In this article, you can read the instructions for use medicinal product Diroton. Reviews of site visitors - consumers of this medicine, as well as opinions of doctors of specialists on the use of Diroton in their practice are presented. A big request to actively add your reviews about the drug: did the medicine help or not help get rid of the disease, what complications were observed and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Diroton in the presence of existing structural analogues. Use for treatment arterial hypertension and lowering blood pressure in adults, children, as well as during pregnancy and lactation.

Diroton- ACE inhibitor, reduces the formation of angiotensin 2 from angiotensin 1. A decrease in the content of angiotensin 2 leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces peripheral vascular resistance, blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and an increase in myocardial tolerance to stress in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on the tissue renin-angiotensin systems. With prolonged use, hypertrophy of the myocardium and walls of resistive arteries decreases. Improves blood supply to ischemic myocardium.

ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow down the progression of left ventricular dysfunction in patients with myocardial infarction without clinical manifestations heart failure.

The onset of action of the drug is after 1 hour, reaches a maximum after 6-7 hours and lasts for 24 hours. The duration of the effect also depends on the size of the dose taken. With arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months. With a sharp withdrawal of the drug, no pronounced increase in blood pressure was observed.

Diroton reduces albuminuria. In patients with hyperglycemia, it contributes to the normalization of the function of the damaged glomerular endothelium. Does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.

Hydrochlorothiazide

Thiazide diuretic, the diuretic effect of which is associated with a violation of the reabsorption of sodium, chlorine, potassium, magnesium, water ions in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties; hypotensive effect develops due to the expansion of arterioles. Virtually no effect on normal level HELL.

The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours. The antihypertensive effect occurs after 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

Lisinopril and hydrochlorothiazide, if used simultaneously, have an additive antihypertensive effect.

Compound

Lisinopril dihydrate + excipients.

Lisinopril dihydrate + Hydrochlorothiazide + excipients (KO-Diroton).

Pharmacokinetics

Lisinopril binds poorly to plasma proteins. Permeability through the blood-brain barrier (BBB) ​​and the placental barrier is low. Lisinopril is not metabolized. Excreted exclusively by the kidneys unchanged.

Indications

• essential and renovascular hypertension (as monotherapy or in combination with other antihypertensive drugs);
• chronic heart failure (as part of combination therapy);
• acute myocardial infarction (in the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevent left ventricular dysfunction and heart failure);
• diabetic nephropathy (to reduce albuminuria in patients with insulin-dependent diabetes mellitus with normal blood pressure and in patients with non-insulin-dependent diabetes mellitus with arterial hypertension).

Release form

Tablets 2.5 mg, 5 mg, 10 mg and 20 mg.

Tablets 10 mg and 20 mg (KO-Diroton).

Instructions for use and dosage

The drug is taken orally 1 time per day, for all indications, regardless of food intake, preferably at the same time of day.

In essential hypertension, patients who are not receiving other antihypertensive agents are prescribed 10 mg 1 time per day. The usual daily maintenance dose is 20 mg. The maximum daily dose is 40 mg.

The full effect usually develops after 2-4 weeks from the start of treatment, which should be taken into account when increasing the dose. With insufficient clinical effect, it is possible to combine the drug with other antihypertensive drugs.

If the patient received prior treatment with diuretics, then their intake must be stopped 2-3 days before the start of Diroton's use. If it is impossible to cancel diuretics, then the initial dose of Diroton should not exceed 5 mg per day. In this case, after taking the first dose, medical supervision is recommended for several hours (the maximum effect is reached after about 6 hours), because. a pronounced decrease in blood pressure may develop.

In case of renovascular hypertension or other conditions with increased RAAS activity, it is also advisable to prescribe a lower initial dose - 2.5-5 mg per day under enhanced medical supervision (control of blood pressure, kidney function, serum potassium concentration). The maintenance dose should be determined depending on the dynamics of blood pressure.

In chronic heart failure, the initial dose is 2.5 mg 1 time per day, which can be gradually increased after 3-5 days to the usual maintenance daily dose of 5-20 mg. The dose should not exceed the maximum daily dose 20 mg. At simultaneous application with diuretics in advance, if possible, the dose of the diuretic should be reduced. Before starting treatment with Diroton and later, during treatment, blood pressure, kidney function, potassium and sodium levels in the blood should be regularly monitored to avoid the development of arterial hypotension and associated renal dysfunction.

In acute myocardial infarction (as part of combination therapy) on the first day, 5 mg is prescribed, on the second day - again 5 mg, on the third day - 10 mg, maintenance dose - 10 mg 1 time per day. In patients with acute infarction myocardial infarction, the drug should be used for at least 6 weeks. With low systolic blood pressure (less than 120 mm Hg. Art.), Treatment begins with a low dose (2.5 mg per day). In the case of the development of arterial hypotension, when systolic blood pressure is less than 100 mm Hg. Art., the maintenance dose is reduced to 5 mg per day, if necessary, you can temporarily appoint 2.5 mg per day. In case of a prolonged pronounced decrease in blood pressure (systolic blood pressure below 90 mm Hg for more than 1 hour), treatment with the drug should be discontinued.

In diabetic nephropathy in patients with insulin-dependent diabetes mellitus, Diroton is used at a dose of 10 mg 1 time per day. If necessary, the dose can be increased to 20 mg 1 time per day in order to achieve diastolic blood pressure values ​​below 75 mm Hg. Art. in a sitting position. For patients with non-insulin-dependent diabetes mellitus, the drug is prescribed at the same dose, in order to achieve diastolic blood pressure values ​​below 90 mm Hg. in a sitting position.

Side effect

• pronounced decrease in blood pressure;
• chest pain;
• orthostatic hypotension;
• tachycardia;
• bradycardia;
• the appearance of symptoms of heart failure;
• violation of AV conduction;
• myocardial infarction;
• nausea, vomiting;
• stomach ache;
• dry mouth;
• diarrhea;
• dyspepsia;
• anorexia;
• taste disorder;
• hives;
• increased sweating;
• photosensitivity;
• pruritus;
• hair loss;
• mood lability;
• impaired concentration;
• paresthesia;
• increased fatigue;
• drowsiness;
• convulsive twitching of the muscles of the limbs and lips;
• asthenic syndrome;
• confusion;
• dry cough;
• bronchospasm;
• leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decreased hemoglobin concentration, hematocrit, erythrocytopenia), agranulocytosis;
• angioedema of the face, limbs, lips, tongue, epiglottis and / or larynx;
• vasculitis;
• increase in ESR;
• impaired renal function;
• acute renal failure;
• decrease in potency;
• arthritis;
• myalgia;
• fever;
• exacerbation of gout.

Contraindications

• idiopathic angioedema in history (including the use of ACE inhibitors);
• hereditary angioedema;
• age up to 18 years (efficacy and safety have not been established);
• hypersensitivity to lisinopril or other ACE inhibitors.

Use during pregnancy and lactation

The use of Diroton during pregnancy is contraindicated. Lisinopril crosses the placental barrier. When pregnancy is established, the drug should be discontinued as soon as possible. Taking ACE inhibitors in the 2nd and 3rd trimesters of pregnancy has an adverse effect on the fetus (a pronounced decrease in blood pressure, renal failure, hyperkalemia, skull hypoplasia, intrauterine death are possible). There are no data on the negative effects of the drug on the fetus in the case of use in the 1st trimester. For newborns and infants who have been exposed to ACE inhibitors in utero, it is recommended to establish careful monitoring for the timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia.

