus type 1 (if albuminuria more 30 mg / day).

Dosage regimen

When administered an initial dose – by 6.25-12.5 mg 2-3 times / day. When little effect dose gradually increased to 25-50 mg 3 times / day. If the kidney function the daily dose should be reduced.

The maximum daily dose: 150 mg.

Side effect

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

Cardio-vascular system: orthostatic hypotension; rarely – tachycardia.

From the digestive system: nausea, decreased appetite, dysgeusia; rarely – stomach ache, diarrhea or constipation, increase in liver transaminases, giperʙiliruʙinemija; signs of hepatocellular damage (hepatitis); in some cases – cholestasis; in a few cases – pancreatitis.

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

Metabolism: hyperkalemia, Acidosis.

From the urinary system: proteinuria, impairment of renal function (increasing the concentration of urea and creatinine in the blood).

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, Age to 18 years, Hypersensitivity to captopril and other ACE inhibitors.

Pregnancy and lactation

It will be appreciated, that the use of captopril in II and III trimesters of pregnancy can cause developmental disorders and fetal death. When established pregnancy captopril should be lifted immediately.

Captopril is excreted in breast milk. If necessary, use during lactation should decide the issue of termination of breastfeeding.

Cautions

C care should be used when specifying a history of angioedema during therapy with ACE inhibitors, Hereditary or idiopathic angioedema, when aortic stenosis, cerebro- and cardiovascular diseases (incl. when cerebrovascular insufficiency, CHD, coronary insufficiency), severe autoimmune diseases of connective tissue (incl. SLE, scleroderma), the oppression of bone marrow hematopoiesis, for patients with diabetes, hyperkalemia, bilateral renal artery stenosis, stenosis of the artery to a solitary kidney, condition after kidney transplantation, kidney and / or liver failure, Background on sodium restricted diets, states, accompanied by a decrease in the bcc (incl. diarrhea, rvote), in elderly patients.

In patients with chronic heart failure captopril is used under close medical supervision.

Arises during surgery hypotension in patients receiving captopril eliminate the completion of the volume of liquid.

Avoid the simultaneous use of potassium-sparing diuretics and potassium preparations, especially in patients with renal insufficiency and diabetes.

When captopril may be a false positive reaction in the analysis of urine for acetone.

The use of captopril in children is possible only in case of failure of other drugs.

Effects on ability to drive vehicles and management mechanisms

Care should be taken when driving or performing other work, requiring greater attention, tk. dizziness, especially after the initial dose of captopril.

Drug Interactions

While the use of immunosuppressants, cytostatics increases the risk of leukopenia.

While the use of potassium-sparing diuretics (incl. spironolactone, Triamteren, amiloridom), potassium supplements, salt substitutes and food supplements, containing potassium, may develop hyperkalemia (especially in patients with impaired renal function), tk. ACE inhibitors reduce aldosterone, which leads to a delay of potassium in the body amid restrictions potassium excretion or additional intake of.

With simultaneous use of ACE inhibitors and NSAIDs increases the risk of renal dysfunction; rarely observed hyperkalemia.

Together with the application “loop” diuretics or thiazide diuretics can be marked hypotension, especially after the first dose of the diuretic, apparently, by hypovolemia, which leads to a transient enhancement of the antihypertensive action of captopril. There is a risk of hypokalemia. Increased risk of renal dysfunction.

In an application with the means for anesthesia, severe hypotension.

While the use of azathioprine may develop anemia, due to inhibition of the activity of erythropoietin under the influence of ACE inhibitors and azathioprine. There are cases of leucopenia, that may be due to additive inhibition of bone marrow function.

In an application with allopurinol increases the risk of haematological disorders; described cases of severe hypersensitivity reactions, including Stevens-Johnson syndrome.

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

Acetylsalicylic acid in high doses can reduce the antihypertensive effect of captopril. Definitively not set, whether aspirin 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, inhibiting the synthesis of prostaglandins and COX, can cause vasoconstriction, which leads to reduced cardiac output and deterioration in heart failure patients, receiving ACE inhibitors.

There are reports of increasing the concentration of digoxin in the blood plasma, while the use of captopril with digoxin. The risk of drug interactions increased in patients with impaired renal function.

In an application with indomethacin, ibuprofen reduced antihypertensive effect of captopril, apparently, influenced by inhibiting prostaglandin synthesis NSAIDS (that, believed, play a role in the development of hypotensive effect of ACE inhibitors).

While the use of insulin, sulfonylurea hypoglycemic agents may develop hypoglycemia due to increase glucose tolerance.

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

While the use of interferon alfa-2a, Interferon beta described cases of severe granulocytopenia.

In the transition from receiving clonidine on captopril antihypertensive effect last develops gradually. In the case of sudden clonidine patients, receiving captopril, possible sharp rise in blood pressure.

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

While the use of minoxidil, sodium nitroprusside increased antihypertensive effect.

While the use of orlistat may decrease the effectiveness of captopril, which may lead to increased blood pressure, hypertensive crisis, described a brain hemorrhage.

With simultaneous use of ACE inhibitors with pergolide may increase the antihypertensive effect.

In an application with probenecid reduces the renal clearance of captopril.

While the use of procainamide may increase the risk of leucopenia.

While the use of trimethoprim is a risk of hyperkalemia, especially in patients with impaired renal function.

In an application with chlorpromazine there is a risk of orthostatic hypotension.

At simultaneous application with cyclosporine has been reported the development of acute renal failure, oligurii.

It is believed, that may decrease the effectiveness of antihypertensive drugs, while the application with erythropoietin.