Diroton Plus caps 1.5mg + 5mg #28

Diroton Plus user manual

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Release form and composition

Dosage form - capsules with modified release: hard gelatin, size No. 1, light pink (dosage 1.5 mg + 5 mg), pink (dosage 1.5 mg + 10 mg) or red-brown (dosage 1.5 mg + 20 mg) (in a cardboard box 1, 2, 4 or 8 blisters of 14 capsules and instructions for use of Diroton Plus).
Composition of capsules containing active substances:
    dosage 1.5 mg + 5 mg: one white biconvex oval film-coated tablet engraved with "CP3" on one side and with a scored on the other, containing indapamide in an amount of 1.5 mg, and one white round biconvex tablet with engraving "CN3" on one side containing 5 mg lisinopril (as lisinopril dihydrate 5.444 mg);
    dosage 1.5 mg + 10 mg: one white biconvex oval film-coated tablet engraved with "CP3" on one side and with a scored on the other, containing indapamide in an amount of 1.5 mg, and one white round biconvex tablet with engraving "CN4" on one side, containing lisinopril 10 mg (as lisinopril dihydrate 10.888 mg);
    dosage 1.5 mg + 20 mg: one white biconvex oval film-coated tablet engraved with "CP3" on one side and with a scored on the other, containing indapamide in an amount of 1.5 mg, and two white round biconvex tablets with engraving "CN4" on one side containing 20 mg of lisinopril (as lisinopril dihydrate 21.776 mg).
Auxiliary components (1.5 mg + 5 mg / 1.5 mg + 10 mg / 1.5 mg + 20 mg, respectively):
    tablets: microcrystalline cellulose PH 102 - 9/9/9 mg; lactose monohydrate - 84/84/84 mg; talc - 2.5 / 2.5 / 5 mg; colloidal silicon dioxide - 0.75 / 0.75 / 0.75 mg; magnesium stearate - 2.42 / 2.42 / 4.09 mg; calcium hydrogen phosphate dihydrate - 58.566 / 53.122 / 106.244 mg; mannitol - 16.67 / 16.67 / 33.34 mg; hypromellose (type 2208) - 49.5 / 49.5 / 49.5 mg; corn starch - 12.15 / 12.15 / 24.3 mg; croscarmellose sodium - 3/3/6 mg;
    capsule (gelatin - 83.16 / 83.12 / 83.98%; crimson dye Ponso 4R - 0 / 0.383 2 / 0.215 6%; dye iron oxide red - 0.118 / 0 / 0.5%; titanium dioxide - 2.226 3 / 2 / 0.8%; water - 14.5 / 14.5 / 14.5%) - 76/76/76 mg;
    shell: Opadry II white (macrogol-3350 - 20.2 / 20.2 / 20.2%; titanium dioxide - 25/25/25%; polyvinyl alcohol - 40/40/40%; talc - 14.8 / 14 , 8 / 14.8%) - 4.5 / 4.5 / 4.5 mg.

Pharmacodynamics

Diroton Plus is a combination drug with fixed doses of indapamide and lisinopril.

Indapamide

Indapamide is a sulfonamide derivative containing an indole ring. In terms of pharmacological properties, the substance is close to thiazide-like diuretics, which inhibit the reabsorption of sodium ions in the cortical segment of Henle's loop. This is accompanied by an increase in the excretion of sodium, potassium and chloride ions, as well as, to a lesser extent, magnesium ions, due to which there is an increase in diuresis and an antihypertensive effect. When conducting clinical studies of phases II and III of monotherapy with indapamide in doses that do not lead to a pronounced diuretic effect, the substance caused an antihypertensive effect for 24 hours.
Due to the antihypertensive activity of indapamide, the elasticity index of large arteries improves and the total peripheral and arteriolar resistance decreases.
The use of indapamide helps to reduce left ventricular hypertrophy.
With therapy in certain doses, the optimal therapeutic effect of thiazide-like and thiazide diuretics can be achieved, however, if you continue to increase the dose, the frequency of side effects increases. Thus, if the effect is not observed when using Diroton Plus in the recommended therapeutic dose, the dose should not be increased.
When carrying out short-term, medium-term and long-term studies, in which patients with arterial hypertension took part, it was found that indapamide does not affect lipid (including the concentration of cholesterol, triglycerides, low and high density lipoproteins) and carbohydrate metabolism ( including against the background of diabetes mellitus).