There are no data on the penetration of lisinopril into breast milk. If necessary, the appointment of the drug during lactation breast-feeding should be stopped.

special instructions

Most often, a pronounced decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, a decrease in the salt content in food, dialysis, diarrhea, or vomiting. In chronic heart failure with simultaneous renal failure or without it, a pronounced decrease in blood pressure is possible. More often, a pronounced decrease in blood pressure is detected in patients with a severe stage of chronic heart failure, as a result of the use of high doses of diuretics, hyponatremia, or impaired renal function. In such patients, treatment with Diroton should be started under the strict supervision of a physician (with caution, select the dose of the drug and diuretics).

Similar rules should be followed when prescribing Diroton to patients with coronary artery disease, cerebrovascular insufficiency, in whom a sharp decline AD can lead to myocardial infarction or stroke.

A transient hypotensive reaction is not a contraindication for taking the next dose of the drug.

Before starting treatment with Diroton, if possible, it is necessary to normalize the concentration of sodium and / or replenish the lost volume of fluid, carefully monitor the effect of the initial dose of Diroton on the patient's blood pressure.

Treatment of symptomatic hypotension consists of providing bed rest and, if necessary, IV fluids (saline infusion). transient arterial hypotension is not a contraindication for treatment with Diroton, however, it may be necessary to temporarily cancel it, or reduce the dose.

Treatment with Diroton is contraindicated in case of cardiogenic shock and in acute myocardial infarction, if the appointment of a vasodilator can significantly worsen hemodynamic parameters, for example, when systolic blood pressure does not exceed 100 mm Hg. Art.

In patients with acute myocardial infarction, a decrease in kidney function (plasma creatinine concentration of more than 177 μmol / l and / or proteinuria of more than 500 mg / 24 hours) is a contraindication for the use of Diroton. In the event of the development of renal failure during treatment with lisinopril (plasma creatinine concentration of more than 265 µmol / l or twice the baseline), the doctor should decide whether to stop treatment.

With bilateral stenosis of the renal arteries and stenosis of the renal artery of a single kidney, as well as with hyponatremia and / or a decrease in BCC or circulatory failure, arterial hypotension caused by taking the drug Diroton can lead to a decrease in kidney function with the subsequent development of reversible (after discontinuation of the drug) acute renal failure . A slight temporary increase in the concentration of urea in the blood and creatinine can be observed in cases of impaired renal function, especially against the background of concomitant treatment with diuretics. In cases of a significant decrease in kidney function (CC less than 30 ml / min), caution and monitoring of renal function is required.

Angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including the drug Diroton, which may occur during any period of treatment. In this case, treatment with Diroton should be stopped as soon as possible and the patient should be observed until the symptoms completely regress. In cases where swelling of only the face and lips has occurred, the condition most often resolves without treatment, however, it is possible to prescribe antihistamines. Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis or larynx are involved, airway obstruction may occur, so appropriate therapy (0.3-0.5 ml of epinephrine (adrenaline) 1: 1000 subcutaneously, administration of glucocorticosteroids, antihistamines) and / or measures to ensure airway patency should be immediately carried out. Patients with a history of angioedema unrelated to previous treatment with ACE inhibitors may be at an increased risk of developing it during treatment with an ACE inhibitor.

An anaphylactic reaction was also noted in patients on hemodialysis using high-flow dialysis membranes (AN69), who simultaneously take Diroton. In such cases, consideration should be given to using a different type of dialysis membrane or other antihypertensive agent.

In some cases of desensitization against arthropod allergens, treatment with ACE inhibitors was accompanied by hypersensitivity reactions. This can be avoided if you first temporarily interrupt the use of ACE inhibitors.

In patients undergoing major surgery or during general anesthesia ACE inhibitors (in particular, lisinopril) can block the formation of angiotensin 2. The decrease in blood pressure associated with this mechanism of action is corrected by an increase in BCC. Before surgery (including dentistry), it is necessary to warn the anesthesiologist about the use of Diroton.

The use of the recommended doses of the drug by elderly patients may be accompanied by an increase in the concentration of lisinopril in the blood, so the selection of the dose requires special attention and is carried out depending on the kidney function and the patient's blood pressure. However, in elderly and young patients, the antihypertensive effect of Diroton is equally pronounced.

When using ACE inhibitors, a cough was noted (dry, prolonged, which disappears after stopping treatment with ACE inhibitors). At differential diagnosis cough, it is necessary to take into account the cough caused by the use of ACE inhibitors.

In some cases, hyperkalemia was noted. Risk factors for developing hyperkalemia include kidney failure, diabetes, taking potassium supplements or drugs that cause an increase in the content of potassium in the blood (for example, heparin), especially in patients with impaired renal function.

During the period of drug treatment, regular monitoring of potassium, glucose, urea, and lipid ions in the blood plasma is necessary.

Caution should be exercised when exercising in hot weather (risk of dehydration and an excessive decrease in blood pressure due to a decrease in BCC).

Since the potential risk of agranulocytosis cannot be excluded, periodic monitoring of the blood picture is required.

Influence on the ability to drive vehicles and control mechanisms

When adverse reactions from the side of the central nervous system management is not recommended vehicles, as well as the performance of work associated with increased risk.

drug interaction

With simultaneous use with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, the risk of developing hyperkalemia increases, especially in patients with impaired renal function. Therefore, a joint appointment is possible only on the basis of an individual decision of the doctor with regular monitoring of the potassium content in the blood serum and kidney function.

With simultaneous use with beta-blockers, blockers of slow calcium channels, diuretics and other antihypertensive drugs, there is an increase in the hypotensive effect of the drug.

With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex is described, including facial flushing, nausea, vomiting, and arterial hypotension.

With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol (alcohol), the hypotensive effect of the drug is enhanced.

With simultaneous use with non-steroidal anti-inflammatory drugs (including selective COX-2 inhibitors), estrogens, and adrenomimetics, the antihypertensive effect of lisinopril decreases.

With simultaneous use with lithium preparations, the excretion of lithium from the body slows down (increased cardiotoxic and neurotoxic effects of lithium).

With simultaneous use with antacids and cholestyramine, absorption in the gastrointestinal tract decreases.

The drug enhances the neurotoxicity of salicylates, weakens the effect of oral hypoglycemic agents, norepinephrine, epinephrine and anti-gout drugs, enhances the effects (including side effects) of cardiac glycosides, the effect of peripheral muscle relaxants, and reduces the excretion of quinidine.

Reduces the effect of oral contraceptives.

At simultaneous reception methyldopa increases the risk of hemolysis.

Diroton's analogues

Structural analogues for the active substance:

• Dapril;
• Diropress;
• Irumed;
• Lizacard;
• Lysigamma;
• Lisinopril;
• Lisinopril dihydrate;
• Lisinoton;
• Lysonorm;
• Lizoril;
• Listril;
• Liten;
• Prinivil;
• Rileys-Sanovel;
• Sinopril.

In the absence of analogues of the drug for the active substance, you can follow the links below to the diseases that the corresponding drug helps with and see the available analogues for the therapeutic effect.

Co-Diroton: instructions for use and reviews

Latin name: Co-Diroton

ATX code: C09BA03

Active substance: Lisinopril + Hydrochlorothiazide (Lisinopril + Hydrochlorothiazide)

Manufacturer: Gedeon Richter (Hungary), Grodzisk Pharmaceutical Works Polfa Co. (Poland), Gedeon Richter Poland, Co. Ltd. (Poland)

Description and photo update: 27.07.2018

Co-Diroton is a combined drug with a diuretic, hypotensive effect, used in the treatment of arterial hypertension.

