Perindapam - instructions for use, dose, side effects, contraindications

Excipients: Hydroxypropyl betadex 8,000 mg¹; lactose monohydrate 44.593 mg; povidone 0.407 mg; salted³ 22.375 mg; silicon dioxide 0.800 mg; silicon dioxide colloid 0,400 mg; magnesium stearate 0.800 mg.

For a dosage of 1.25 mg + 4 mg:

active ingredients: indapamide 1,250 mg and perindopril erbumine 4,000 mg²;

Excipients: hydroxypropyl betadex 16,000 mg² ; lactose monohydrate 89.187 mg; povidone 0.813 mg; salted³ 44.750 mg; silicon dioxide 1,600 mg; silicon dioxide colloid 0,800 mg; magnesium stearate 1,600 mg.

¹2 mg perindopril erbumine and 8 mg hydroxypropyl betadex are 10 mg perindopril erbumine complex and hydroxypropyl betadax with 20% perindopril erbumine content.

²4 mg perindopril erbumine and 16 mg hydroxypropyl betadex are 20 mg perindopril erbumine complex and hydroxypropyl betadax with 20% perindopril erbumine content.

³contains 98% of microcrystalline cellulose and 2% of silicon dioxide colloid.

Description:

Tablets 0.625 mg+2 mg: white, oblong, biconvex tablets with a risk on one side and with engraving "P" and "I" on different sides of the risks, the other side of the tablet is smooth.

Tablets 1.25 mg+4 mg: white, oblong, biconvex tablets with engraving "PI" on one side.

Pharmacotherapeutic group:antihypertensive agent combined (diuretic + ACE inhibitor)

ATX: & nbsp

C.09.B.A.04 Perindopril in combination with diuretics

Pharmacodynamics:

A combined preparation containing perindopril (angiotensin-converting enzyme (ACE) inhibitor) and indapamide (diuretic from the sulfonamide derivative group). The pharmacological action of the combination is due to a combination of the individual properties of each of the components (indapamide and perindopril), which in turn enhance each other's action.

In patients with hypertension, Perindapam® has a pronounced dose-dependent antihypertensive effect on both systolic and diastolic arterial pressure (BP) in the "lying" and "standing" positions. The drug lasts 24 hours. A persistent clinical effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia. The preparation Perindapam® reduces the degree of left ventricular hypertrophy, improves the elasticity of the arteries, reduces the overall peripheral vascular resistance (OPSS), does not affect the concentration of lipids (total cholesterol, high density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides) and does not affect on the metabolism of carbohydrates (including in patients with diabetes mellitus).

Perindopril - ACE inhibitor, which provides the conversion of angiotensin I into angiotensin II, which has both vasoconstrictive action and bradykinin destroying,which has a vasodilating action, to an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone, the principle of negative feedback increases the activity of renin in the blood plasma, with prolonged use reduces OPSS, which is due mainly to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by a disturbance of the water electrolyte balance or the development of reflex tachycardia. Perindopril has an antihypertensive effect in patients with both low and normal renin activity in blood plasma.

Against the background of the use of perindopril there is a decrease in both systolic and diastolic blood pressure in the "lying" and "standing" positions. Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces the degree of hypertrophy of the left ventricle.

The concomitant use of thiazide diuretics increases the severity of antihypertensive action. In addition, the combination of an ACE inhibitor and a thiazide diuretic also leads to a reduction in the risk of hypokalemia with diuretics. Perindopril normalizes the work of the heart, reducing preload and postload.

When studying hemodynamic parameters in patients with chronic heart failure, a decrease in filling pressure in the left and right ventricles of the heart, a decrease in OPSS, an increase in cardiac output and an increase in the cardiac index, and an increase in muscular regional blood flow were revealed.

Increased tolerance to physical activity (according to veloergometric test).

Indapamide belongs to the group of sulfonamide derivatives and is close to thiazide diuretics by pharmacological properties. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the Henle loop, which leads to an increase in kidney secretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, thereby increasing diuresis and antihypertensive effect.

Indapamide reduces the sensitivity of the vascular wall when exposed to adrenaline.

With an increase in the dose of thiazide diuretics, the antihypertensive effect does not increase, while the incidence of adverse reactions increases. If the effectiveness of the drug is not sufficient, do not exceed the recommended dose.