Lisinopril

Lisinopril is one of the ACE inhibitors (angiotensin-converting enzyme). Its action is aimed at suppressing the conversion of angiotensin I to angiotensin II. With a decrease in the concentration of angiotensin II, there is a direct decrease in the secretion of aldosterone. Lisinopril suppresses the degradation of bradykinin and increases the biosynthesis of prostaglandins. The substance also reduces blood pressure, total peripheral vascular resistance, preload and pressure in the pulmonary capillaries.
In chronic heart failure, lisinopril helps to increase the minute blood volume and myocardial tolerance to stress. The expansion of the arteries occurs to a greater extent than the veins. Some of the effects of lisinopril can be explained by the effect on the tissue renin-angiotensin system. With prolonged use, there is a decrease in myocardial hypertrophy and the walls of resistive arteries.
Thanks to the use of lisinopril, the blood supply to the ischemic myocardium is improved.
ACE inhibitors in the setting of chronic heart failure increase life expectancy. Lisinopril with a burdened history of myocardial infarction without clinical manifestations of heart failure helps to slow the progression of left ventricular dysfunction.
After oral administration, lisinopril begins to act within one hour. The maximum effect develops in 6-7 hours, the duration of the therapeutic effect is 24 hours. The effect of therapy in patients with arterial hypertension is manifested during the first days after the start of treatment, a stable effect develops within 1–2 months of daily therapy. After the abrupt withdrawal of lisinopril, cases of a pronounced increase in blood pressure (blood pressure) were not recorded. In addition to blood pressure, Diroton Plus also lowers albuminuria. In patients with impaired function of the glomerular endothelium against the background of hyperglycemia, lisinopril helps to restore it.
In patients with diabetes mellitus, Diroton Plus has no effect on the concentration of glucose in the blood plasma; taking lisinopril is not associated with an increased risk of hypoglycemia.

Pharmacokinetics

Indapamide

The active ingredient is applied to a special matrix carrier, which provides a slow controlled release of indapamide in the gastrointestinal tract.
The released indapamide is completely and rapidly absorbed in the gastrointestinal tract. With simultaneous use with food, the absorption time of indapamide slightly increases, while the amount of absorption does not change.
The time to reach Cmax (maximum concentration of the substance) after a single dose is 12 hours. With repeated use of Diroton Plus, changes in plasma concentration in the blood between doses of indapamide are smoothed out.
The degree of absorption has individual variability.
About 79% of the dose binds to plasma proteins. The average T1 / 2 (half-life) is 18 hours (from 14 to 24 hours). Equilibrium concentrations after the start of therapy are reached within 7 days. Repeated use of Diroton Plus does not lead to cumulation.
The excretion of indapamide is carried out mainly in the form of an inactive metabolite by the kidneys and through the intestines (70 and 22%, respectively).

Lisinopril

After oral administration of lisinopril, approximately 25% of the dose is absorbed in the gastrointestinal tract. Food intake does not affect absorption. The average level of absorption is 30%, bioavailability is 29%.
Cmax in blood plasma after oral administration is achieved in 6-8 hours. The substance has a low degree of binding to plasma proteins. Lisinopril poorly penetrates the blood-brain barrier.
Lisinopril does not undergo biotransformation in the human body. T1 / 2 is 12 hours.
Indications for use
Diroton Plus is prescribed for the treatment of essential arterial hypertension in patients who are indicated for combination therapy.

