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

(Composition of Wincote WT-01985 brown per tablet: hypromellose 2.80 mg, macrogol-400 0.45 mg, titanium dioxide 0.77 mg, talc 0.23 mg, macrogol-6000 0.27 mg, iron oxide red oxide 0.50 mg .).

Dosage 1.25 mg + 4 mg:

active substances: indapamide 1.25 mg and perindopril erbumine 4 mg;

Excipients: cellulose microcrystalline 43.425 mg, lactose monohydrate 84,60 mg, silicon dioxide colloid 0.45 mg, magnesium stearate 0.75 mg;

composition of film shell: dye Wincote WT-01097 orange 5.00 mg.

(Composition of Wincote WT-01097 orange per tablet: hypromellose 2.22 mg, macrogol-400 0.35 mg, titanium dioxide 0.61 mg, talc 0.18 mg, macrogol-6000 0.22 mg, dye sunset yellow 1.43 mg .).

Description:

Tablets 0.625 mg + 2 mg: round, biconvex tablets, film-coated, red-brown color. On the cross section, the nucleus is white or almost white in color.

Tablets of 1.25 mg + 4 mg: round, biconvex tablets, film-coated, orange. On the cross-section of the tablet the nucleus is white or almost white in color.

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

ATX: & nbsp

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

Pharmacodynamics:

Perindid is a combined preparation containing the inhibitor of angiotensin-converting enzyme (ACE) - perindopril and a thiazide-like diuretic - indapamide. The drug has antihypertensive, diuretic and vasodilating effect.

Perindid has a pronounced dose-dependent antihypertensive effect, independent of the age and position of the patient's body and not accompanied by reflex tachycardia. Does not affect the metabolism of lipids (total cholesterol, low density lipoprotein (LDL), very low density lipoproteins (VLDL), high density lipoproteins (HDL), triglycerides (TG) and carbohydrates), including those with diabetes. Reduces the risk of hypokalemia due to monotherapy with a diuretic.

The antihypertensive effect persists for 24 hours.

A stable decrease in blood pressure (BP) is achieved within 1 month against the background of Perindid without increasing the heart rate (HR).Termination of treatment does not lead to the development of the "withdrawal" syndrome.

Perindopril is an ACE inhibitor whose mechanism of action is associated with inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictive effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to the retention of sodium and liquid, does not cause reflex tachycardia in long-term treatment. The antihypertensive effect of perindopril is developed in patients with low or normal renin activity of blood plasma.

Perindopril acts via its main active metabolite, perindoprilat. Its other metabolites are inactive.

The action of Perindid leads to:

- the expansion of veins due to a change in the metabolism of prostaglandins (decreased preload on the heart);

- reduction of total peripheral resistance (OPSS) (decrease in postload on the heart).

In patients with heart failure perindopril promotes:

- decrease the filling pressure of the left and right ventricles;

- increased cardiac output and cardiac index;

- increased regional blood flow in the muscles.

Perindopril is active in arterial hypertension of any severity: mild, moderate and severe. The maximum antihypertensive effect develops in 4-6 hours after a single oral intake and persists for 24 hours.

Termination of therapy does not lead to the development of the "withdrawal" syndrome.

Has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide diuretic enhances the antihypertensive (additive) effect of perindopril.

Indapamide refers to derivatives of sulfonamide, is a thiazide diuretic. Indapamide inhibits the reabsorption of sodium in the cortical segment of the renal tubules, which increases the renal excretion of sodium and chlorine, and leads to increased diuresis. To a lesser extent increases the excretion of potassium and magnesium. Possessing the ability to selectively block "slow" calcium channels, indapamide increases the elasticity of the walls of the arteries and reduces the OPSS. Has hypotensive effect in doses that do not have a pronounced diuretic effect. An increase in the dose of indapamide does not entail an increase in the antihypertensive effect, but increases the risk of developing undesirable phenomena.