Pharmacokinetics:

The simultaneous administration of perindopril and indapamide does not affect their pharmacokinetic indices compared with the administration of these drugs alone.

Perindopril

Absorption and Metabolism

After oral administration perindopril quickly absorbed. Bioavailability is 65-70%.

Perindopril is hydrolyzed to form an active metabolite - perindoprilat, which is an ACE inhibitor. The amount of perindoprilate formed depends on the intake of food, namely the intake of perindopril during meals reduces the conversion of perindopril to perindoprilat (this effect has no significant clinical significance).

The maximum concentration (C_max) perindoprilata in the blood plasma is achieved 3-4 hours after ingestion of perindopril.

Distribution

The binding of perindoprilat to plasma proteins is less than 30% and depends on the concentration of the drug in the blood.

After repeated ingestion of a single dose of perindopril, the equilibrium concentration (C_ss) Perindoprilata is created on average on the fourth day. The effect of the drug lasts 24 hours.

Perindopril penetrates the placental barrier.

Excretion

Perindoprilat is excreted from the body by the kidneys. T_1/2 metabolite is 17 hours

Pharmacokinetics in special clinical cases

The excretion of perindoprilat is delayed in the elderly, as well as in patients with cardiac and renal insufficiency with creatinine clearance (CC) less than 60 ml / min.

The clearance of perindoprilat in dialysis is 70 ml / min.

The pharmacokinetics of perindopril changes in patients with cirrhosis of the liver: the hepatic clearance of perindopril decreases by a factor of 2. However, the concentration of perindoprilate formed does not change, and therefore, there is no need to adjust the dose of the drug.

Indapamide

Suction

Indapamide is rapidly and completely absorbed from the gastrointestinal tract (GIT). The maximum concentration (C_mOh) in the blood plasma is achieved after 1 hour after ingestion.

Distribution

Binding to blood plasma proteins - 79%. The repeated use of the drug does not lead to its cumulation in the body.

Excretion

Half-life (T_1/2) is 14-24 hours (an average of 18 hours).

It is excreted mainly by the kidneys (70% of the administered dose) and through the intestine (22%) in the form of inactive metabolites.

Pharmacokinetics in special clinical cases

The pharmacokinetics of indapamide does not change in patients with renal insufficiency.

Indications:

Essential hypertension.

Contraindications:

- Hypersensitivity to perindopril, indapamide, other ACE inhibitors, sulfonamide derivatives and excipients;

- angioedema (angioedema) in the anamnesis associated with the administration of ACE inhibitors;

- hereditary or idiopathic angioedema;

- severe renal failure (creatinine clearance (CK) less than 30 ml / min);

- severe hepatic insufficiency (including with encephalopathy);

- pregnancy;

- the period of breastfeeding;

- apheresis of low density lipoproteins (LDL) using dextran sulfate (the risk of developing hypersensitivity reactions);

- age under 18 years (effectiveness and safety not studied);

- hemodialysis or hemofiltration using some membranes with a negatively charged surface (high-flux membranes of polyacrylonitrile (the risk of developing reactions of hypersensitivity);

- use in the acute stage of myocardial infarction, chronic heart failure (IV functional class by classification NYHA), unstable angina, life-threatening ventricular arrhythmias, "pulmonary" heart;

- as in the case of other ACE inhibitors, the combined use of perindopril and aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (CC less than 60 ml / min).

- refractory hypokalemia;

- taking drugs that extend the interval QT;

- simultaneous reception with drugs that can cause arrhythmia of the "pirouette" type;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- simultaneous reception with potassium-sparing diuretics, potassium and lithium preparations and in patients with elevated potassium levels in blood plasma;

- azotemia, anuria.

Carefully:

With renal insufficiency (CC less than 60 ml / min), systemic connective tissue diseases (systemic lupus erythematosus, scleroderma), immunosuppressant therapy (risk of developing neutropenia, agranulocytosis), oppression of bone marrow hematopoiesis, decreased circulating blood volume (bcc) (taking large doses of diuretics , salt-free diet with restriction of table salt, vomiting, diarrhea, hemodialysis),coronary artery disease, cerebrovascular diseases, renovascular hypertension, diabetes mellitus with a tendency to spontaneous potassium increase, hyperuricemia (especially with accompanying gout and urate nephrolithiasis), with blood lability, or procedures for desensitization, condition after kidney transplantation, with stenosis of the aortic valve / hypertrophic obstructive cardiomyopathy, in elderly patients (over 65 years).