Release form and composition

Dosage form of release of Co-Diroton - tablets: round flat-cylindrical shape, with a chamfer; 10 mg + 12.5 mg - light blue, a few blotches of a darker color are possible, engraved on one side "C43"; 20 mg + 12.5 mg - light green, a few blotches of a darker color are possible, engraved on one side with "C44" (in a cardboard pack 1 or 3 blisters of 10 pieces each).

Active ingredients in 1 tablet:

• lisinopril - 10 or 20 mg (lisinopril dihydrate - 10.89 or 21.77 mg);
• hydrochlorothiazide - 12.5 mg.

Additional components (10 mg + 12.5 mg / 20 mg + 12.5 mg): magnesium stearate - 5/5 mg; mannitol - 50/50 mg; aluminum varnish based on indigotine dye (E 132) - 0.2 / 0.2 mg; dye iron oxide yellow (E 172) - 0 / 0.1 mg; partially pregelatinized starch - 2.25 / 2.25 mg; calcium hydrogen phosphate dihydrate - 136.8 / 136.7 mg; pregelatinized starch - 2.25 / 2.25 mg; corn starch - 31/31 mg.

Pharmacological properties

Pharmacodynamics

Co-Diroton is one of the combined drugs that have a diuretic and antihypertensive effect.

Lisinopril

It is an ACE inhibitor (angiotensin-converting enzyme), its action is aimed at reducing the formation of angiotensin II from angiotensin I, which, in turn, reduces the release of aldosterone.

It helps to reduce the degradation of bradykinin and increase the synthesis of prostaglandins. Reduces OPSS (total peripheral vascular resistance), blood pressure (blood pressure), pressure in the pulmonary capillaries, preload. Against the background of chronic heart failure, taking Co-Diroton leads to an increase in the minute volume of blood and an increase in exercise tolerance.

Lisinopril improves blood supply to ischemic myocardium. The expansion of the arteries occurs to a greater extent than the veins. Some effects can be explained by effects on tissue renin-angiotensin systems. Conducting a long course can reduce the severity of myocardial hypertrophy and arterial walls of the resistive type.

ACE inhibitors help prolong life expectancy in patients with chronic heart failure, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction, not accompanied by clinical manifestations of heart failure.

The development of the antihypertensive effect of Co-Diroton begins after about 6 hours, lasts 24 hours. Duration therapeutic action also determined by the dose. The onset of action of lisinopril is after 1 hour, the maximum effect is observed after 6-7 hours. The effect of the substance in arterial hypertension is observed in the first days after the start of administration, the development of a stable effect - after 1-2 months.

A pronounced increase in blood pressure with a sharp abolition of Co-Diroton is not observed.

In addition to lowering blood pressure, lisinopril helps to reduce albuminuria. In patients with hyperglycemia, it leads to the normalization of the function of the damaged glomerular endothelium.

Lisinopril has no effect on blood glucose concentrations in patients with diabetes mellitus. An increase in cases of hypoglycemia is not observed.

Hydrochlorothiazide

It is a thiazide diuretic. Its action is associated with a violation of the reabsorption of potassium, chlorine, sodium, magnesium, water ions in the distal nephron; delays the excretion of uric acid, calcium ions. The antihypertensive effect is due to the expansion of arterioles. It practically does not affect the normal level of blood pressure.

The development of the diuretic effect is observed after 1-2 hours, the maximum level is reached after 4 hours and persists for 6-12 hours. The antihypertensive effect occurs after 3-4 days; some patients require 3-4 weeks to achieve the optimal therapeutic effect.

Pharmacokinetics

Lisinopril

After oral administration, Cmax (maximum concentration) of lisinopril in serum is reached after 7 hours. The substance binds poorly to plasma proteins.

The average absorption rate is approximately 25%, with significant inter-individual variability (6-60%). Food does not affect the absorption of the substance.

Lisinopril is not metabolized and is excreted by the kidneys unchanged. After repeated administration of the drug, the effective T 1/2 (half-life) is 12 hours. In patients with impaired renal function, there is a slowdown in the excretion of the substance, but clinical significance it only has in cases where the speed glomerular filtration < 30 мл/мин.

In elderly patients, compared with younger patients, the level of C max and AUC (area under the concentration-time curve) is on average twice as high. Lisinopril is excreted from the body by hemodialysis.

Through the blood-brain barrier penetrates to a small extent.

Hydrochlorothiazide

The substance is not metabolized and is rapidly excreted by the kidneys. T 1/2 is in the range of 5.6–14.8 hours. At least 61% of the dose is excreted unchanged within 24 hours.

Through the blood-brain barrier hydrochlorothiazide does not penetrate, but penetrates through the placental.

Indications for use

Co-Diroton is prescribed for arterial hypertension in patients who are indicated for combination therapy.

Contraindications

Absolute:

• angioedema, including a history of Quincke's edema associated with the use of ACE inhibitors;
• anuria;
• < 30 мл/мин);
• hypercalcemia;
• hemodialysis, during which high-flow membranes are used;
• porphyria;
• hyponatremia;
• hepatic coma;
• precoma;
• severe diabetes mellitus;
• age up to 18 years;
• individual intolerance to any component of the drug, as well as other ACE inhibitors.

Relative (Co-Diroton is prescribed under medical supervision):

• arterial hypotension;
• liver failure;
• primary hyperaldosteronism;
• renal failure (in patients with creatinine clearance> 30 ml / min);
• aortic stenosis/hypertrophic cardiomyopathy;
• condition after kidney transplantation;
• stenosis of the artery of a single kidney with progressive azotemia;
• bilateral stenosis of the renal arteries;
• bone marrow hypoplasia;
• hyponatremia (due to an increased risk of arterial hypotension in patients on a low-salt or salt-free diet);
• ischemic disease hearts;
• hypovolemic conditions, including vomiting and diarrhea;
• hyperkalemia;
• connective tissue diseases, including systemic lupus erythematosus, scleroderma;
• hyperuricemia;
• diabetes;
• oppression of bone marrow hematopoiesis;
• gout;
• cerebrovascular diseases, including cerebrovascular insufficiency;
• chronic heart failure in severe course;
• elderly age.

Instructions for use of Co-Diroton: method and dosage

Co-Diroton is taken orally.

Usually prescribed 1 time per day, 1 tablet. If within 2-4 weeks due therapeutic effect is not achieved, a single dose can be increased by 2 times.

In patients with a creatinine clearance of 30-80 ml / min, Co-Diroton can only be used after individual selection of the dose of individual active ingredients.

In uncomplicated renal failure, the recommended starting dose of lisinopril is 5–10 mg.

After taking the initial dose of the drug, the development of symptomatic arterial hypotension may occur. More often such cases occur in patients with loss of fluid and electrolytes associated with previous treatment with diuretics. In this regard, 2-3 days before the start of the use of Co-Diroton, diuretics should be stopped.

Side effects

Most often, during the period of therapy, the development of dizziness and headache is observed.