Indapamide in patients with hypertension has no effect on:

- metabolism of lipids: TG, LDL and HDL,

- metabolism of carbohydrates, even in patients with diabetes mellitus and hypertension.

Pharmacokinetics:

The combined use of perindopril and indapamide does not change their pharmacokinetic parameters as compared to the separate administration of these drugs.

Perindopril

After oral intake quickly absorbed from the gastrointestinal tract (GIT). Bioavailability is 65-70%. Eating food reduces the conversion of perindopril to perindoprilat. Half-life (T_1/2) from the blood plasma is 1 hour.

The maximum concentration in the blood plasma is achieved 3-4 hours after ingestion. Since the intake with food reduces the conversion of perindopril to perindoprilat and the bioavailability of the drug, perindopril must be taken 1 time per day in the morning, before breakfast. Taking perindopril Once a day, steady concentration is achieved within 4 days.

In the liver is metabolized with the formation of the active metabolite perindoprilata. In addition to the active metabolite perindoprilata, perindopril forms 5 more inactive metabolites. The connection with plasma proteins is dose-dependent and is 20%. Perindoprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates through the placenta and into breast milk. It is excreted by the kidneys, T_1/2 perindoprilata is about 17 hours. Do not cumulate.

In elderly patients, in patients with renal and cardiac failure, excretion of perindoprilate is slowed.

In renal failure, it is recommended to reduce the dose of perindopril, depending on the severity of renal failure (creatinine clearance (CC)).

The dialytic clearance of perindoprilat is 70 ml / min.

The kinetics of perindopril has been altered in patients with cirrhosis: the liver clearance is reduced by half. Nevertheless, the amount of perindoprilate formed does not decrease, which does not require correction of the dose.

Indapamide

Quickly and almost completely absorbed in the digestive tract. Eating somewhat slows down absorption, but does not significantly affect the amount of adsorbed indapamide. The maximum concentration in the blood plasma is achieved 1 hour after ingestion of a single dose.It binds to plasma proteins by 79%. T_1/2is from 14 to 24 hours (on average, 18 hours). Do not cumulate.

Metabolised in the liver. It is excreted by the kidneys (70%) mainly in the form of metabolites (fraction of unchanged drug is about 5%) and intestines with bile in the form of inactive metabolites (22%). In patients with renal insufficiency, the pharmacokinetic parameters of the preparation do not change significantly.

Indications:

Arterial hypertension (patients who are shown combined therapy).

Contraindications:

Perindopril

- Hypersensitivity to perindopril and other ACE inhibitors;

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

- hereditary / idiopathic angioedema;

- pregnancy (see the section "Pregnancy and the period of breastfeeding");

- the period of breastfeeding (see the section "Pregnancy and the period of breastfeeding");

- age to 18 years (efficacy and safety not established).

Indapamide

- Hypersensitivity to indapamide and other sulfonamides;

- severe hepatic insufficiency (including with encephalopathy);

- hypokalemia;

- simultaneous use with drugs that can cause arrhythmia of the "pirouette" type (see section "Interaction with other medicinal products");

- pregnancy and the period of breastfeeding (see the section "Pregnancy and the period of breastfeeding");

- age to 18 years (efficacy and safety not established).

Perindid

- Hypersensitivity to the excipients included in the preparation;

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

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

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

- simultaneous reception of drugs that extend the interval QT (see the section "Interaction with other medicinal products").

- hemodialysis (no experience of use);

- chronic heart failure (in the stage of decompensation);

- age to 18 years (efficacy and safety not established).

Carefully:

Systemic diseases of connective tissue (including systemic lupus erythematosus,scleroderma), immunosuppressant therapy (risk of developing neutropenia, agranulocytosis), oppression of bone marrow hematopoiesis, reduced circulating blood volume (diuretics, salt-free diet, vomiting, diarrhea), ischemic heart disease, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure IV functional class by classification NYHA), hyperuricemia (especially accompanied by gout and urate nephrolithiasis), lability of blood pressure, elderly age; hemodialysis using high-permeability membranes (for example, AN69®) or desensitization, low density lipoprotein apheresis (LDL), renal artery stenosis (including bilateral), condition after kidney transplantation; stenosis of the aortic valve / hypertrophic obstructive cardiomyopathy.