Pregnancy and lactation:

The use of the drug Perindapam® is contraindicated in pregnancy and breastfeeding. When planning pregnancy or when diagnosing it against a background of taking the drug, stop taking the drug immediately and prescribe another antihypertensive therapy.

Perindopril

ACE inhibitors are able to penetrate the placental barrier and lead to impaired fetal formation and development of complications in the newborn.

The effect of ACE inhibitors in the II and III trimesters of pregnancy has a toxic effect on the fetus (decreased kidney function, oligohydramnion (marked decrease in amniotic fluid volume);slowing ossification of the bones of the skull) and on the newborn (renal failure, arterial hypotension, hyperkalemia, deformities of the bones of the skull and face, and even death).

If the patient received Perindapam® during the second or third trimester of pregnancy, it is recommended to perform a newborn ultrasound to exclude arterial hypotension, oliguria, hyperkalemia, and assess the condition of the bones of the skull. Treatment oliguria should be combined with maintenance of an adequate level of a BP and renal perfusion.

There are reports of a slowdown in intrauterine development, premature birth, non-transmission of the arterial (botallova) duct, as well as fetal death while taking ACE inhibitors during pregnancy. However, it is not possible to establish exactly to what extent the prescribing of the drug played a decisive role in these situations, and in which case the accompanying disease of the mother is not possible.

If the pregnancy occurred when taking an ACE inhibitor, stop taking the drug immediately and prescribe alternative therapy, and also perform ultrasound examination of the fetal bones.

Lactation period

ACE inhibitors can be excreted in breast milk, their effect on the baby is unknown. It is recommended to stop breastfeeding while taking ACE inhibitors.

Because the indapamide, can penetrate into breast milk, and information pertaining to the penetration into breast milk of perindopril is not available, if a combination indapamide + perindopril During lactation breastfeeding should be discontinued.

Indapamide

Diuretics, including indapamide, can cause the development of placental insufficiency and a delay in intrauterine development of the fetus.

Lactation period

Indapamide is excreted in breast milk in small amounts.

Nevertheless, the use of indapamide during lactation should be avoided for the following reasons: reduction or complete suppression of milk secretion, individual undesirable effects (change in potassium content in the blood), belonging to the sulfonamide derivative group, capable of increasing the risk of allergy and "nuclear" jaundice of newborns .

Dosing and Administration:

Inside, preferably in the morning before eating, squeezed with enough liquid.

Preparation Perindapam ® take 1 tablet once a day, starting at a dosage of 2 mg + 0.625 mg.

If in a month you can not achieve adequate control of blood pressure, then the dose should be increased to 4 mg + 1.25 mg 1 time / day.

Use in elderly patients

The dose of Perindapam® is 2 mg + 0.625 mg once a day.

Before you start taking the drug you need to assess the kidney function and the content of potassium in the blood plasma. When prescribing the drug, it is worth considering the degree of BP reduction, especially in the case of dehydration and loss of electrolytes.

Application for renal failure

With SC 60 ml / min or more, dose adjustment is not required. On the background of therapy, regular monitoring of the level of creatinine and potassium in the blood plasma is necessary. For patients with moderate renal insufficiency (CK 30-60 ml / min), the maximum daily dose of Perindapam® is 2 mg + 0.625 mg (1 tablet) 1 time / day.

In some patients with hypertension without a previous obvious violation of kidney function against the background of therapy, laboratory signs of renal failure may appear. In this case, treatment should be discontinued.In the future, you can resume combination therapy, using lower doses of perindopril and indapamide, or use drugs in monotherapy.