Possible violations:

• digestive system: taste change, vomiting, nausea, abdominal pain, xerostomia, diarrhea, anorexia, dyspepsia, pancreatitis, cholestatic / hepatocellular hepatitis, jaundice;
• cardiovascular system: marked decrease in blood pressure, chest pain; rarely - myocardial infarction, impaired AV conduction, orthostatic hypotension, bradycardia, tachycardia, symptoms of heart failure;
• central nervous system: increased fatigue, mood lability, impaired concentration, paresthesia, drowsiness, convulsive twitching of the muscles of the lips and limbs; rarely - confusion, asthenic syndrome;
• skin: urticaria, photosensitivity, increased sweating, pruritus, alopecia;
• hematopoietic system: agranulocytosis, leukopenia, neutropenia, thrombocytopenia, anemia (decreased hematocrit, hemoglobin, erythrocytopenia);
• respiratory system: bronchospasm, dry cough, dyspnea, apnea;
• genitourinary system: reduced potency, uremia, oliguria and / or anuria, acute renal failure, impaired renal function;
• laboratory indicators: hypo- or hyperkalemia, hypomagnesemia, hyponatremia, hypercalcemia, hypochloremia, hyperuricemia, hyperglycemia, increased levels of urea and creatinine in blood plasma, hypercholesterolemia, hyperbilirubinemia, hypertriglyceridemia, decreased glucose tolerance, increased activity of hepatic transaminases, especially when indicated in a history of kidney disease, renovascular hypertension and diabetes mellitus;
• allergic reactions: angioedema of the tongue, face, lips, extremities, larynx and / or epiglottis, vasculitis, skin rashes, fever, itching, positive reactions to antinuclear antibodies, eosinophilia, increased ESR;
• others: exacerbation of gout, myalgia, arthralgia, arthritis, impaired fetal development, fever.

Overdose

The main symptoms: drowsiness, xerostomia, a pronounced decrease in blood pressure, urinary retention, irritability, anxiety, constipation.

In case of overdose, symptomatic treatment is indicated, intravenous administration fluids, blood pressure control. It also requires correction of violations of the water-salt balance and dehydration under the control of urea, electrolytes and creatinine in the blood serum and diuresis.

special instructions

Most often, a pronounced decrease in blood pressure is observed with a decrease in the volume of fluid caused by the use of diuretics, a decrease in the amount of salt in food, dialysis, and diarrhea or vomiting.

In patients with chronic heart failure occurring with / without renal failure, a pronounced decrease in blood pressure is possible. More often it is detected in patients with a severe class of chronic heart failure as a result of the use of diuretics in large doses ah, hyponatremia or impaired renal function. Treatment in such patients should begin under strict medical supervision. Similar recommendations should be followed in cases of prescribing Co-Diroton to patients with coronary heart disease, cerebrovascular insufficiency, since in them a sharp decrease in blood pressure can cause myocardial infarction or stroke.

Transient arterial hypotension is not a contraindication for further therapy.

Before taking Co-Diroton, if possible, it is necessary to normalize the concentration of sodium and / or replenish the lost volume of fluid. Careful monitoring of the effect of the initial dose of the drug on the patient's condition is shown.

In chronic heart failure, a pronounced decrease in blood pressure after the start of therapy with ACE inhibitors can lead to a further deterioration in renal function. There are reports of cases of acute renal failure.

During the use of ACE inhibitors in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, an increase in urea and creatinine in the blood serum, as a rule, is reversible. More often this disorder occurs in patients with renal insufficiency.

Angioedema of the tongue, face, lips, extremities, larynx and / or epiglottis is rare when using Co-Diroton, but it can develop at any period of therapy. In such cases, the drug should be discontinued as soon as possible and close monitoring of the patient's condition should be established.

If the swelling extends only to the face and lips, the condition in most cases goes away without additional treatment however, antihistamines may be prescribed. With swelling of the larynx, a fatal outcome is possible. When the tongue, larynx, or epiglottis is involved, airway obstruction may occur, requiring immediate appropriate therapy (epinephrine solution 1:1000 subcutaneously in a volume of 0.3-0.5 ml) and / or measures to ensure airway patency.

With a burdened history of angioedema, not associated with previous treatment with ACE inhibitors, the risk of its development while taking Co-Diroton is assessed as increased.

In the differential diagnosis of dry, prolonged cough, the likelihood of a connection with lisinopril should be considered.

Lisinopril during major surgery/general anesthesia may block the formation of angiotensin II. A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, is eliminated by an increase in circulating blood volume.

When carrying out hemodialysis using dialysis membranes with high permeability (AN69), an anaphylactic reaction may develop. In such cases, consideration should be given to using a different antihypertensive agent or a different type of dialysis membrane.

Before surgery (including dentistry), you need to warn the anesthetist about taking Co-Diroton.

In some cases, the development of hyperkalemia was noted. Major risk factors include diabetes mellitus, kidney failure, potassium supplements or medicines, causing an increase in the concentration of potassium in the blood (in particular, heparin), especially with impaired renal function.

If there is a risk of symptomatic hypotension (compliance with a low-salt / salt-free diet) with / without hyponatremia, as well as in patients who received diuretics in high doses, the above conditions (loss of fluid and salts) should be compensated before starting treatment.

Thiazide diuretics can affect glucose tolerance, and therefore the doses of hypoglycemic agents for oral administration should be adjusted. When using thiazide diuretics, it is possible to reduce the excretion of calcium by the kidneys, causing hypercalcemia. Severe hypercalcemia may indicate latent hyperparathyroidism. Prior to the test to assess the function of the parathyroid glands, the use of Co-Diroton is recommended to be discontinued.

Due to the risk of dehydration and an excessive decrease in blood pressure associated with a decrease in circulating blood volume, in hot weather, as well as when exercising, patients should be careful.

During the period of therapy, regular monitoring of urea, lipids, glucose, and potassium in the blood plasma is required.

It is not recommended to consume alcoholic beverages during the treatment period, as this may lead to an increase in the hypotensive effect of Co-Diroton.

Influence on the ability to drive vehicles and complex mechanisms

Due to the possibility of developing dizziness, it is recommended to refuse to drive vehicles, especially at the beginning of the course.

Use during pregnancy and lactation

According to the instructions, Co-Diroton is not prescribed during pregnancy / lactation.

When pregnancy is established, the drug should be discontinued as soon as possible. In the II-III trimesters, taking lisinopril adversely affects the fetus (possible hypoplasia of the bones of the skull, renal failure, a pronounced decrease in blood pressure, hyperkalemia, intrauterine death). Information about the negative impact of Co-Diroton on the fetus in the case of its use in the first trimester is not presented. The condition of newborns / infants who have been exposed to intrauterine exposure to lisinopril should be evaluated by a doctor in order to timely detect violations (in the form of hyperkalemia, oliguria, a pronounced decrease in blood pressure).

Application in childhood

Co-Diroton is not prescribed to patients under 18 years of age, since its efficacy and safety in this category of patients have not been established.

For impaired renal function

• severe renal failure (in patients with creatinine clearance< 30 мл/мин), состояния после трансплантации почек: терапия противопоказана;
• renal failure (in patients with creatinine clearance> 30 ml / min): Co-Diroton is prescribed under medical supervision.

For impaired liver function

In hepatic insufficiency, therapy should be carried out with caution.

Use in the elderly

Co-Diroton can be used under medical supervision.

drug interaction

Interactions that may occur with the combined use of Co-Diroton with other drugs / substances:

• vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol: increased hypotensive effect;
• salicylates: enhancing their neurotoxicity;
• quinidine: decrease in its excretion;
• peripheral muscle relaxants: strengthening their action;
• methyldopa: increased risk of hemolysis;
• potassium-sparing diuretics, potassium-containing salt substitutes, potassium preparations: an increase in the likelihood of developing hyperkalemia, especially in the presence of impaired renal function (the combination can only be used as prescribed by a doctor under regular monitoring of kidney function and serum potassium levels in the blood);
• antacids and cholestyramine: a decrease in their absorption in the gastrointestinal tract;
• cardiac glycosides: enhancing their therapeutic / side effects;
• non-steroidal anti-inflammatory drugs (indomethacin and others), estrogens: a decrease in the antihypertensive effect of Co-Diroton;
• lithium preparations: slowing down the excretion of lithium from the body and increasing its neurotoxic / cardiotoxic effect;
• drugs with anti-gout action, norepinephrine, epinephrine, oral hypoglycemic drugs: weakening their action;
• oral contraceptives: decrease in their efficiency.