Pregnancy and lactation:

The use of the drug Perindid is contraindicated in pregnancy. When planning pregnancy or when diagnosing it against a background of taking the drug, stop taking the drug immediately and prescribe another antihypertensive therapy.Appropriate controlled trials of ACE inhibitors in pregnant women have not been conducted. The available limited data on the effect of the drug in the first trimester of pregnancy indicate that the drug did not lead to malformations associated with fetotoxicity. It is known that prolonged exposure to ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, delayed ossification of the skull bones) and development of complications in the newborn (such as kidney failure, arterial hypotension, hyperkalemia) . Long-term use of thiazide diuretics in the III trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and delayed fetal development. In rare cases, against the background of diuretics shortly before delivery, neonates develop hypoglycemia and thrombocytopenia.

If the patient received Perindid during the II or III trimesters of pregnancy, it is recommended to perform ultrasound examination of the fetus to assess the condition of the skull bones and kidney function.

The use of the drug Perindid is contraindicated in the period of breastfeeding. It is not known whether perindopril in breast milk.

Indapamide is excreted in breast milk. Taking thiazide diuretics causes a decrease in the amount of breast milk or suppression of lactation. In a newborn, this may lead to increased sensitivity to sulfonamide derivatives, hypokalemia and "nuclear" jaundice.

Since the use of perindopril and indapamide during lactation can cause severe complications in the infant, it is necessary to evaluate the importance of therapy for the mother and decide whether to stop breastfeeding or stop taking these medications.

Dosing and Administration:

Inside, once a day, preferably in the morning hours before breakfast, squeezed enough liquid.

The initial dose - 1 tablet Perindid (0.625 mg + 2 mg) once a day. If after 1 month of taking the drug, you can not achieve adequate control of blood pressure, the dose should be increased to 1 tablet Perindid (1.25 mg + 4 mg) once a day.

Elderly patients

The initial dose is 1 tablet of 0.625 mg + 2 mg Perindid 1 time per day.

Patients with impaired renal function

Patients with renal insufficiency (CC 60 ml / min or more) do not need dose adjustment. On the background of therapy, regular monitoring of the concentration of creatinine and potassium in the blood plasma is necessary.

For patients with KK 30-60 ml / min the maximum dose of Perindid is 0.625 mg + 2 mg once a day.

In severe violations of kidney function (QC less than 30 ml / min), therapy with Perindid is contraindicated (see section "Contraindications").

Patients with impaired hepatic function

In patients with moderate dysfunction of the liver, dose adjustments are not required.

Children and teens

Perindid should not be used in children and adolescents under 18 years of age, since efficacy and safety have not been established.

Side effects:

The incidence of adverse reactions that may occur during therapy is given in the following gradation: very often> 1/10, often> 1/100 to <1/10, infrequently from> 1/1000 to <1/100, rarely from > 1/10000 to <1/1000, very rarely from <1/10000, including individual messages, of unspecified frequency (the frequency can not be calculated from the available data).

From the side of the cardiovascular system

Infrequently: marked decrease in blood pressure, including orthostatic hypotension.

Rarely: heart rhythm disturbances, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina and myocardial infarction, possibly due to an excessive reduction in blood pressure in patients at high risk (see section "Special instructions").

On the part of the respiratory system, the organs of the thorax and the mediastinum

Often: against the background of the use of ACE inhibitors may occur a dry cough that persists long during the intake of drugs of this group and disappears after their withdrawal; dyspnea.

Infrequently: bronchospasm.

Rarely: eosinophilic pneumonia, rhinitis.