Contraindications

Absolute:
    severe renal failure (with creatinine clearance <30 ml / min);
    severe liver dysfunction or hepatic encephalopathy;
    hypokalemia;
    combination therapy with drugs containing aliskiren in patients with impaired renal function (with a glomerular filtration rate <60 ml / min / 1.73 m2) or diabetes mellitus;
    burdened history of angioedema (including Quincke's edema) associated with the use of ACE inhibitors;
    idiopathic or hereditary angioedema;
    galactosemia, lactose intolerance, galactose and glucose malabsorption syndrome;
    pregnancy and lactation;
    age up to 18 years;
    individual intolerance to the components of Diroton Plus, as well as other ACE inhibitors and sulfonamide derivatives.
Relative (Diroton Plus capsules are used under close medical supervision):
    hepatic / renal failure;
    renal artery stenosis in the presence of a single kidney, bilateral renal artery stenosis;
    condition after kidney transplantation;
    severe autoimmune systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma);
    aortic stenosis;
    hypertrophic obstructive cardiomyopathy;
    cerebrovascular diseases (including cerebrovascular insufficiency);
    coronary insufficiency;
    coronary heart disease;
    myelosuppression;
    diabetes;
    azotemia;
    hyperkalemia;
    adherence to a diet with limited salt;
    primary aldosteronism;
    lengthening on the ECG (electrocardiogram) of the QT interval;
    conditions that are associated with a decrease in circulating blood volume (including vomiting and diarrhea);
    violations of water and electrolyte balance;
    hyperparathyroidism;
    high serum uric acid concentration in the blood;
    a weakened condition in patients or patients receiving combined treatment with other antiarrhythmic drugs;
    elderly age.

Diroton Plus, instructions for use: method and dosage

Diroton Plus capsules are taken orally, regardless of food intake, daily, preferably at the same time in the morning.
Fixed-dose combination drugs should generally not be used for initial therapy. Diroton Plus should be prescribed to patients who have achieved adequate control of arterial hypertension when using lisinopril and indapamide at the doses present in the combined preparation.
The recommended dose is 1 capsule per day (maximum).
If necessary, dose selection indapamide and lisinopril should be used separately.
In case of impaired renal function during the period of therapy, it is necessary to monitor their function, as well as the plasma content of sodium and potassium in the blood. If the renal function deteriorates, Diroton Plus is canceled and replaced with individually selected drugs.
In elderly patients, it is necessary to monitor the plasma concentration of creatinine in the blood and assess its compliance with age, sex and weight.

Side effects

The adverse events described below have been reported with lisinopril and indapamide as monotherapy and are classified according to the frequency of development:> 10% - very often; > 1% and <10% - often; > 0.1% and <1% - infrequently; > 0.01% and <0.1% - rarely; <0.01% - very rare; with an unspecified frequency - based on the available data, it is not possible to estimate the incidence of adverse reactions.
Adverse events associated with the use of indapamide
    nervous system: rarely - headache, asthenia, paresthesia, dizziness; with an unknown frequency - fainting;
    blood and lymphatic system: very rarely - leukopenia, thrombocytopenia, agranulocytosis, hemolytic and aplastic anemia;
    gastrointestinal tract: infrequently - vomiting; rarely - constipation, nausea, xerostomia; very rarely - pancreatitis;
    cardiovascular system: very rarely - severe arterial hypotension, arrhythmia; with an unknown frequency - pirouette-type ventricular tachycardia (is life-threatening);
    kidneys and urinary tract: very rarely - renal failure;
    skin and subcutaneous tissues: very often - hypersensitivity reactions (mainly dermatological, occur in patients with a predisposition to asthmatic and allergic reactions); often - maculopapular rash; infrequently - hemorrhagic vasculitis; very rarely - toxic epidermal necrolysis, urticaria and / or angioedema, Stevens-Johnson syndrome; with an unspecified frequency - deterioration in acute systemic lupus erythematosus; there is information about cases of photosensitivity reactions;
    liver and biliary tract: very rarely - impaired hepatic function; with an unknown frequency - hepatic encephalopathy (against the background of liver failure), hepatitis;
    laboratory and instrumental studies: with an unknown frequency - lengthening of the QT interval on the ECG, an increase in the concentration of uric acid and glucose (in patients with diabetes mellitus and gout, thiazide-like and thiazide diuretics should be used with caution), an increase in the activity of liver enzymes.
During clinical trials, hypokalemia with a plasma potassium content of <3.4 mmol / L was observed in 10% of patients; in 4% of patients, a decrease in the level of potassium to 3.2 mmol / L was observed after 4–6 weeks of therapy. The potassium content in blood plasma after 12 weeks decreased by an average of 0.23 mmol / L. In very rare cases, hypercalcemia has developed. With an unknown frequency, the occurrence of hypokalemia and a decrease in potassium content (which is of particular importance for patients at risk), the development of hyponatremia, accompanied by hypovolemia, orthostatic hypotension and dehydration were noted. Compensatory metabolic alkalosis may appear due to a concomitant decrease in chlorides, but its severity and frequency are insignificant.
Most of the side effects (clinical and laboratory changes) are dose-dependent.