Analogues

The analogues of Co-Diroton are: Rileys-Sanovel plus, Lisinopril N STADA, Lisoretic, Lisinoton N, Skopril plus.

Terms and conditions of storage

Keep out of the reach of children, at a temperature not exceeding 30 °C.

Shelf life - 3 years.

Statistics indicate that the spike problem blood pressure familiar to 20-30 percent of the adult population. The consequences of a persistent increase in pressure (hypertension) are known to everyone: these are irreversible lesions internal organs(heart, blood vessels, brain, fundus, kidneys).

In the later stages, the situation worsens: weakness appears in the legs and arms, intelligence and memory decrease, coordination is impaired, vision deteriorates, and the risk of stroke increases.

Co-Diroton, a combined drug with a diuretic and antihypertensive effect, will help to avoid these complications. Before using the medicine, you should consult a doctor and read the instructions for use.

pharmachologic effect

Co-Diroton has a diuretic and hypotensive effect. The physiological action and biochemical effects of the drug are determined by its active components.

Hydrochlorothiazide is a diuretic from the thiazide group, which reduces the reabsorption of chlorine, potassium, sodium, water and magnesium in the distal nephrons.

It also delays the excretion of uric acid and calcium ions. The component promotes the expansion of arterioles, thereby lowering blood pressure. The diuretic effect is observed one or two hours after taking the pill, it becomes maximum after four hours, and lasts for 6-12 hours.

As for the antihypertensive effect, it becomes noticeable after 3-4 days. To see a persistent therapeutic effect, you need to take the medicine for at least 3-4 weeks.

Lisinopril is a typical ACE inhibitor that reduces the production of angiotensin II from angiotensin I and thereby lowers blood pressure.

The action of the component is aimed at increasing the synthesis of PG, reducing the degradation of bradykinin. It also reduces preload, blood pressure, peripheral vascular resistance and pressure in the pulmonary capillaries, increases tolerance to various loads in people with CHF, increases the minute volume of blood. Moreover, the veins expand more than the arteries. Long-term use of lisinopril improves blood supply to the ischemic myocardium, helps to reduce hypertrophy of the walls of arteries and myocardium.

Under the influence of lisinopril, albuminuria decreases, and in persons with hyperglycemia, the functions of the impaired glomerular endothelium are normalized.

Achievement of the maximum effect occurs after 6 hours. The effect of the drug can be observed for a day or more (depending on the dose taken). You can achieve a stable effect if you take lisinopril for one to two months.

The combination of hydrochlorothiazide and lisinopril provides an additive antihypertensive effect.

Indications for use on Co-Diroton

Assign as part of combination therapy to persons with hypertension.

Mode of application

Take the medicine inside one tablet per day. If within two to four weeks it is not possible to obtain the proper therapeutic effect, the specialist may decide to increase the dose to 2 tablets per day.

Renal failure: patients with Cl creatinine 30-80 ml / min can take Co-Diroton after selecting the dosage of the individual components. In uncomplicated renal failure, it is recommended to start treatment with 5-10 mg of lisinopril.

Prior diuretic therapy: after taking the initial dose of Co-Diroton, symptomatic arterial hypotension may develop. As a rule, this is characteristic of patients who have experienced electrolyte and fluid loss due to previous diuretic therapy. That is why two or three days before you start taking Co-Diroton, you need to stop taking diuretics.

Composition, release form

One tablet of the drug contains hydrochlorothiazide 12.5 mg and lisinopril 10 or 20 mg.

Auxiliary compounds used include: mannitol, magnesium stearate, corn starch, aluminum lacquer based on E 132, calcium hydrogen phosphate dihydrate, yellow iron oxide, pregelatinized and partially pregelatinized starch.

The form of tablets containing 20 mg of lisinopril is exactly the same. The only thing that differs is the color (here it is light green) and the inscription (“C44”).

Interaction with other drugs

The likelihood of developing hyperkalemia increases with the parallel use of potassium-sparing diuretics (Amiloride, Spironolactone, Triamteren), salt substitutes, potassium-containing agents. Especially people with functional disorders of the kidneys are susceptible to hyperkalemia.

The hypotensive effect is enhanced by the combination of Co-Diroton with vasodilators, barbiturates, ethanol-containing drugs, phenothiazines, tricyclic antidepressants.

The antihypertensive effect of lisinopril is reduced by the combined use of estrogen, NSAIDs (eg, indomethacin).

The process of lithium excretion slows down if you take Co-Diroton together with lithium preparations. The result is an increase in neurotoxic and cardiotoxic effects.

With antacids and cholestyramine, absorption from the gastrointestinal tract is reduced.

The use of Co-Diroton with oral contraceptives leads to a decrease in the effectiveness of the latter.

The drug can slow down the excretion of quinidine, increase the neurotoxicity of salicylates, enhance the effects (including unwanted and side effects) of peripheral muscle relaxants and cardiac glycosides, and also weaken the hypoglycemic effect of anti-gout agents, norepinephrine and epinephrine.

The hypotensive effect is enhanced by the use of ethanol during therapy.

With the combined use of methyldopa, the risk of hemolysis increases.

Side effects

The most common adverse reactions include dizziness and headaches. It is also possible to develop adverse reactions from the following body systems:

CCC	orthostatic hypotension, decrease in blood pressure clinically significant, impaired atrioventricular. conduction, tachycardia, myocardial infarction, chest pain, heart failure symptoms, bradycardia.
CNS	impaired attention and concentration, drowsiness, mood variability, confusion, twitching of the lips or extremities, asthenia, paresthesia.
Epidermis	increased sweating, itching, urticaria, photosensitivity, alopecia.
digestive tract	anorexia, dry mouth, abdominal pain, hepatitis, diarrhea, jaundice, vomiting, dyspepsia, pancreatitis, nausea.
Hematopoietic system	leukopenia, agranulocytosis, neutropenia, thrombocytopenia, anemia.
Respiratory system	apnea, dry cough, bronchospasm, dyspnea.
genitourinary system	uremia, reduced potency, acute renal failure, anuria, oliguria, impaired renal function.
The immune system	vasculitis, itching, positive reaction for antinuclear antibodies, eosinophilia, angioedema, skin rashes, fever, elevated ESR.
Metabolism	hypomagnesemia, hypochloremia, hyperglycemia, hypertriglyceridemia, hypercholesterolemia, increased activity of hepatic transaminases, hypo- or hyperkalemia, hyponatremia, hypercalcemia, hyperuricemia, hyperbilirubinemia, elevated levels of creatinine and urea.
Other	myalgia, exacerbation of gout, arthralgia, arthritis.

Overdose

In case of an overdose, a significant decrease in pressure, constipation, drowsiness, a feeling of increased irritability and anxiety, urinary retention, dry mouth are possible.

When such symptoms appear, symptomatic therapy is carried out, the introduction of intravenous fluids, pressure control, correction of dehydration and other disorders of the water-salt balance, as well as control of diuresis, concentration of electrolytes, creatinine and urea.