Application for liver failure

With moderate hepatic insufficiency, dose adjustment is not required.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their developmental frequency as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000) and very rarely (<1/10000); the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

From the gastrointestinal tract

often: constipation, dryness of the oral mucosa, decreased appetite, nausea, epigastric pain, abdominal pain, changes in taste, anorexia, vomiting, indigestion, diarrhea, impaired taste;

rarely: pancreatitis, jaundice (cytolytic or cholestatic);

frequency is unknown: an increase in the activity of "hepatic" transaminases, hyperbilirubinemia, intestinal edema, with hepatic insufficiency, the development of hepatic encephalopathy is possible.

From the respiratory system

often: dry, irritating, persistent cough, passing after withdrawal of the drug, dyspnea;

infrequently: difficulty breathing, bronchospasm;

rarely: eosinophilic pneumonia, rhinitis.

From the side of the cardiovascular system

rarely: arrhythmias, incl. bradycardia, ventricular tachycardia, atrial flutter, lengthening of the interval QT, angina pectoris, myocardial infarction or stroke, possibly secondary, due to severe arterial hypotension in high-risk patients;

infrequently: excessive reduction of blood pressure, orthostatic hypotension;

frequency is unknown: Arrhythmia of the "pirouette" type (potentially fatal).

From the central nervous system and the peripheral nervous system

often: paresthesia, headache, asthenia, dizziness, vertigo, ringing in the ears, visual impairment;

infrequently: increased fatigue, mood lability, sleep disturbance, convulsions, anorexia;

rarely: confusion of consciousness;

frequency is unknown: fainting.

From the urinary system

infrequently: decreased kidney function;

rarely: proteinuria (in patients with glomerular nephropathy);

rarely: acute renal failure.

frequency unknown: a slight increase in the concentration of creatinine in urine and blood plasma (reversible after discontinuation of the drug) is most likely with stenosis of the renal arteries, the treatment of hypertension with diuretic drugs, the presence of kidney failure. It is possible (usually temporary) to increase the potassium content in the blood plasma.

From the side of the water-electrolyte balance

rarely: increase in calcium content; frequency unknown: hypokalemia is possible.

Perindopril has the ability to increase the potassium content by inhibiting the renin-angiotensin-aldosterone system, which leads to a decrease in the loss of potassium caused by indapamide. Hypokalemia with indices less than 3.4 mmol / L after 12 weeks of therapy was observed in 4% of patients taking combination perindopril and indapamide.

Possible decrease in sodium content, accompanied by hypovolemia, dehydration of the body and orthostatic arterial hypotension. Simultaneous loss of chlorine ions can lead to compensatory metabolic alkalosis (the incidence of alkalosis and its severity is low).

From the side of metabolism

frequency unknown: an increase in the concentration of uric acid and glucose in the blood serum, reversible after discontinuation of therapy.

On the part of the hematopoiesis system

rarely: hypogemoglobinemia, reduction of hematocrit;

rarely: thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (against a background of deficiency of glucose-6-phosphate dehydrogenase), anemia (in patients after kidney transplantation, hemodialysis);

frequency unknown: pancytopenia, bone marrow aplasia.

From the side of the musculoskeletal system and connective tissue

often: muscle cramps.

Allergic reactions

often: itching, rashes, maculopapular rashes;

infrequently: angioedema of the face, limbs, lips, mucous membranes, tongue, glottis and / or larynx, urticaria, skin rashes in patients predisposed to asthmatic and allergic reactions, purpura, skin rash, possibly exacerbation of systemic lupus erythematosus;

rarely: erythema multiforme, angioedema (Quincke's edema), toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity reactions.

Other:

infrequently: increased sweating, decreased potency.

Overdose:

Symptoms: marked decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to decreased circulating blood volume (BCC)); there are violations of water-electrolyte balance (low content of sodium and potassium in the blood plasma).

Treatment: gastric lavage and / or the appointment of activated charcoal, restoration of water-electrolyte balance. With a pronounced decrease in blood pressure, it is necessary to put the patient in the "lying" position on the back, raise the legs; further measures should be taken to increase the BCC (introduction of a 0.9% solution of sodium chloride in the IV).

Perindoprilat, the active metabolite of perindopril, can be eliminated from the body by dialysis.

Interaction:

Indapamide + Perindopril

Simultaneous use is contraindicated

With the simultaneous use of lithium drugs and ACE inhibitors, cases of a reversible increase in the concentration of lithium in the blood serum were recorded.