Adverse events associated with the use of lisinopril

The most common adverse reactions are headache, dizziness, diarrhea, fatigue, nausea, and dry cough.
Possible side effects:
    immune system: infrequently - itching, skin rash; rarely - angioedema of the facial region, limbs, tongue, lips, larynx and / or epiglottis; very rarely - interstitial angioedema; with an unknown frequency - a positive test result for antinuclear antibodies, fever, eosinophilia, increased erythrocyte sedimentation rate, leukocytosis;
    blood and lymphatic system: rarely - a decrease in the content of hematocrit and hemoglobin; very rarely - thrombocytopenia, anemia, neutropenia, leukopenia, agranulocytosis; with an unknown frequency - erythrocytopenia;
    nervous system: infrequently - drowsiness, paresthesia; rarely - asthenic syndrome; with an unspecified frequency - twitching of the muscles of the face and limbs;
    psyche: infrequently - emotional lability; rarely - confusion of consciousness;
    heart: infrequently - chest pain; rarely - bradycardia, tachycardia, increased symptoms of heart failure, palpitations, myocardial infarction, atrioventricular conduction disorders;
    vessels: often - a pronounced decrease in blood pressure; rarely, orthostatic hypotension; with an unknown frequency - vasculitis;
    respiratory system: very rarely - bronchospasm; with an unknown frequency - shortness of breath;
    liver and biliary tract: very rarely - hepatitis, cholestatic and renal cell jaundice;
    gastrointestinal tract: infrequently - dysgeusia, dyspepsia, abdominal pain; rarely - xerostomia; very rarely - pancreatitis; with an unspecified frequency - decreased appetite;
    genitals and mammary gland: infrequently - decreased potency;
    skin and subcutaneous tissues: infrequently - itchy skin; rarely - alopecia, urticaria; very rarely - sweating; with an unspecified frequency - photosensitivity;
    kidneys and urinary tract: often - impaired renal function; rarely - uremia, acute renal failure; very rarely - anuria, oliguria; with an unknown frequency - proteinuria;
    musculoskeletal and connective tissue: with an unknown frequency - arthritis / arthralgia, myalgia;
    laboratory and instrumental studies: infrequently - hyponatremia, hyperkalemia; rarely - hyperbilirubinemia, increased activity of liver enzymes, increased concentration of urea and creatinine.

Overdose

Indapamide

The toxic effects of the drug when used in very high doses (up to 40 mg, i.e. 27 times higher than the therapeutic dose) were not observed.
The main symptoms of indapamide intoxication are determined, first of all, by water-electrolyte imbalance (hyponatremia, hypokalemia). Clinical manifestations of overdose: nausea, vomiting, decreased blood pressure, dizziness, convulsions, confusion, drowsiness, polyuria or oliguria, leading to anuria (due to hypovolemia).
Emergency care: elimination of indapamide from the body, intake of activated charcoal and / or gastric lavage with restoration of water and electrolyte balance.

Lisinopril

The main symptoms of an overdose of lisinopril: irritability, anxiety, drowsiness, a marked decrease in blood pressure, xerostomia, constipation, urinary retention.
Therapy: symptomatic, intravenous administration of 0.9% sodium chloride solution and vasopressors is indicated (if there are no contraindications), control of water-electrolyte balance and blood pressure. Hemodialysis may be prescribed.

Special instructions

When hospitalized, you must inform your doctor about taking Diroton Plus.
If you skip a dose, wait until your next dose at the usual time. Do not take two capsules to make up for a missed dose.