Contraindications

Co-Diroton is not prescribed for lactating and pregnant women, children and adolescents, and also in the presence of:

• hypersensitivity to hydrochlorothiazide, lisinopril, other ACE inhibitors, as well as additional compounds;
• angioedema (including the presence of a previous one);
• anuria;
• severe insufficiency of urinary function;
• precoma or hepatic coma;
• severe form of diabetes mellitus;
• porphyria;
• hyponatremia;
• hypercalcemia;
• the need for hemodialysis with high-flow membranes.

With caution, Co-Diroton is taken by the elderly and patients with:

• aortic stenosis, unilateral / bilateral stenosis of the renal arteries;
• arterial hypotension;
• hypertrophic cardiomyopathy;
• hypoplasia (underdevelopment) of the bone marrow;
• functional insufficiency of the kidneys with a decrease in the level of creatinine clearance to 30 ml / min;
• primary hyperaldosteronism;
• hypovolemic state (possibly as a result of vomiting or diarrhea);
• the need for recovery after a kidney transplant;
• connective tissue diseases (including scleroderma, SLE);
• gout;
• hyponatremia (including with a salt-free or low-salt diet);
• hyperkalemia;
• severe form of hepatic or chronic heart failure;
• diabetes mellitus;
• hyperuricemia;
• cerebrovascular diseases;
• suppressed bone marrow hematopoiesis.

During pregnancy

The appointment of Co-Diroton for pregnant women is prohibited, because. in the third and second trimesters of pregnancy, ACE inhibitors can cause a decrease in fetal blood pressure, hypoplasia of the skull bones, hyperkalemia, renal failure, and intrauterine death.

Infants and newborns exposed to intrauterine exposure to Co-Diroton and other ACE inhibitors should be under medical supervision.

This is necessary for the timely detection of hyperkalemia, oliguria, a strong decrease in blood pressure.

Terms and conditions of storage

In the place where Co-Diroton is stored, the air temperature should be up to +30 degrees. For safety reasons, the drug is stored in places inaccessible to animals and children.

The medicine can be used and stored for 3 years.

Price

Co-Diroton package price in Russia depends on the dosage. Tablets with 10 mg of lisinopril cost around 120-250 rubles, and tablets with 20 mg of lisinopril cost around 500-600 rubles.

Drug packaging in Ukraine costs around 60-140 hryvnia (depending on the number active substance and the number of tablets in the pack).

Analogues

Analogues of Co-Diroton include drugs Lizothiazide-Teva, Liprazid and Zoniksem.

Last update of the description by the manufacturer 07/15/2014

Filterable List

Active substance:

ATX

Pharmacological group

Nosological classification (ICD-10)

Compound

Description of the dosage form

Tablets 10 mg + 12.5 mg: round, flat-cylindrical, with a chamfer, light blue with a few patches of a darker color. On one side engraved "C43".

Tablets 20 mg + 12.5 mg: round, flat-cylindrical, with a chamfer, light green in color with a few patches of a darker color. On one side engraved "C44".

pharmachologic effect

pharmachologic effect diuretic, hypotensive.

Pharmacodynamics

Antihypertensive combination drug. It has antihypertensive and diuretic effects.

Lisinopril

ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of PG. Reduces peripheral vascular resistance, blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in minute blood volume and increased exercise tolerance in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on the tissue renin-angiotensin systems. With prolonged use, the severity of hypertrophy of the myocardium and the walls of the arteries of the resistive type decreases. Improves blood supply to ischemic myocardium. ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow down the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins after approximately 6 hours and persists for 24 hours. The duration of the effect also depends on the dose. The onset of action is after 1 hour. The maximum effect is determined after 6-7 hours. In arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months.

With a sharp withdrawal of the drug, there is no pronounced increase in blood pressure.

In addition to lowering blood pressure, lisinopril reduces albuminuria. In patients with hyperglycemia, it contributes to the normalization of the function of the damaged glomerular endothelium.

Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.

Hydrochlorothiazide

Thiazide diuretic, the diuretic effect of which is associated with a violation of the reabsorption of sodium, chlorine, potassium, magnesium, water ions in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties; hypotensive effect develops due to the expansion of arterioles. Virtually no effect on the normal level of blood pressure. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours and lasts for 6-12 hours. The antihypertensive effect occurs after 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

Lisinopril and hydrochlorothiazide, if used simultaneously, have an additive antihypertensive effect.

Pharmacokinetics

Lisinopril

After taking lisinopril inside Tmax - 7 hours Poorly associated with plasma proteins. The average degree of absorption of lisinopril is about 25%, with significant inter-individual variability (6-60%). Food does not affect the absorption of lisinopril. Lisinopril is not metabolized and is excreted unchanged exclusively by the kidneys. After repeated administration, the effective T 1/2 of lisinopril is 12 hours. Impaired renal function slows down the excretion of lisinopril, but this slowdown becomes clinically significant only when the glomerular filtration rate drops below 30 ml / min. In elderly patients, on average, the level of Cmax of the drug in the blood and AUC are 2 times higher compared to these indicators in younger patients. Lisinopril is excreted from the body by hemodialysis. To a small extent penetrates through the BBB.

Hydrochlorothiazide

It is not metabolized, but is rapidly excreted via the kidneys. T 1/2 of the drug ranges from 5.6 to 14.8 hours. At least 61% of the drug taken orally is excreted unchanged within 24 hours. Hydrochlorothiazide crosses the placental barrier, but does not penetrate the BBB.

Indications for Co-Diroton

Arterial hypertension (in patients who are indicated for combination therapy).

Contraindications

hypersensitivity to lisinopril, other ACE inhibitors or hydrochlorothiazide and excipients;

angioedema (including a history of Quincke's edema associated with the use of ACE inhibitors);

severe renal failure (Cl creatinine less than 30 ml / min);

hemodialysis using high-flow membranes;

hypercalcemia;

hyponatremia;

porphyria;

hepatic coma;

severe forms of diabetes;

age up to 18 years (efficacy and safety have not been established).

Carefully: aortic stenosis/hypertrophic cardiomyopathy; bilateral stenosis of the renal arteries; stenosis of the artery of a single kidney with progressive azotemia; condition after kidney transplantation; renal failure (Cl creatinine more than 30 ml / min); primary hyperaldosteronism; arterial hypotension; bone marrow hypoplasia; hyponatremia (increased risk of arterial hypotension in patients on a low-salt or salt-free diet); hypovolemic conditions (including diarrhea, vomiting); connective tissue diseases (including systemic lupus erythematosus, scleroderma); diabetes; gout; oppression of bone marrow hematopoiesis; hyperuricemia; hyperkalemia; cardiac ischemia; cerebrovascular diseases (including cerebrovascular insufficiency); severe chronic heart failure; liver failure; elderly age.

Use during pregnancy and lactation

The use of lisinopril during pregnancy is contraindicated. When pregnancy is established, the drug should be stopped as soon as possible. Taking ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (possible pronounced decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, intrauterine death). There are no data on the negative effects of the drug on the fetus if used during the first trimester. For newborns and infants who have been exposed to ACE inhibitors in utero, it is recommended to monitor for the timely detection of a pronounced decrease in blood pressure - oliguria, hyperkalemia.

During the period of drug treatment, it is necessary to stop breastfeeding.

Side effects

The most common side effects are dizziness, headache.

From the CCC: pronounced decrease in blood pressure, chest pain; rarely - orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, impaired AV conduction, myocardial infarction.

From the digestive tract: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, taste changes, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice.

From the side skin: urticaria, increased sweating, photosensitivity, pruritus, hair loss.

From the side of the central nervous system: mood lability, impaired concentration, paresthesia, fatigue, drowsiness, convulsive twitching of the muscles of the limbs and lips; rarely - asthenic syndrome, confusion.