Simultaneous reception of thiazide diuretics can increase the concentration of lithium and the risk of its toxic effect against the background of an ACE inhibitor.

Simultaneous reception of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium or potassium-containing substitutes for edible salt, and the use of other drugs that increase the potassium level in the blood plasma (eg heparin), increases the risk development of hyperkalemia.

With simultaneous application, special care is required

Baclofen potentiates antihypertensive effect (requires control of blood pressure, liver function and, if necessary, dose adjustment Perindapam®).

The combination of ACE inhibitors with non-steroidal anti-inflammatory drugs (NSAIDs) (nonselective inhibitors of cyclooxygenase (COX) from the NSAID group, for example, acetylsalicylic acid in doses that have an anti-inflammatory effect - more than 300 mg / day; inhibitors of COX-2) reduces the antihypertensive effect of ACE inhibitors; increases the risk of impaired renal function, up to the development of acute renal failure; increases the potassium content in the blood serum in patients with pre-existing renal dysfunction. This combination is recommended for use with caution, especially in elderly patients.Patients should receive a sufficient amount of fluid, and also monitor the function of the kidneys before and after starting treatment with Perindapam^®.

With the use of ACE inhibitors, hypoglycemic action of insulin and hypoglycemic drugs for oral administration may be increased. The development of hypoglycemia is extremely rare (an increase in glucose tolerance and a decrease in insulin requirements).

With simultaneous application, care is required

Tricyclic antideppeccaantipsychotics (antipsychotics) increase the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

Glucocorticosteroids (GCS), tetracosactide reduce the antihypertensive effect (water and electrolyte retention due to the action of glucocorticosteroids).

When used simultaneously with other antihypertensive agents, the antihypertensive effect of Perindapam^®.

When diuretics are used in high doses, it is possible to develop hypovolemia (due to a decrease in BCC), and the addition of perindopril to a pronounced decrease in blood pressure.

With the appointment of ACE inhibitors, incl. Perindopril, nitrate-like reactions (nausea, vomiting, marked decrease in blood pressure, hyperemia of the facial skin) were noted in patients receiving gold preparations (sodium aurothiomalate) IV.

Perindopril

Simultaneous application ACE inhibitors with other agents acting on the renin-angiotensin-aldosterone system (RAAS) increases the risk of developing arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure).

Regular monitoring of blood pressure, renal function and electrolyte level in patients taking perindopril,

Simultaneous use is contraindicated

As with other ACE inhibitors, the combined use of perindopril and aliskiren in patients with diabetes mellitus or renal insufficiency (CC less than 60 ml / min).

ACE inhibitors reduce potassium-induced kidney loss caused by a diuretic. With the simultaneous use of potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) or potassium preparations with ACE inhibitors, potassium levels in the blood serum can be increased right up to a lethal outcome.If the combined use of an ACE inhibitor and the above drugs is necessary (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of potassium levels in the blood plasma and ECG parameters should be performed.

With simultaneous application, special care is required

The use of ACE inhibitors can enhance the hypoglycemic effect of hypoglycemic drugs for ingestion and insulin in patients with diabetes mellitus; when they are used simultaneously, there may be an increase in glucose tolerance, which may require correction of doses of hypoglycemic drugs for oral and insulin intake.

With simultaneous application, care is required

With the simultaneous use of allopurinol, cytostatics, immunosuppressants, GCS (for systemic use), procainamide with ACE inhibitors, an increased risk of developing leukopenia is possible.

ACE inhibitors can enhance the antihypertensive effect of some agents for general anesthesia.

The simultaneous use of diuretics in high doses can lead to hypovolemia, and the addition of perindopril to hypotension.

In the appointment of ACE inhibitors, including perindopril, patients who received gold injections (sodium aurothiomalate), nitrate-like reactions were noted (facial hyperemia, nausea, vomiting, hypotension).