Indapamide

When prescribing thiazide-like and thiazide diuretics in patients with impaired hepatic function, hepatic encephalopathy may develop, especially in patients with electrolyte imbalance. In such cases, the use of diuretics should be discontinued.
There is information about the development of photosensitization during therapy with thiazide / thiazide-like diuretics, which requires discontinuation of Diroton Plus. If it is necessary to continue treatment, it is recommended to protect the skin from artificial UV radiation or sunlight.
Before taking Diroton Plus, it is necessary to determine the plasma sodium content in the blood. During the entire period of treatment, this parameter should be monitored regularly. All diuretics can lead to hyponatremia, which can sometimes be very serious. Constant monitoring of the plasma sodium content in the blood is required, since at the beginning of taking the drug, such a decrease in the appearance of pathological symptoms may not be accompanied. Particularly careful monitoring of sodium content should be carried out in cirrhosis of the liver and in elderly patients.
During the period of therapy, the content of potassium in the blood plasma may sharply decrease, and hypokalemia may also appear. The risk group includes debilitated and elderly patients, patients receiving combined treatment with other antiarrhythmic drugs and drugs that can lead to a prolongation of the QT interval, as well as patients with coronary and heart failure, liver cirrhosis, ascites and peripheral edema. Such patients need to minimize the likelihood of developing hypokalemia (<3.4 mmol / L).
Hypokalemia in these patients increases the risk of arrhythmias and increases the toxic effects of cardiac glycosides. Also, patients with an extended QT interval, regardless of whether they have the above conditions or the effect of drugs, should be classified as a high-risk group. Hypokalemia and bradycardia are conditions that contribute to severe arrhythmias and, in particular, abnormal heart rhythms, which can be fatal. Starting from the first week of treatment, in these groups of patients, it is necessary to regularly monitor the plasma potassium content in the blood. If hypokalemia is detected, appropriate therapy is prescribed.
There is evidence that thiazide-like / thiazide diuretics contribute to a decrease in calcium excretion by the kidneys and, as a result, lead to a temporary insignificant increase in the plasma calcium content in the blood. Hypercalcemia combined with clinical manifestations may be the result of previously undiagnosed hyperparathyroidism. In such cases, before the study of the function of the parathyroid glands, the withdrawal of diuretics is indicated.
During the period of application of Diroton Plus in patients with diabetes mellitus, it is necessary to control glucose concentrations, especially in hypokalemia.
Against the background of gout, there may be an exacerbation of the course of the disease, or an increase in the frequency of attacks.
Thiazide / thiazide-like diuretics are most effective in patients with normal or slightly reduced renal function (plasma creatinine in adults is 220 μmol / L or <25 mg / L). In elderly patients, the plasma creatinine concentration in the blood should be assessed depending on age, sex and weight.
At the beginning of therapy, due to hypovolemia, patients experience a decrease in the glomerular filtration rate, which may be associated with the loss of sodium and water ions associated with the effect of diuretics. Because of this, an increase in the plasma concentration of uric acid and creatinine in the blood is possible. In the absence of impaired renal function, such transient functional renal failure usually resolves without complications, but in the presence of impaired renal function, the general condition of patients may worsen.
It should be taken into account that against the background of the use of indapamide in athletes, a positive doping test result is possible.