On the part of the hematopoiesis and lymphatic system

Rarely: thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.

In certain clinical situations (patients after kidney transplantation, patients on hemodialysis), ACE inhibitors can cause anemia (see section "Special instructions").

From the central and peripheral nervous system

Often: paresthesia, headache, dizziness, asthenia.

Infrequently: sleep disturbance, mood lability, increased sweating.

Rarely: confusion of consciousness.

From the digestive system

Often: dryness of the oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste, decreased appetite, indigestion, constipation, diarrhea.

Rarely: angioedema, intestinal edema, cholestatic jaundice.

Rarely: pancreatitis

Unspecified frequency: hepatic encephalopathy in patients with hepatic insufficiency (see the sections "Contraindications" and "Special instructions").

From the skin and subcutaneous fat

Often: skin rash, itching, maculopapular rash.

Infrequently: angioedema, swelling of the face, lips, extremities, tongue mucosa, folds and / or larynx; urticaria (see section "Special instructions"); reactions of hypersensitivity in patients predisposed to asthmatic and allergic reactions; hemorrhagic vasculitis.

In patients with acute form of systemic lupus erythematosus, the course of the disease may worsen.

Rarely: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

Cases of photosensitivity reaction are noted (see Fig.section "Special instructions").

From the musculoskeletal system

Often: muscle cramps.

From the urinary system

Infrequently: renal insufficiency.

Rarely: acute renal failure.

From the side of the reproductive system and mammary glands

Infrequently: impotence.

From the sense organs

Often: impaired vision, tinnitus.

Laboratory indicators

Hypokalemia; hyponatremia with hypovolemia, leading to a decrease in bcc and orthostatic hypotension; increased concentration of uric acid and glucose in blood serum; a small increase in the concentration of creatinine and urea in blood plasma, reversible after discontinuation of therapy, which often develops against the background of stenosis of the renal arteries or stenosis of the artery of a single kidney, arterial hypertension with diuretic therapy, with renal insufficiency; transient increase in sodium content in blood plasma; hypochloraemia, proteinuria.

Rarely: hypercalcemia.

Overdose:

Symptoms

The most likely symptom of an overdose is a marked decrease in blood pressure, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion and oliguria, which can go to anuria (as a result of hypovolemia).Also, electrolyte disorders (hyponatremia, hypokalemia) may occur.

Treatment

Emergency measures are reduced to excretion from the body: gastric lavage and / or the appointment of activated charcoal, followed by restoration of the water-electrolyte balance.

With a pronounced decrease in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs, if necessary, correction of hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Perindoprilat, an active metabolite of perindopril, can be removed from the body by dialysis.

Interaction:

Perindid

Unwanted combination of drugs

Lithium preparations

With simultaneous use of lithium drugs and ACE inhibitors, a reversible increase in the concentration of lithium in the blood plasma and associated toxic effects may occur. The additional administration of thiazide diuretics may further increase the concentration of lithium and increase the risk of toxicity. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended.In the case of such therapy, regular monitoring of the concentration of lithium in blood plasma (see section "Special instructions") is necessary.

A combination of drugs that requires special attention

Baclofen

Perhaps increased antihypertensive effect. It is necessary to monitor blood pressure and kidney function, if necessary, correction of the dose of antihypertensive drugs is required.

Non-steroidal anti-inflammatory drugs (NSAIDs), including high doses of acetylsalicylic acid (more than 3 g / day)

The appointment of NSAIDs may lead to a decrease in diuretic, natriuretic and antihypertensive effects. With a significant loss of fluid, as well as in elderly patients, acute renal failure may result (due to a decrease in glomerular filtration rate). Patients need to compensate for fluid loss and at the beginning of treatment regularly monitor kidney function.

A combination of funds that requires attention

Tricyclic antidepressants, antipsychotics (antipsychotics)

Preparations of these classes increase the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

Glucocorticosteroids, tetracosactide

Reduction of antihypertensive effect (fluid retention and sodium ions due to glucocorticosteroids).