Indapamide

Simultaneous use is contraindicated

Because of the risk of developing hypokalemia, simultaneous use of indapamide with drugs that cause ventricular arrhythmia such as pirouettes is counter-indicative, such as antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, brethil tosylate, sotalol), some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenes (droperidol, haloperidol), other neuroleptics (pimozide); other substances such as bepridil, cisapride, difemanyl methyl sulfate, erythromycin (w / w), halofantrine, misolastine, moxifloxacin, pentamidine, sparfloxacin, wincamine with / in application, methadone, astemizole, terfenadine. It is necessary to control the potassium content in order to avoid hypokalemia, in the course of which it is necessary to correct it, to monitor the interval QT on an electrocardiogram (ECG).

With simultaneous application, special care is required

With the simultaneous use of indapamide with amphotericin B (IV), gluco- and mineralocorticoids (for systemic administration), tetracosactide, laxatives, stimulating intestinal motility, the risk of hypokalemia (additive effect) increases. It is necessary to control the content of potassium in the blood plasma, if necessary - its correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides. Use laxatives that do not stimulate intestinal motility.

Hypokalemia increases the toxic effect of cardiac glycosides. With simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG and, if necessary, adjust the dose of cardiac glycosides.

With simultaneous application, care is required

When metformin with diuretics is used, it is possible to develop renal failure.

With simultaneous use with metformin, the risk of developing lactic acidosis increases. Do not use metformin, if the serum creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (in μMol / L) in women.

Against the background of taking diuretics, there is a decrease in BCC, the risk of developing acute renal failure increases, especially when using iodine-containing contrast media in high doses. Before using iodine-containing contrast agents, BCC should be compensated. With simultaneous application with calcium preparations, the development of hypercalcemia is possible due to a decrease in the excretion of calcium by the kidneys.

With simultaneous use with cyclosporine, the risk of kidney dysfunction (hypercreatininaemia) increases.

Special instructions:

Impaired renal function

In some patients with hypertension without a previous impairment of kidney function, the appearance of symptoms of acute renal failure may occur with the treatment with Perindapam®. In this case, treatment with Perindapam^® should be discontinued. In the future, you can resume combination therapy, using low doses of Perindapam®, or use drugs perindopril and indapamide in monotherapy.Such patients need regular monitoring of serum potassium and serum creatinine levels every 2 weeks after initiation of therapy and every subsequent 2 months of therapy with Perindapam^®. Acute renal failure often develops in patients with severe chronic heart failure or with an initial impairment of kidney function, incl. with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney. The drug Perindapam® ne recommended for patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney.

Arterial hypotension and disturbance of water-electrolyte balance

Hyponatremia is associated with a risk of a sudden drop in blood pressure (especially in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney). Therefore, when observing patients dynamically, attention should be paid to the possible symptoms of dehydration and a decrease in the electrolyte content in the blood plasma, for example, after prolonged diarrhea or vomiting. Such patients need regular monitoring of electrolytes in blood plasma.With a marked decrease in blood pressure, you may need to / in the introduction of 0.9% solution of sodium chloride.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After the recovery of bcc and blood pressure, you can resume therapy with Perindapam®, using low doses of the drug, or use drugs perindopril and indapamide in monotherapy.

The content of potassium

The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. Against the background of taking Perindapam®, you need to regularly monitor the potassium content in the blood plasma. In elderly patients or patients who are weakened, the risk of decreasing potassium levels below the permissible level (less than 3.4 mmol / l) should be considered. The same group should include patients taking several different drugs, patients with cirrhosis, which is accompanied by the appearance of edema or ascites, patients with coronary heart disease (CHD) or heart failure.Reducing the potassium content increases the toxicity of cardiac glycosides and increases the risk of arrhythmias. Low potassium, bradycardia, and an increase in the QT interval are risk factors for the development of pirouette-type arrhythmias, which can lead to death.

Before starting the drug in elderly patients, it is necessary to evaluate the functional activity of the kidneys and the content of potassium in the blood plasma. The initial dose of the drug is determined based on the degree of BP reduction, taking into account the possible dehydration and loss of electrolytes. Such measures allow to avoid a sharp decrease in blood pressure.

Perindopril

Neutropenia / agranulocytosis

The risk of developing neutropenia with the use of ACE inhibitors is dose-dependent and depends on the drug taken, the presence of concomitant diseases (renal dysfunction, especially against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), and immunosuppressant therapy. These conditions are reversible and pass after the withdrawal of ACE inhibitors.Avoiding these conditions allows strict adherence to pre-established doses. However, in the appointment of ACE inhibitors, this group of patients should carefully assess the risk / benefit ratio of the drug.