Lisinopril

A significant decrease in blood pressure is most often associated with hypovolemia, which is caused by diuretics, a decrease in the amount of salt in food, dialysis, vomiting, or diarrhea. In chronic heart failure, regardless of whether it is associated with renal failure or not, arterial hypotension may occur. It was found that against the background of severe heart failure, this condition occurs more often, and this is due to the use of high doses of diuretics, impaired renal function or hyponatremia. This group of patients should be provided with medical supervision (carefully select the dose of diuretics and lisinopril). The same instructions are relevant for patients with cerebrovascular insufficiency and ischemic heart disease, in whom a sharp drop in blood pressure can cause myocardial infarction or stroke.
In the event of a significant decrease in blood pressure, the patient should take a horizontal position, possibly intravenous administration of 0.9% sodium chloride solution. Transient hypotensive reactions are not a contraindication to taking the next dose of lisinopril.
The use of lisinopril in chronic heart failure with normal / low blood pressure can lead to a decrease in blood pressure, most often this violation does not serve as a reason for canceling Diroton Plus. In cases where arterial hypotension is accompanied by clinical manifestations, the issue of dose reduction or withdrawal of lisinopril should be considered.
At the risk of developing symptomatic arterial hypotension (against the background of adherence to a low-salt / salt-free diet), regardless of the presence of hyponatremia, as well as in patients receiving high doses of diuretics, compensation for these conditions (sodium deficiency or hypovolemia) should be achieved before starting treatment.
It is necessary to control the effect of the initial dose of lisinopril on blood pressure.
Patients with acute myocardial infarction are shown standard therapy, including thrombolytics, beta-blockers, acetylsalicylic acid.
Lisinopril can be used simultaneously with nitroglycerin (intravenous or transdermal).
It is not necessary to start lisinopril therapy against the background of acute myocardial infarction and the risk of further deterioration of hemodynamics, worsening of symptoms after the appointment of vasodilators. This group of patients includes patients with systolic blood pressure ≤ 100 mm Hg. Art. and patients with cardiogenic shock. During the first three days after myocardial infarction with systolic blood pressure ≤ 120 mm Hg. Art. dose reduction is shown. With systolic blood pressure ≤ 100 mm Hg. Art. the maintenance dose is reduced to 5 mg (or temporarily to 2.5 mg). If persistent arterial hypotension is noted (with systolic blood pressure <90 mm Hg for 1 hour or longer), lisinopril is canceled.
In chronic heart failure, a significant decrease in blood pressure while using Diroton Plus can lead to an aggravation of renal dysfunction. There is evidence of cases of acute renal failure.
Against the background of the use of ACE inhibitors in patients with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney, an increase in the serum concentration of urea and creatinine in the blood was observed, most often such violations were of a temporary nature and after discontinuation of therapy were stopped. In most cases, they developed against the background of renal failure.
In acute myocardial infarction and severe renal dysfunction (with serum creatinine concentration> 177 μmol / L and / or proteinuria> 500 mg / day), lisinopril is contraindicated. If during the treatment period impairment of renal function develops (doubling of the serum creatinine concentration in comparison with the baseline value or the value of the indicator> 265 μmol / l), Diroton Plus is canceled.
During the period of lisinopril use, rare cases of angioedema of the face, extremities, tongue, lips, larynx and / or epiglottis have been recorded, which requires immediate withdrawal of lisinopril. Until the symptoms are completely resolved, the patient's condition is monitored. Most often, angioedema of the lips and face is temporary and does not require treatment, but some patients need to prescribe drugs with an antihistamine effect.
Angioedema of the larynx can be fatal. Swelling of the tongue, larynx, or epiglottis can cause secondary airway obstruction. In these cases, the immediate introduction of a solution of epinephrine 1: 1000 at a dose of 0.3–0.5 ml subcutaneously is shown; it is also necessary to ensure the patency of the airways. There is evidence that in patients of the Negroid race who received ACE inhibitors, in comparison with patients of other ethnic groups, Quincke's edema occurred more often.
With a history of Quincke's edema, not associated with the use of ACE inhibitors, the likelihood of developing angioedema during therapy with ACE inhibitors is higher.
In very rare cases, life-threatening anaphylactic reactions develop in patients taking lisinopril during desensitization with hymenoptera poison, therefore, the use of Diroton Plus is canceled before desensitization.
Also, anaphylactic reactions have occurred in patients on hemodialysis, for which dialysis membranes with high permeability were used (in particular, AN69). Such patients should use other dialysis membranes or other antihypertensive drugs.
Against the background of the use of lisinopril, a cough may develop, which should be taken into account when conducting differential diagnostics. Prolonged dry cough after discontinuation of ACE inhibitors usually stops.
The use of drugs with an antihypertensive effect during volumetric surgical interventions or during general anesthesia can lead to inhibition of the formation of angiotensin II, which is associated with compensatory renin secretion. The significant decrease in blood pressure associated with this effect can be prevented by increasing the volume of circulating blood.
Before surgery (including dental procedures), patients taking lisinopril should notify the surgeon / anesthesiologist.
There are reports of cases of hyperkalemia. The main risk factors for its development: diabetes mellitus, renal failure, the use of potassium-sparing diuretics (spironolactone, triamterene and amiloride), potassium-based salt substitutes and potassium preparations, especially against the background of impaired renal function. In cases where the simultaneous use of lisinopril with these drugs is necessary, it is necessary to regularly monitor the plasma potassium content in the blood.
During clinical studies, it was shown that with a double blockade of the RAAS (renin-angiotensin-aldosterone system) against the background of combined therapy with angiotensin II receptor antagonists, aliskiren or ACE inhibitors, in comparison with the use of only one drug that has an effect on the RAAS, there is an increase in the frequency development of such adverse events as hyperkalemia, arterial hypotension and decreased renal function (including acute renal failure). If there are absolute indications for a double blockade of the RAAS, then it should be carried out under the close supervision of a specialist with frequent monitoring of renal function, blood pressure and electrolyte content.
In patients with diabetic nephropathy, concomitant use of ACE inhibitors with angiotensin II receptor blockers should not be used.

