Perindopril PLUS Indapamide, 0.625 mg+2 mg 30 pcs

Indications

Arterial hypertension.

Active ingredient

Composition

1 tablet contains:

Active ingredients:

Indapamide 0.625 mg;

Perindopril erbumin 2 mg.

Auxiliary substances:

Cellulose microcrystalline 70.375 mg;

Corn starch pregelatinized – 15 mg;

Crospovidone – 10 mg;

Magnesium stearate – 1 mg;

Silicon dioxide colloid – 1 mg.

.

How to take, the dosage

Apply orally once daily, preferably in the morning, before breakfast, with plenty of fluid.

Doses are given for the perindopril/indapamide ratio.

The starting dose of Perindopril plus Indapamide is 0.625mg/2mg (1 tablet) once daily. If adequate BP control has not been achieved after 1 month of therapy, the dose should be increased to 1.25 mg/4mg (1 tablet) once daily.

Patients with renal insufficiency (CKD 60 ml/min or more) do not require dose adjustment. For patients with CKD 30-60 ml/min maximum dose of Perindopril plus Indapamide is 0.625mg/2mg (1 tablet) once daily, treatment should be started with selection of doses of Perindopril and Indapamide in monotherapy mode. Perindopril plus indapamide is contraindicated if CK is less than 30 ml/min (see section “Contraindications”).

Patients with moderate hepatic impairment do not require dose adjustment. Perindopril plus Indapamide is contraindicated in patients with severe hepatic impairment.

In elderly patients, the starting dose of Perindopril plus Indapamide is 0.625 mg/2 mg (1 tablet) once daily.

In elderly patients, renal function and plasma potassium should be assessed before starting Perindopril plus Indapamide. The initial dose of Perindopril plus Indapamide should be adjusted according to the degree of BP decrease, especially in decreased BOD and in chronic heart failure (functional class IV according to NYHA classification). Such measures allow to avoid sharp decrease of BP.

The risk of arterial hypotension exists in all patients, but special caution should be exercised when using Perindopril plus Indapamide in patients with CHD and insufficiency of cerebral circulation. In such patients, treatment with the drug should be started with a dose of 0.625 mg/2 mg (initial dose). In patients with diagnosed or suspected renal artery stenosis, treatment with Perindopril plus Indapamide should be started in hospital with a dose of 0.625 mg/2 mg under monitoring of renal function and plasma potassium. Some patients may develop acute renal failure, which is reversible after drug withdrawal.

In patients with chronic heart failure (functional class IV according to NYHA classification), treatment with Perindopril plus Indapamide should be started with starting dose of 0.625mg/2mg under medical monitoring.

Interaction

Combined use is not recommended

Lithium preparations: Cases of reversible increase of lithium concentration in blood serum have been reported. There is an increased risk of its toxic effects with ACE inhibitor administration.

The simultaneous use of the combination of perindopril and indapamide with lithium preparations is not recommended.

The plasma lithium concentration must be monitored if therapy is indicated.

Particular caution is required for concomitant use

Baclofen: potentiates the antihypertensive effect (requires monitoring of BP, renal function and, if necessary, adjusting the dose of Perindopril PLUS Indapamide).

The combination of ACE inhibitors with nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs,acetylsalicylic acid in doses that have anti-inflammatory effect) reduces the antihypertensive effect of ACE inhibitors; Increases the risk of renal dysfunction, up to and including acute renal failure; increases serum potassium in patients with pre-existing renal impairment.

This combination is recommended with caution, especially in elderly patients.

Patients should compensate their BOD and have their renal function monitored before and after starting treatment with Perindopril PLUS Indapamide.

Cautious use is required concomitantly

Tricyclic antidepressants, antipsychotics (neuroleptics) increase the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

Glucocorticosteroids (GCS), tetracosactide reduce the antihypertensive effect (fluid retention).

The simultaneous use with other hypotensive agents may increase the antihypertensive effect of the drug.

Perindopril

Combined use is not recommended

The ACE inhibitors reduce renal potassium loss caused by the diuretic.