Hypersensitivity / angioedema (angioedema)

When taking ACE inhibitors, incl. perindopril, in rare cases, development of an angioedema of the face, lips, tongue, tongue of the upper palate and / or larynx can be observed. If these symptoms appear, the drug should be discontinued immediately. Patient status should be monitored until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually go away on their own or use antihistamines to treat the symptoms.

Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

When symptoms of angioedema develop, immediately enter epinephrine (epinephrine) in a dilution of 1: 1000 (0.3 or 0.5 ml) and / or provide airway patency.In the future, such patients should not be prescribed ACE inhibitors.

Patients with a history of Quincke edema who are not associated with the administration of ACE inhibitors may be at increased risk of developing it with this group of drugs.

Anaphylactoid reactions during desensitization

There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with Hepaticoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The appointment of an ACE inhibitor should be avoided for patients receiving desensitizing therapy with Hepaticoptera insect venom. Nevertheless, the development of anaphylactoid reactions can be avoided by the temporary withdrawal of the ACE inhibitor at least 24 hours before the desensitization procedure begins.

In patients with the use of ACE inhibitors and hemodialysis using high-flow membranes (for example, AN69®), anaphylactoid reactions were noted.Therefore, it is desirable to use membranes of a different type or to use an antihypertensive drug of another pharmacotherapeutic group.

In rare cases, when an apheresis of low density lipoproteins using dextran sulfate occurs in patients receiving ACE inhibitors, life-threatening anaphylactoid reactions may develop. To prevent the development of anaphylactoid reaction, the use of an ACE inhibitor should be temporarily discontinued before each apheresis session.

Cough

With the use of ACE inhibitors, it is possible to develop a dry, persistent cough. Coughing attacks are of a persistent nature, but quickly disappear after the drug is discontinued. If necessary, treatment can be continued.

Risk of arterial hypotension and / or renal failure

With cirrhosis of the liver, accompanied by edema and ascites, arterial hypotension, chronic heart failure with congestive events, significant activation of RAAS is possible, especially with pronounced hypovolemia and a decrease in the electrolytes in the blood plasma (against a background of a salt-free diet or long-term diuretics).

The use of an ACE inhibitor causes blockade of the RAAS, in this connection, a sharp decrease in blood pressure and / or an increase in the serum creatinine concentration, indicating the development of acute renal failure, is more likely to occur with the first dose of Perindapam® or during the first 2 weeks of therapy. In rare cases, this phenomenon develops sharply, the time interval between the onset of the administration of ACE inhibitors and the development of acute renal failure varies. In such cases, treatment begins with small doses with a gradual increase in the dosage of Perindapam®.

Elderly patients

In elderly patients, the function of the kidneys and the content of potassium in the blood plasma should be evaluated before starting the Perindapam® preparation. In order to prevent arterial development of hypotension, a consistent correction of the initial dose of the drug is carried out in accordance with the indices of blood pressure, especially with a decrease in BCC.

Ethnic differences

The preparation Perindapam® (like other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.

Atherosclerosis

The risk of arterial hypotension exists in all patients, but special care should be taken when used in patients with IHD and cerebral circulatory insufficiency. In such patients, treatment with Perindapam® should be started at a dose of 0.625 mg + 2 mg (initial dose). Patients with vasorenal hypertension

The use of ACE inhibitors has a beneficial effect in patients with renovascular hypertension, both awaiting surgery and when surgery is not possible. Treatment should begin with low doses of the drug, in a hospital setting, while evaluating the functional activity of the kidneys and the content of potassium in the blood plasma. Some patients may develop functional kidney failure, which quickly disappears when the drug is withdrawn.

Anemia

Anemia can be observed in patients after kidney transplantation or in patients on hemodialysis. At the same time, the lower the hemoglobin level the more, the higher was its initial level. This effect, apparently, is not dose-dependent, but may be related to the mechanism of action of ACE inhibitors.

A slight decrease in hemoglobin occurs during the first 6 months, then the hemoglobin content remains stable and completely restored after the drug is discontinued. In such patients, treatment can be continued, but a general blood test should be carried out regularly.