From the respiratory system: dyspnea, dry cough, bronchospasm, apnea.

From the hematopoietic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decreased hemoglobin concentration, hematocrit, erythrocytopenia).

Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx (see "Special instructions"), skin rashes, itching, fever, vasculitis, positive reactions to antinuclear antibodies, increased ESR, eosinophilia.

From the side genitourinary system: uremia, oliguria/anuria, impaired renal function, acute renal failure, reduced potency.

Laboratory indicators: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, hypercalcemia, hyperuricemia, hyperglycemia, increased plasma urea and creatinine, hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, decreased glucose tolerance, increased liver transaminase activity, especially in the presence of a history of kidney disease , diabetes mellitus and renovascular hypertension.

Others: arthralgia, arthritis, myalgia, fever, impaired fetal development, exacerbation of gout.

Interaction

With simultaneous use with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium,- the risk of developing hyperkalemia increases, especially in patients with impaired renal function. Therefore, they can be jointly prescribed only on the basis of an individual decision of the doctor with regular monitoring of the level of potassium in the blood serum and kidney function.

With simultaneous use:

- with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol- strengthening of hypotensive action;

- NSAIDs (indomethacin and others), estrogen- decrease in the antihypertensive effect of lisinopril;

- lithium preparations- slowing down the excretion of lithium from the body (increased cardiotoxic and neurotoxic effects of lithium);

- antacids and cholestyramine- Decreased absorption in the gastrointestinal tract.

The drug enhances the neurotoxicity of salicylates, weakens the effect of hypoglycemic drugs for oral administration, norepinephrine, epinephrine and anti-gout drugs, enhances the effects (including side effects) of cardiac glycosides, the effect of peripheral muscle relaxants, reduces the excretion of quinidine.

Reduces the effect of oral contraceptives. Ethanol enhances the hypotensive effect of the drug. With the simultaneous administration of methyldopa, the risk of hemolysis increases.

Dosage and administration

inside. 1 tab. drug Co-Diroton containing lisinopril + hydrochlorothiazide 10 + 12.5 mg or 20 + 12.5 mg, 1 time per day. If the proper therapeutic effect is not obtained within 2-4 weeks, the dose of the drug can be increased to 2 tablets, applied 1 time per day.

Kidney failure: in patients with Cl creatinine from 30 and less than 80 ml / min, the drug can be used only after selecting the dose of the individual components of the drug. The recommended starting dose of lisinopril for uncomplicated renal failure is 5-10 mg.

Prior diuretic therapy: symptomatic arterial hypotension may occur after taking the initial dose of the drug. Such cases are more common in patients who have had loss of fluid and electrolytes due to previous treatment with diuretics. Therefore, it is necessary to stop taking diuretics 2-3 days before the start of treatment with the drug (see "Special Instructions").

Overdose

Symptoms: pronounced decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability.

Treatment: symptomatic therapy, intravenous fluid administration, blood pressure control; therapy aimed at correcting dehydration and disorders of the water-salt balance, controlling the level of urea, creatinine and electrolytes in the blood serum, as well as diuresis.

special instructions

Symptomatic arterial hypotension

Most often, a pronounced decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, a decrease in the amount of salt in food, dialysis, diarrhea or vomiting (see "Interaction" and " Side effects"). In patients with chronic heart failure with simultaneous renal failure or without it, a pronounced decrease in blood pressure is possible. It is more often detected in patients with a severe class of chronic heart failure as a result of the use of large doses of diuretics, hyponatremia, or impaired renal function. In such patients, treatment should begin under the strict supervision of a physician. Similar rules must be followed when prescribing to patients with IHD, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

Transient arterial hypotension is not a contraindication for further administration of the drug.

Before starting treatment, if possible, it is necessary to normalize the concentration of sodium and / or replenish the lost volume of fluid, carefully monitor the effect of the initial dose of the drug on the patient.

Impaired kidney function

In patients with chronic heart failure, a pronounced decrease in blood pressure after the start of treatment with ACE inhibitors can lead to a further deterioration in renal function. Cases of acute renal failure have been reported.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney treated with ACE inhibitors, there was an increase in the level of urea and creatinine in the blood serum, usually reversible after discontinuation of treatment. More common in patients with renal insufficiency.

Hypersensitivity/angioneurotic edema

Angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including lisinopril, and may occur at any time during treatment. In this case, treatment with lisinopril should be discontinued as soon as possible and the patient should be observed until complete regression of symptoms. In cases where swelling of only the face and lips has occurred, the condition most often resolves without treatment, but antihistamines may be prescribed. Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis, or larynx are involved, airway obstruction may occur, so appropriate therapy should be given immediately - 0.3-0.5 ml of epinephrine (adrenaline) 1:1000 s / c - and / or measures to ensure airway patency .

Patients with a history of angioedema unrelated to previous treatment with ACE inhibitors may be at an increased risk of developing it during treatment with an ACE inhibitor.

Cough

Cough has been reported with the use of an ACE inhibitor. Cough dry, prolonged, which disappears after discontinuation of treatment with an ACE inhibitor. In the differential diagnosis of cough, cough caused by the use of ACE inhibitors must also be taken into account.

Patients on hemodialysis

An anaphylactic reaction has also been reported in patients undergoing hemodialysis using high permeability dialysis membranes (AN69®) who are concomitantly taking ACE inhibitors. In such cases, consideration should be given to using a different type of dialysis membrane or other antihypertensive agent.

Surgery/general anesthesia

When using drugs that reduce blood pressure in patients with extensive surgery or during general anesthesia, lisinopril can block the formation of angiotensin II. A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by an increase in BCC. Before surgery (including dentistry), it is necessary to warn the anesthesiologist about the use of ACE inhibitors.

Serum potassium

In some cases, hyperkalemia was noted.

Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, taking potassium supplements or drugs that cause an increase in the concentration of potassium in the blood (eg heparin), especially in patients with impaired renal function.

In patients at risk of symptomatic hypotension (on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, the above conditions must be compensated before starting treatment (loss of fluid and salts).

Metabolic and endocrine effects

Thiazide diuretics can affect glucose tolerance, so it is necessary to adjust the dose of hypoglycemic agents for oral administration. Thiazide diuretics can reduce calcium excretion by the kidneys and cause hypercalcemia. Severe hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended to stop treatment with thiazide diuretics until a test to assess the function of the parathyroid glands.

During the period of treatment with the drug, regular monitoring of potassium, glucose, urea, and lipids in the blood plasma is necessary. During the treatment period, it is not recommended to drink alcoholic beverages, because. alcohol enhances the hypotensive effect of the drug.

Auxiliary compounds used: mannitol, pregelatinized, partially pregelatinized and corn starch, magnesium stearate, calcium hydrogen phosphate dihydrate, aluminum varnish based on indigotine dye (E 132), and iron oxide yellow (E 172).

Release form

Tablets Co-Diroton 10 mg + 12.5 mg have a round, flat-cylindrical shape and a chamfer, light blue in color, which may be with a few darker patches. A distinctive feature is the inscription "C43".

Tablets with a dosage of 20 mg + 12.5 mg also have a round, flat-cylindrical shape and a chamfer, but differ in color - in this case it is light green, engraved in the form of the inscription "C44".

pharmachologic effect

Co-Diroton tablets have a hypotensive and diuretic effect.