Influence on the ability to drive vehicles and complex mechanisms

During the period of therapy, it is necessary to take into account the likelihood of developing adverse events, including dizziness, and drive vehicles with caution. It should also be borne in mind that in some patients with a decrease in blood pressure, it is possible to develop different individual reactions, especially at the beginning of treatment or when an additional antihypertensive drug is prescribed to the main treatment regimen.

Application during pregnancy and lactation

Diroton Plus is contraindicated during pregnancy / lactation.
Adequately controlled clinical studies on the use of Diroton Plus in pregnant women have not been conducted. In case of pregnancy, the drug should be stopped immediately. When planning a pregnancy, therapy should be interrupted and a doctor should be consulted to prescribe another antihypertensive drug that has an established safety profile during pregnancy.

Indapamide

Diuretics are generally contraindicated during pregnancy. In order to reduce physiological edema during pregnancy, these drugs are prohibited. Indapamide can cause fetoplacental insufficiency and intrauterine growth disorders.
Indapamide passes into breast milk.

Lisinopril

The use of ACE inhibitors in the II and III trimesters of pregnancy can lead to the death of the fetus or newborn. The condition of newborns and infants whose mothers took ACE inhibitors in the prenatal period should be carefully monitored to identify a possible significant decrease in blood pressure, the development of hyperkalemia and oliguria. Other possible violations: lack of water; in newborns - hypoplasia of the facial bones, deformation of the bones of the skull and face, impaired renal development and hypoplasia of the lungs.
Lisinopril can cross the placental barrier. Women of childbearing age need to use reliable methods of contraception. You should not start using lisinopril during pregnancy.
There is no information on the penetration of lisinopril into breast milk. If it is necessary to use Diroton Plus, breastfeeding must be interrupted.

Pediatric use

The safety profile in patients under 18 years of age has not been studied, therefore, the drug is not prescribed for this group of patients.

With impaired renal function

    severe renal failure (with creatinine clearance <30 ml / min): therapy is contraindicated;
    renal failure, renal artery stenosis in the presence of a single kidney, bilateral renal artery stenosis, condition after kidney transplantation: Diroton Plus should be used with caution.

For violations of liver function

    severe liver dysfunction or hepatic encephalopathy: therapy is contraindicated;
    hepatic impairment: Diroton Plus should be used with caution.

Use in the elderly

Diroton Plus is prescribed with caution to elderly patients.