General anesthesia

The effect of ACE inhibitors may be accompanied by a marked decrease in blood pressure during general anesthesia, especially if the anesthetic has an antihypertensive effect. It is recommended to stop taking ACE inhibitors, incl. perindopril, two days before the surgery, warning the anesthesia doctor about the use of ACE inhibitors.

Aortic stenosis / mitral stenosis / Hypertrophic cardiomyopathy

In patients with left ventricular outflow obstruction, ACE inhibitors should be used with caution.

Patients with arterial hypertension and heart failure should not stop taking beta-blockers: ACE inhibitors can be used together with beta-blockers.

Liver failure

In rare cases, when taking ACE inhibitors, cholestatic jaundice occurs,with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of the syndrome is unclear. If there is jaundice or a significant increase in the activity of "liver" transaminases while taking ACE inhibitors, the preparation of Perindapam® should be discontinued.

Hyperkalemia

It can develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, elderly age, diabetes mellitus, some concomitant conditions (decreased BCC, acute heart failure in decompensation, metabolic acidosis), simultaneous intake of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing substitutes for edible salt and the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome. Combined use of the above drugs should be done with caution.

Indapamide

Patients with impaired hepatic function receiving indapamide could lead to the development of hepatic encephalopathy. In this case, stop taking the medication immediately.

Water-electrolyte balance

Before and during the treatment it is necessary to control the sodium content in the blood plasma. Taking any diuretic medications may reduce the sodium content in the blood plasma, in some cases without symptoms, which in turn contributes to the development of a number of serious complications. Most often control the sodium content in the blood plasma should be performed in patients at risk (eg, elderly patients or cirrhosis). Therapy thiazide and thiazide diuretics associated with the risk of hypokalemia (less than 3.4 mmol / l) in the following categories of patients at high risk: patients elderly or debilitated patients receiving concomitant drug therapy, in patients with liver cirrhosis, patients with peripheral edema, ascites, IHD, chronic heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias. High-risk group includes patients with an increased QT interval on the electrocardiogram.Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially ventricular arrhythmias such as pirouettes, which can lead to death. In all cases described, regular monitoring of the potassium content in the blood plasma is necessary. The first determination of the potassium content in the blood plasma should be carried out within the first week after the initiation of therapy with Perindapam®. If hypokalemia is detected, treatment is corrected.

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, thereby causing mild and transient hypercalcemia. Expressed hypercalcemia may be a consequence of latent hyperparathyroidism. Before examining the function of the parathyroid glands, you should discontinue taking Perindapam®.

Controlling the concentration of glucose in the blood plasma

In patients with diabetes it is necessary to constantly monitor the concentration of glucose in the blood, especially against hypokalemia.

Uric acid

In patients with a high concentration of uric acid in the blood plasma, the risk of developing gout increases.

Diuretics and kidney function

At the beginning of treatment with a diuretic drug, patients may experience a decrease in glomerular filtration rate due to hypovolemia, which in turn is caused by loss of water and sodium ions. As a consequence, the concentration of urea and creatinine can increase in blood plasma. If the kidney function is not impaired, then, as a rule, it normalizes, however, with the existing renal failure, the patient's condition may worsen.

Indapamide can give a false positive reaction when conducting a doping control, this must be taken into account when used in athletes.

Photosensitivity

There are reports of cases of increased photosensitivity against thiazide and thiazide-assisted diuretics. When the photosensitivity reaction develops against the background of taking Perindapam®, treatment should be stopped. If there is a need to restore the use of Perindapam ®, protect open areas of the body from direct exposure to sunlight and artificial ultraviolet rays.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions for the destruction of the unused Perindapam® preparation.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment with Perindapam® (especially at the beginning of the course of therapy), care should be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 0.625 mg + 2 mg and 1.25 mg + 4 mg.

Packaging:

For 7 or 10 tablets in Al/Al-baster.

For 2 blisters of 7 tablets or 3, 5 or 9 blisters of 10 tablets are placed in a cardboard box along with instructions for medical use.

Storage conditions:

In the original packaging at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002632

Date of registration:22.09.2014

Date of cancellation:2019-09-22

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Perindapam® (Perindapam®)