When potassium-saving diuretics (spironolactone, triamterene. amiloride.eplerenone), potassium preparations or potassium-containing salt substitutes are used together with ACE inhibitors, serum potassium levels increase up to and including death.

If co-administration of ACE inhibitor and the above drugs is necessary (in case of confirmed hypokalemia), caution should be exercised and plasma potassium and ECG parameters should be monitored regularly.

The concomitant use of ACE inhibitors and angiotensin II receptor antagonists with aliskiren is contraindicated in patients with diabetes mellitus and patients with moderate renal insufficiency (CK lower than 60 ml/min).

Concomitant use with estramustine increases the risk of angioedema.

Particular caution is required during concomitant use

The use of ACE inhibitors may increase hypoglycemic effect of oral hypoglycemic agents (sulfonylurea derivatives) and insulin in diabetic patients; their combined use may increase glucose tolerance, which may require adjustment of the doses of hypoglycemic agents for oral administration and insulin.

Baclofen increases the antihypertensive effect of ACE inhibitors.

In case of concomitant use of potassium-eluting diuretics, glyptins (linagliptin, saxagliptin, sitagliptin, vildagliptin) – risk of angioedema due to inhibition of dipeptidyl peptidase IV activity by glyptin.

When used concomitantly with sympathomimetics, it enhances the antihypertensive effect of ACE inhibitors.

There are reports that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target organ damage, concurrent therapy with an ACE inhibitor and ARAII is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to use of the RAAS-acting drug alone.

Double blockade (e.g., when ACE inhibitor is combined with APAII) should be limited to individual cases with close monitoring of renal function, potassium and BP.

Cautions are required for concomitant use

The simultaneous use of allopurinol, cytostatics, immunosuppressants, GCS (for systemic use), procainamide with ACE inhibitors may increase the risk of leukopenia.

In patients whose condition requires extensive surgery or general anesthesia with drugs that cause arterial hypotension, ACE inhibitors including perindopril may block angiotensin II formation with compensatory renin release.

The day before surgery or therapy with ACE inhibitors should be discontinued.

If the ACE inhibitor cannot be discontinued, arterial hypotension developing by the described mechanism can be corrected by increasing the BOD.

Hypovolemia may occur with high-dose diuretics (due to decreased RBC), and addition of perindopril to therapy may result in marked BP reduction.

When ACE inhibitors, including perindopril, are administered to patients receiving gold (sodium aurothiomalate) intravenously, nitrate-like reactions (nausea, vomiting, marked BP reduction, facial hyperemia) have been noted.

Indapamide

Particular caution is required concomitant use

. Because of the risk of hypokalemia, indapamide should be used with caution in conjunction with drugs that cause pirouette-type ventricular arrhythmias, such as antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide ibutilide, bretylium tosylate, sotalol), some neuroleptics (chlorpromazine,cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, thiapride), butyrophenone (droperidol, haloperidol), other neuroleptics (pimozide) other substances such as bepridil, cisapride, difemanil methyl sulfate, erythromycin (IV), halofantrine, misolastin, moxifloxacin, pentamidine, sparfloxacin, vincamine when used IV, methadone, astemizole, terfenadine.

Potassium should be monitored to prevent hypokalemia, which should be corrected if this occurs, and the QT interval should be monitored on ECG.

Concomitant use of indapamide with amphotericin (IV), gluco- and mineralocorticoids (when administered systemically), tetracosactide. laxatives that stimulate gastrointestinal motility increases the risk of hypokalemia (additive effect).

Potassium content in plasma should be monitored, and if necessary – its correction.

Particular attention should be paid to patients concomitantly receiving cardiac glycosides.

Laxatives that do not stimulate gastrointestinal motility should be used.

Hypokalemia increases the toxic effects of cardiac glycosides.

In concomitant use of indapamide and cardiac glycosides, plasma potassium and ECG parameters should be monitored and, if necessary, the dose of cardiac glycosides should be adjusted.

Consideration is required with concomitant use

When using metformin with diuretics, renal failure may occur.

Concomitant use with metformin increases the risk of lactic acidosis.