Other antihypertensives: possibly increased antihypertensive effect.

Perindopril

Unwanted combination of drugs

Potassium-sparing diuretics (amiloride, spironolactone, triamterene both in monotherapy and in combination) and potassium preparations

ACE inhibitors reduce potassium-induced kidney loss caused by a diuretic. Simultaneous reception of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), preparations of potassium and potassium-containing substitutes for edible salt can lead to a significant increase in potassium in the blood serum, up to a lethal outcome. If simultaneous 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.

A combination of funds that requires special attention

Hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin

The following effects were described for captopril and enalapril. ACE inhibitors can enhance the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. The development of hypoglycemia is very rare (due to an increase in glucose tolerance and a decrease in insulin requirements).

A combination of funds that requires attention

Allopurinol, cytostatic and immunosuppressive agents, glucocorticosteroids (for systemic use), and procainamide

Simultaneous use with ACE inhibitors may be accompanied by an increased risk of leukopenia.

Means for general anesthesia

The combined use of ACE inhibitors and agents for general anesthesia can lead to an increased antihypertensive effect.

Diuretics (thiazide and "loop")

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

Preparations of gold

In the appointment of ACE inhibitors, including perindopril, patients who received infusions of gold preparations (sodium aurothiomalate) were marked with nitrate-like reactions (skin flushing, nausea, vomiting, arterial hypotension).

Indapamide

A combination of funds that requires special attention

Medicines that can cause arrhythmia such as "pirouette"

Because of the risk of developing hypokalemia, caution should be exercised while using indapamide with drugs capable of causing piruet-type arrhythmias, for example, with antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, brethil tosylate, sotalol); some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine); benzamides (amisulpride, sulpiride, sultopride, tiapride); butyrophenones (droperidol, haloperidol); other neuroleptics (pimozide); other drugs such as bepridil, disapride, difemanyl methyl sulfate, erythromycin in / in, halofantrine, misolastine, moxifloxacin, pentamidine, sparfloxacin, wincamine in / in, methadone, astemizole, terfenadine. Avoid the development of hypokalemia and, if necessary, carry out its correction; monitor the QT interval.

Medicines that can cause hypokalemia

Amphotericin B (IV), gluco- and mineralocorticosteroids (for systemic administration), tetracosactide, laxatives, stimulating the motility of the gastrointestinal tract (GIT): an increased risk of hypokalemia (additive effect). 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. You should use laxatives that do not stimulate the motility of the gastrointestinal tract.

Cardiac glycosides

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

A combination of funds that requires attention

Metformin

Functional renal failure, which can occur against the background of diuretics, especially "loop", with the simultaneous appointment of metformin increases the risk of lactic acidosis. Do not use metformin, if the creatinine concentration in the blood plasma exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

Iodine-containing contrast media

Dehydration of the body against the background of taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before using iodine-containing contrast agents, patients need to compensate for the volume of circulating blood.

Salts of calcium

With simultaneous administration, it is possible to develop hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

Cyclosporin

It is possible to increase the concentration of creatinine in the blood plasma without changing the content of circulating cyclosporine, even with a normal content of liquid and sodium ions.

Special instructions:

Lithium preparations

It is not recommended simultaneous use of the drug Perindid with lithium preparations.

Impaired renal function

Therapy with Perindid is contraindicated in patients with severe renal insufficiency (CC less than 30 ml / min). In some patients with hypertension without a previous impairment of renal function against the background of therapy with Perindid, there may be signs of acute renal failure. In this case, treatment with Perindid should be discontinued.In the future, you can resume combination therapy, using low doses of Perindid, or use drugs perindopril and indapamide in monotherapy.

Such patients need regular monitoring of potassium and creatinine in the blood serum every 2 weeks after the start of therapy and every subsequent 2 months of therapy with Perindid.