Drug interactions

Indapamide

Unwanted combinations
With the simultaneous use of indapamide with lithium preparations, the plasma content of lithium in the blood may increase (associated with a decrease in excretion), which can cause intoxication. The combined use of diuretics with lithium preparations is possible according to indications, however, the dose of drugs must be carefully selected. It is necessary to regularly monitor the plasma lithium content in the blood.
Combinations requiring special attention
Drugs that can lead to the development of pirouette-type arrhythmias (the main risk factor is hypokalemia) include:
    some neuroleptic drugs: phenothiazines (thioridazine, cyamemazine, chlorpromazine, levomepromazine, trifluoperazine), butyrophenones (droperidol, haloperidol), benzamides (sultopride, sulpiride, amisulpride, tiapride);
    class IA and III antiarrhythmics, including hydroquinidine, quinidine, disopyramide, amiodarone, dofetilide, sotalol, ibutilide;
    other drugs: bepridil, diphemanil, cisapride, astemizole, halofantrine, moxifloxacin, mizolastine, sparfloxacin, pentamidine, erythromycin and vincamine (when administered intravenously).
Before the start of combination therapy with indapamide and the above drugs, the determination of the plasma potassium content in the blood and, if necessary, its correction is indicated. It is necessary to control the content of electrolytes in blood plasma and ECG, the clinical condition of the patient.
Patients with hypokalemia should be prescribed drugs that do not cause heart rhythm disturbances.
In patients with a reduced plasma sodium content in the blood (especially in patients with renal artery stenosis), the use of ACE inhibitors can lead to acute renal failure and / or severe arterial hypotension. With arterial hypertension and a possible decrease in the plasma sodium content in the blood in connection with the appointment of diuretics, it is recommended to adhere to one of the following recommendations:
    withdrawal of diuretics three days before starting therapy with ACE inhibitors. In the future, according to indications, the intake of diuretics can be resumed;
    the appointment of ACE inhibitors in a lower dose. If necessary, a gradual increase in dose is possible.
In chronic heart failure, ACE inhibitors should be prescribed at a lower dose, with a possible preliminary reduction in the dose of diuretics. In all cases, in the first week after starting the use of an ACE inhibitor, it is necessary to monitor renal function (plasma concentration of creatinine in the blood).
Other possible interactions:
    non-steroidal anti-inflammatory drugs (in case of systemic use), including selective inhibitors of COX-2 (cyclooxygenase-2), salicylates in high doses (from 3000 mg per day): the hypotensive effect of indapamide may decrease; against the background of significant fluid loss, acute renal failure may develop (due to a decrease in glomerular filtration); shows measures aimed at replenishing fluid loss under close control of renal function at the beginning of therapy;
    gluco- and mineralocorticosteroids (in the case of systemic use), amphotericin B (intravenous administration), tetracosactide, drugs with laxative action that stimulate intestinal motility: the likelihood of hypokalemia increases;
    baclofen: there is evidence of increased antihypertensive action; at the beginning of treatment, fluid loss should be replenished and renal function should be monitored;
    cardiac glycosides: hypokalemia may increase the toxic effects of cardiac glycosides; it is necessary to monitor the plasma potassium content in the blood, as well as the ECG. If necessary, correction of therapy is carried out.
Combinations requiring attention
    metformin: against the background of functional renal failure, which can develop with the use of diuretics, especially loop diuretics, the likelihood of lactic acidosis increases; use of metformin at a creatinine concentration> 15 mg / l in men and 12 mg / l in women (135 and 110 μmol / l, respectively) should not be used;
    spironolactone, amiloride, triamterene (potassium-sparing diuretics): in some patients, the combined use of these drugs can be effective, while taking into account the likelihood of hyperkalemia or hypokalemia (especially in diabetes mellitus and renal failure); it is necessary to control and, if necessary, correct the plasma potassium content in the blood, as well as the ECG;
    antipsychotics, tricyclic antidepressants: against the background of combined use, the antihypertensive effect of indapamide increases, and the likelihood of orthostatic hypotension increases (due to the additive effect);
    iodine-containing X-ray contrast agents: due to dehydration associated with the use of diuretics, the risk of acute renal failure may increase, especially when using high doses of iodine-containing drugs; fluid loss must be replenished prior to prescribing these funds;
    tacrolimus, cyclosporine: with an unchanged concentration of circulating cyclosporine, an increase in the plasma concentration of creatinine in the blood is possible, even with a normal sodium content in the blood plasma and the volume of circulating blood;
    calcium salts: the risk of hypercalcemia increases, which is associated with a decrease in calcium excretion by the kidneys;
    tetracosactide, corticosteroid drugs (in the case of systemic use): the antihypertensive effect is reduced (associated with sodium and fluid retention caused by corticosteroids).

Lisinopril

    diuretics: with the combined use of lisinopril with other diuretics, a significant decrease in blood pressure is noted;
    potassium-sparing diuretics (triamterene, spironolactone, amiloride), potassium preparations, potassium-containing salt substitutes: the likelihood of developing hyperkalemia increases, especially against the background of impaired renal function;
    ethanol: the effect of lisinopril is enhanced;
    nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid in a daily dose of more than 3000 mg, estrogens and adrenal stimulants: the antihypertensive effect of lisinopril is reduced;
    other drugs with hypotensive action: there is an additive effect;
    cholestyramine and antacids: gastrointestinal absorption is suppressed;
    lithium: against the background of simultaneous use with Diroton Plus, lithium excretion slows down.
The combined use of angiotensin II receptor blockers, ACE inhibitors or aliskiren for double blockade of the RAAS is not recommended, since in this case the risk of hyperkalemia, arterial hypotension and renal dysfunction (including acute renal failure) increases.

Terms and conditions of storage

Store at temperatures up to 25 ° C. Keep out of the reach of children.
Shelf life is 2 years.

Reviews about Diroton Plus

Reviews about Diroton Plus are few, usually it is recommended as an effective drug for those who are shown combination therapy in prescribed doses.

Terms of sell

You can buy Diroton Plus without a prescription.