Do not use metformin if serum creatinine concentration exceeds 15 mg/L in men and 12 mg/L in women.

The use of diuretics decreases the BOD and increases the risk of acute renal failure, especially with the use of iodine-containing contrast agents in high doses.

Before the use of iodine-containing contrast agents, the BOD should be compensated.

In concomitant use with calcium preparations hypercalcemia may occur due to reduced renal calcium excretion.

Simultaneous use with cyclosporine increases the risk of renal dysfunction (hypercreatininemia).

Special Instructions

It is not recommended to use the drug concomitantly with lithium preparations.

Perindopril PLUS Indapamide therapy is contraindicated in patients with severe renal impairment (CK values less than 30 ml/min).

In some patients with arterial hypertension without previous renal dysfunction during therapy with the drug, symptoms of acute renal failure may occur. In this case, treatment with this drug should be discontinued. In the future, combined therapy using low doses of Perindopril PLUS Indapamide may be resumed, or Perindopril and Indapamide may be used in monotherapy. Such patients require regular monitoring of serum potassium and creatinine every 2 weeks after therapy initiation and every 2 months thereafter with Perindopril PLUS Indapamide.

Acute renal failure is more likely to develop in patients with severe chronic heart failure or underlying renal dysfunction, including bilateral renal artery stenosis or artery stenosis of the only functioning kidney.

The drug is not recommended for patients with bilateral renal artery stenosis or artery stenosis of the only functioning kidney.Hyponatremia is associated with the risk of sudden BP decrease (especially in patients with bilateral renal artery stenosis or artery stenosis of the only functioning kidney). Therefore, during the dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and decreased plasma electrolyte content, for example, after prolonged diarrhea or vomiting. These patients require regular monitoring of plasma electrolytes.

In case of marked BP decrease, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After restoration of the RBC and BP, therapy with Perindopril PLUS Indapamide may be resumed using low doses of the drug, or using Perindopril and Indapamide in monotherapy.Combined use of Perindopril and Indapamide does not prevent development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. As in case of combined use of hypotensive agents and a diuretic, regular monitoring of plasma potassium is necessary.

Perindopril

In patients taking ACE inhibitors there may be cases of neutropenia/agranulocytosis, thrombocytopenia and anemia.

In patients with normal renal function in the absence of other complications neutropenia is rare and resolves itself after withdrawal of ACE inhibitors.

Perindopril should be used with extreme caution in patients with connective tissue disease concomitantly receiving immunosuppressive therapy, allopurinol or procainamide, especially in existing renal impairment. These patients may develop a severe infection that is not amenable to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that in case of any signs of infectious disease (sore throat, fever) it is necessary to immediately consult a physician.

In rare cases, when taking ACE inhibitors, including perindopril, the development of angioedema of the face, lips, tongue, uvula, and/or larynx may be observed. If these symptoms occur, the drug should be discontinued immediately. The patient should be monitored until the signs of edema have completely disappeared.

If only the face and lips are affected, angioedema usually resolves on its own or antihistamines may be used to treat the symptoms. Angioedema accompanied by swelling of the tongue or larynx may result in airway obstruction and could be fatal.

In case of symptoms of angioedema, epinephrine (adrenaline) in 1:1000 dilution (0.3 or 0.5 ml) should be immediately administered subcutaneously and/or airway patency should be provided.Patients with a history of Quincke’s edema not associated with taking ACE inhibitors may be at increased risk of developing it when taking this group of drugs.

Patients of Negro race develop angioedema more frequently than patients of other races.In rare cases, angioedema of intestine develops during therapy with ACE inhibitors. Patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without preceding angioedema of the face and with normal C-1 esterase levels.

The diagnosis is established by abdominal computed tomography, ultrasound, or at the time of surgery. Symptoms disappear after discontinuation of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, when making a differential diagnosis, it is necessary to consider the possibility of developing angioedema of the intestine. There are separate reports on the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy with venom of hymenopteran insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures.