Acute renal failure often develops in patients with severe CHF or initial renal impairment, including bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.

The drug Perindid is not 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 sudden development of arterial hypotension (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 severe arterial hypotension, a 0.9% solution of sodium chloride may be required.

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 Perindid 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. As in the case of combined use of antihypertensive drugs and diuretic, regular monitoring of the potassium content in the blood plasma is necessary.

Perindopril

Neutropenia / agranulocytosis

In patients taking ACE inhibitors, there may be cases of development of neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function in the absence of other complications, neutropenia develops rarely and passes on its own after the withdrawal of ACE inhibitors.

Perindopril should be used with great care in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing impairments of kidney function. Such patients can develop severe infections that are not amenable to intensive antibiotic therapy. In the case of the appointment of perindopril, it is recommended to periodically monitor the white blood cells in the blood. The patient should be warned that in case of any signs of an infectious disease (sore throat, fever), you should immediately consult a doctor.

Hypersensitivity / angioedema (angioedema)

When taking ACE inhibitors, including 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 stopped immediately, the patient should be monitored until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually go away alone or antihistamines may be used to treat its symptoms.Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

When such symptoms occur, immediately enter subcutaneously epinephrine (adrenaline) (at 1: 1000 dilution (0.3 or 0.5 mL) and / or provide airway patency.

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.

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without a prior angioedema and with normal C1-esterase. The diagnosis is established by means of computed tomography of the abdominal cavity, ultrasound examination or at the time of surgical intervention. Symptoms disappear after stopping the intake of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors in the course of differential diagnosis, it is necessary to consider the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during desensitization procedures

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 immunotherapy with venom of Hymenoptera. 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.

Anaphylactoid reactions at an apheresis of LDL

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions in LDL-apheresis using dextran sulfate. To prevent the anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each procedure for LDL apheresis using high-flow membranes.

Hemodialysis

In patients receiving ACE inhibitors, hemodialysis using high-flow membranes (for example, AN69®) Anaphylactoid reactions were noted.Therefore, it is desirable to use a different type of membrane or use an antihypertensive drug of another pharmacotherapeutic group (see the section "With caution").

Potassium-sparing diuretics and potassium preparations

Simultaneous use of perindopril and potassium-sparing diuretics, as well as preparations of potassium and potassium-containing substitutes for edible salt is not recommended.

Cough

Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of this group. When dry cough occurs, remember the possible association of this symptom with the administration of an ACE inhibitor. If the doctor believes that therapy with an ACE inhibitor is necessary for the patient, the Perindide drug may be continued.

Children and teenagers under the age of 18

The drug Perindid is contraindicated in children and adolescents under the age of 18 due to lack of data on efficacy and safety of use.

The risk of arterial hypotension and / or renal insufficiency in patients with CHF, violation of water-electrolyte balance, etc..)

In liver cirrhosis accompanied by edema and ascites, arterial hypotension, CHF, there may be a significant activation of the renin-angiotensin-aldosterone system (RAAS),especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against a background of a salt-free diet or a long-term intake of 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 concentration of creatinine in the blood plasma, indicating the development of acute renal failure, which is more often observed with the first dose of Perindid or during the first two weeks of therapy.

Elderly patients

Before starting the Perindid preparation, you should evaluate the kidney function and the potassium content in the blood plasma. The initial dose of the drug Perindid is selected depending on the degree of BP reduction, especially with a decrease in BCC and CHF (IV functional class by classification NYHA). Such measures allow to avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, but special care should be taken when using Perindid in patients with coronary heart disease and cerebral circulatory insufficiency. In such patients, treatment should be started with a dose of 2 mg + 0.625 mg of Perindid (initial dose).

Renovascular hypertension

Treatment of Perindid with patients diagnosed or suspected renal artery stenosis should begin in a hospital with a dose of Perindid 2 mg + 0.625 mg, monitoring the function of the kidneys and the content of potassium in the blood plasma. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.