Pharmacodynamics and pharmacokinetics

biochemical effects and physiological action Co-Diroton is determined by its two active ingredients:

• Lisinopril known as an ACE inhibitor that reduces the production of angiotensin I V II , which leads to a direct decrease in excretion. Action lisinopril aimed at reducing degradation bradykinin and increased synthesis PG . In addition, it reduces OPSS , and in the pulmonary capillaries, preload, increasing the minute volume of blood and increasing tolerance to various types stress in patients with chronic heart failure. Dilation occurs more in the arteries than in the veins. Some of the effects are explained by the effect on renin-angiotensin system fabrics. Long-term use leads to a decrease in myocardial hypertrophy, arterial walls, and contributes to a better blood supply to the ischemic myocardium. It takes 6 hours to achieve the maximum effect, it can last 24 hours or more, depending on the dose. It takes 1-2 months to achieve a stable effect. therapy. Under influence active substance is also declining HELL and decreases albuminuria . For individuals with hyperglycemia there is a normalization of the functions of the disturbed glomerular endothelium.
• Hydrochlorothiazide is a thiazide diuretic associated with impaired reabsorption of chloride, sodium, potassium, magnesium and water ions in the distal nephrons. It is able to delay the excretion of calcium ions and uric acid . Hypotensive effect is based on the expansion of arterioles, without affecting the natural level HELL . The diuretic effect is observed after 1-2 hours and reaches its maximum after 4 hours, the therapeutic effect persists for 6-12 hours. The antihypertensive effect occurs after 3-4 days, 3-4 weeks are needed to achieve a stable therapeutic effect. therapy
• Combination lisinopril And hydrochlorothiazide produces an additive antihypertensive effect.

Pharmacokinetic data on lisinopril

As a result of oral administration lisinopril the maximum half-life is 7 hours. The substance binds weakly to plasma proteins. The substance is characterized average degree absorption is approximately 25%, significant interindividual variability is 6-60 percent. The diet has no effect on the absorption of lisinopril. It does not undergo transformation and is excreted by the kidneys; if they are disturbed, excretion slows down and becomes clinically significant. QC 30 ml/min. Cmax increases by 2 times in elderly patients. Lisinopril is able to penetrate the BBB in a small amount.

Pharmacokinetic data on hydrochlorothiazide

without being metabolized hydrochlorothiazide rapidly excreted by the kidneys. The substance is able to penetrate the placental, however, not through the blood-brain barrier. The half-life varies between 5.6-14.8 hours. Approximately 61% is excreted in a day.

Indications for use

As part of combination therapy for arterial hypertension .

Contraindications

• hypersensitivity to lisinopril , hydrochlorothiazide , other ACE inhibitors and auxiliary connections;
• (including the presence of an entry in the anamnesis);
• severe insufficiency of urinary function;
• high flow membranes;
• porphyria ;
• hypercalcemia ;
• hyponatremia ;
• precoma or hepatic coma ;
• severe form;
• pregnancy and lactation;
• not applicable in pediatrics (under 18 years of age).

Instructions for use with caution

• bilateral / unilateral renal arteries either;
• post-transplantation period after kidney transplantation;
• hypertrophic cardiomyopathy ;
• functional insufficiency of the kidneys with a reduced level creatinine clearance up to 30 ml/min;
• arterial hypotension ;
• primary hyperaldosteronism ;
• hypoplasia (underdevelopment) of the bone marrow;
• hyponatremia (including at low-salt or salt-free );
• hypovolemic state (possibly as a result of diarrhea or vomiting);
• connective tissue diseases (including systemic lupus erythematosus, scleroderma);
• diabetes ;
• hyperuricemia ;
• hyperkalemia ;
• suppressed bone marrow hematopoiesis;
• cerebrovascular diseases;
• severe form of chronic heart or liver failure;
• elderly patients.

Side effects

Most frequent adverse reactions- dizziness and headache. In addition, the following adverse reactions may occur from the systems of the human body:

• CCC: clinically significant decrease in blood pressure, chest pain, orthostatic hypotension , bradycardia , symptoms of heart failure, violation of atrioventr. conductivity is possible.
• Digestive system : nausea, anorexia , vomiting, dry mouth, diarrhea, dyspepsia, abdominal pain, hepatitis , jaundice.
• Epidermis: , increased sweating, photosensitivity , itching , alopecia .
• CNS: mood volatility, impaired concentration and attention, paresthesia , asthenia , drowsiness , twitching of limbs or lips, confusion.
• Respiratory system: bronchospasm , apnea , dyspnea , .
• Hematopoietic system: neutropenia , leukopenia , thrombocytopenia , anemia .
• The immune system: , vasculitis , skin rash, itching, positive reaction to antinuclear antibodies, eosinophilia .
• genitourinary system: anuria , uremia , oliguria , decreased potency, impaired renal function, the development of acute renal failure.
• Metabolism: hyper or hypokalemia , hypomagnesemia , hyponatremia , hypochloremia , hypercalcemia , hyperglycemia , hyperuricemia , hypertriglyceridemia , hyperbilirubinemia , hypercholesterolemia , elevated level urea , as well as increased activity of hepatic transaminases.
• Others: arthralgia , myalgia , exacerbation .

Instructions for use of Co-Diroton (Method and dosage)

Tablets are usually taken orally 1 piece once a day. If the desired therapeutic effect has not been achieved in 2-4 weeks, then the daily dose can be increased to 2 tablets.

Instructions for Co-Diroton in renal failure

An individual selection of doses of individual components is required. It is recommended to start therapy lisinopril with 5–10 mg.

Overdose

Predicted Symptoms

A significant decrease in blood pressure, urinary retention, constipation, dry mouth, drowsiness, a feeling of anxiety and increased irritability.

Method of treatment

Symptomatic therapy, intravenous fluid administration and correction dehydration and other violations water-salt balance , control of blood pressure, as well as concentration urea , creatinine , electrolytes , .

Interaction

• While taking the drug Co-Diroton together with potassium-sparing diuretics : , Triamterene , Amiloride , potassium-containing products, salt substitutes increases the likelihood hyperkalemia especially in patients with functional disorders kidneys.
• WITH vasodilators , phenothiazines , barbiturates , tricyclic antidepressants , ethanol-containing agents increase the hypotensive effect.
• WITH NSAIDs (for example,), the antihypertensive effect is reduced lisinopril .
• With drugs lithium slowing down the excretion process lithium , which enhances the cardiotoxic and neurotoxic effects.
• WITH Colestyramine And antacids reduced absorption from the gastrointestinal tract.
• Co-Diroton is able to increase neurotoxicity salicylates , weaken the hypoglycemic effect , Norepinephrine , and anti-gout agents, enhance effects (including side and undesirable) cardiac glycosides , peripheral muscle relaxants , reduce the rate of withdrawal Quinidine .
• The combination with oral contraceptives reduces their effectiveness.
• WITH ethanol Co-Diroton enhances the hypotensive effect.
• WITH methyldopa increased risk of hemolysis.

Terms of sale

This drug is sold by prescription.

Storage conditions

The temperature must not exceed +30 °C.

For safety reasons, keep out of the reach of children and animals.

Best before date

Can be stored and used for 3 years.

During pregnancy and lactation

Co-Diroton is contraindicated, since ACE inhibitors in the 2nd and 3rd trimester of pregnancy can cause a decrease in blood pressure in the fetus, kidney failure, hyperkalemia , hypoplasia of the bones of the skull, and even - intrauterine death .

Newborns and infants exposed in utero to drugs that are ACE inhibitors require medical monitoring in order to timely detect a pronounced decrease in blood pressure, as well as oliguria And hyperkalemia .

Analogues

Coincidence in the ATX code of the 4th level:

• Zoniksem ;
• Lysothiazide-Teva .