The use of ACE inhibitor should be avoided in patients receiving immunotherapy with venom of hymenopterous insects. However, the development of anaphylactoid reactions can be avoided by temporarily withdrawing the ACE inhibitor at least 24 hours before the desensitization procedure.

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

In patients receiving ACE inhibitors, anaphylactoid reactions have been noted during hemodialysis with high-flow membranes (e.g., AN69R). Therefore, it is advisable to use a different type of membrane or to use a hypotensive drug from a different pharmacotherapeutic group.

Dry cough may occur against the background of ACE inhibitor therapy, which disappears after discontinuation of drugs of this group. If dry cough occurs, remember that this symptom may be associated with ACE inhibitor therapy. If the physician considers that therapy with an ACE inhibitor is necessary for the patient, Perindopril PLUS Indapamide may be continued.

In cirrhosis with edema and ascites, arterial hypotension, chronic heart failure, significant activation of renin-angiotensin-aldosterone system (RAAS) is possible, especially with significant hypovolemia and decrease of electrolytes in blood plasma (against a salt-free diet or long-term use of diuretics).

The use of ACE inhibitor causes RAAS blockade, due to this a sharp decrease of BP and/or increase in serum creatinine is possible, indicating the development of acute renal failure, which is often observed with the first dose of Perindopril PLUS Indapamide or during the first 2 weeks of therapy.

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be monitored regularly during the first month of therapy.Perindopril (like other ACE inhibitors) has less pronounced antihypertensive effect in patients of non-human race compared to other races.

The use of ACE inhibitors in patients undergoing surgery with general anesthesia may result in a significant decrease in BP, especially with the use of general anesthesia agents that have antihypertensive effects.

The use of ACE inhibitors, including perindopril, should be discontinued 12 hours before the surgical intervention, and the anesthesiologist should be informed about the use of ACE inhibitors.

ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and with aortic and/or mitral stenosis and GOCMP (hypertrophic obstructive cardiomyopathy).In rare cases, against the background of ACE inhibitors cholestatic jaundice occurs, with progression which develops fulminant liver necrosis, sometimes with a fatal outcome. If jaundice or significant increase in “hepatic” transaminases activity occurs while taking ACE inhibitors, Perindopril PLUSindapamide should be discontinued.

In patients after kidney transplantation or in patients undergoing hemodialysis, anemia may develop.During treatment with ACE inhibitors, including perindopril, hyperkalemia may develop. The risk factors of hyperkalemia are renal insufficiency, elderly age, diabetes mellitus, some concomitant conditions (decreased BOD, acute decompensated heart failure, metabolic acidosis), concomitant use of potassium-saving diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing salt substitutes and other drugs that increase plasma potassium content (eg, heparin). Hyperkalemia can lead to serious cardiac rhythm disturbances, sometimes fatal. Combined use of the above drugs is not recommended; if necessary, the therapy should be conducted with extreme caution.

Indapamide

There have been reports of photosensitivity with thiazide and thiazide-like diuretics. If photosensitivity reaction develops with Perindopril PLUS Indapamide, treatment should be discontinued. If it is necessary to resume the use of the drug, exposed skin should be protected from direct sunlight and artificial ultraviolet rays and sun exposure should be avoided.

Perindopril PLUS Indapamide treatment should be preceded by plasma sodium determination and regular monitoring of plasma electrolytes (especially in elderly patients). All diuretics may cause hyponatremia leading to serious complications. therapy with thiazide and thiazide-like diuretics is connected with risk of hypokalemia (less than 3.4 mmol/l) in elderly patients, depressed patients, patients with liver cirrhosis, patients with peripheral edema, ascites, IBS, chronic heart failure.

Hypokalemia in these patients increases the toxic effects of cardiac glycosides and increases the risk of arrhythmias. Patients with prolonged QT interval on ECG are at increased risk. Hypokalemia, as well as bradycardia, contributes to the development of severe heart rhythm disturbances, especially ventricular pirouette arrhythmia, which may be fatal. In all the described cases, regular monitoring of plasma potassium content is necessary. The first determination of plasma potassium content should be made within the first week after the beginning of therapy with the drug.