Other risk groups

In patients with CHF (IV functional class by classification NYHA) Patients with type 1 diabetes mellitus (the risk of spontaneous increase in potassium content) treatment should begin with an initial dose of 2 mg + 0.625 mg of Perindid and under medical supervision.

Patients with diabetes mellitus

When prescribing Perindid, patients with diabetes mellitus who receive hypoglycemic agents for ingestion or insulin during the first month of therapy should regularly monitor the concentration of glucose in the blood.

Ethnic Features

Perindopril (as well as other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races.

Surgical procedures / General anesthesia

The use of ACE inhibitors in patients undergoing surgery with the use of general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetics, which have an antihypertensive effect.

It is recommended to stop the use of ACE inhibitors, including perindopril, 12 hours before surgery, warning the anesthesia doctor about the use of ACE inhibitors.

Aortic stenosis / mitral Stenosis / Hypertrophic obstructive cardiomyopathy

ACE inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract.

Liver failure

In rare cases, when taking ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes fatal. The mechanism of the syndrome is unclear. When jaundice or a significant increase in activity "liver" transaminases in patients receiving an ACE inhibitor reception Perindid preparation should be discontinued.

Anemia

Anemia can develop in patients after kidney transplantation or in patients on hemodialysis.

Hyperkalemia

It can develop during treatment with ACE inhibitors, including perinoplasty. 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

Photosensitivity

There are reports of cases of increased photosensitivity against thiazide and thiazide-like diuretics. When the photosensitivity reaction develops against the background of taking Perindid, treatment should be stopped. If there is a need to resume the use of Perindid,It should protect the exposed areas of the skin from direct exposure to sunlight and artificial ultraviolet rays.

Water-electrolyte balance

The content of sodium in the blood plasma

Before the treatment with Perindid, it is necessary to determine the sodium content in the blood plasma and on the background of taking the drug to conduct regular monitoring of electrolytes in the blood plasma. All diuretics are capable of causing hyponatremia, leading to serious complications.

The content of potassium in blood plasma

Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia (less than 3.4 mmol / L) in patients: the elderly, depleted patients, patients with cirrhosis, peripheral edema, ascites, coronary heart disease, CHF. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia.

The high-risk group includes patients with an increased interval QT on the ECG.

Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias such as "pirouettes," which can be lethal.In all cases described, regular monitoring of the potassium content in the blood plasma is necessary. The first determination of the potassium content in blood plasma should be carried out within the first week after the beginning of therapy with Perindid.

Calcium in the blood plasma

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a consequence of latent hyperparathyroidism. Before the study of the function of parathyroid glands, you should abolish Perindid.

The concentration of glucose in the blood plasma

It is necessary to monitor the concentration of glucose in patients with diabetes mellitus.

Uric acid

In patients with a high concentration of uric acid in blood plasma against the background of therapy with Perindid, the frequency of exacerbation of the gout current may increase.

Diuretics and kidney function

Hypovolemia due to a decrease in bcc or hyponatremia caused by diuretics at the beginning of treatment with Perindid may lead to a decrease in the glomerular filtration rate and be accompanied by an increase in the concentration of creatinine and urea in the blood plasma.

Athletes

Indapamide can give a positive reaction during doping control.

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

Care must be taken when driving vehicles and other mechanisms that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 0.625 mg + 2 mg and 1.25 mg + 4 mg.

Packaging:

For 10 or 14 tablets in a blister of aluminum foil or aluminum foil and PVC film.

By 1, 2, 3 blisters together with instructions for use are placed in a cardboard pack.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001468

Date of registration:30.01.2012

Date of cancellation:2017-01-30

The owner of the registration certificate:Edge Pharma Private LimitedEdge Pharma Private Limited India

Manufacturer: & nbsp

EDGE PHARMA PRIVATE, Limited India

Representation: & nbspEdge Pharma Private Limited Edge Pharma Private Limited India

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Perindid (Perindid)