Thiazide and thiazide-like diuretics decrease renal excretion of calcium, leading to a slight and temporary increase in plasma calcium. Severe hypercalcemia may result from occult hyperparathyroidism. Perindopril PLUS Indapamide should be discontinued before parathyroid function study.Glucose concentration should be controlled in patients with diabetes mellitus.

Patients with elevated plasma concentrations of uric acid during therapy may have increased incidence of gout exacerbation.

Hypovolemia as a result of decreased RBC or hyponatremia caused by taking diuretics at the start of drug therapy may lead to decreased glomerular filtration rate and be accompanied by increased plasma creatinine and urea.

Indapamide may give false positives in doping controls.

Pediatric use

Perindopril PLUS Indapamide is contraindicated in children and adolescents less than 18 years of age due to lack of data on its effectiveness and safety.

Effects on driving and operating machinery

Perindapamide should be used with caution when driving motor vehicles and other technical devices requiring increased attention and rapid psychomotor reactions (risk of dizziness, syncope).

Contraindications

Hypersensitivity to excipients in the drug;

Severe renal insufficiency (CK < 30 ml/min);

Concurrent use with potassium-saving diuretics, potassium and lithium preparations, and in patients with hyperkalemia;

Concomitant use of QT interval prolonging drugs;

Perindopril plus Indapamide should not be used in patients on hemodialysis or in patients with untreated decompensated heart failure because of insufficient clinical experience;

Age

Side effects

Classification of the frequency of side effects (WHO): very common (>1/10). common (>1/100 to < 1/10), infrequent (>1/1000 to < 1/100), rare (>1/10 000 to < 1/1000). Very rare (<1/10,000), frequency unknown (frequency cannot be calculated from available data).

Hematopoietic system side: infrequent – eosinophilia, hyponatremia, very rare – thrombocytopenia, leukopeia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (patients after kidney transplantation, patients on hemodialysis) ACE inhibitors may cause anemia.

CNS side:often – paresthesia, headache, dizziness, vertigo; infrequently – sleep disturbance, mood swings; very rarely – confusion; frequency unknown – fainting.

Visual organ:often – visual impairment.

Hearing organ:often – tinnitus.

Cardiovascular system disorders: infrequent – marked decrease in BP (including orthostatic hypotension), palpitations; very rare – cardiac rhythm disorders (including bradycardia, ventricular tachycardia, atrial fibrillation), angina pectoris and myocardial infarction, possibly due to excessive pressure drop in high risk patients; frequency is unknown – “pirouette”-type arrhythmias (possibly fatal), QT interval prolongation on ECG.

In the respiratory system:often – dry cough may occur with ACE inhibitors, which is prolonged while taking this group of drugs and disappears after their withdrawal, shortness of breath; rarely – bronchospasm; very rarely – eosiophilic pneumonia, rhinitis.

In the digestive system:often – dry mucous membrane of the mouth, nausea, vomiting, abdominal pain, pain in the epigastrium, impaired sense of taste, decreased appetite, dyspepsia, constipation, diarrhea: very rare – pancreatitis, angioneurotic edema of the intestine, cholestatic jaundice; frequency unknown – hepatic encephalopathy in patients with liver failure, increased activity of “liver “transaminases.

Skin disorders:frequently – skin rash, itching, maculopapular rash; infrequently – angioedema of face, lips, extremities, mucous membrane of tongue, vocal folds and/or larynx, urticaria, hypersensitivity reactions in patients predisposed to bronchoconstrictive and allergic reactions, hemorrhagic vasculitis. In patients with acute systemic lupus erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome may worsen the course of the disease. There have been cases of photosensitivity reactions.

Muscular system disorders:often – muscle spasms.

Since the urinary system: infrequent – renal failure; very rare – acute renal failure, frequency unknown – hepatitis.

Concerning the reproductive system: infrequent – erectile dysfunction.

Laboratory findings: rarely – hypercalcemia; frequency unknown – hypokatemia, especially significant in patients at risk; hyponatremia and gynovolemia, leading to dehydration and orthostatic hypotension; increased uric acid and blood glucose concentrations during drug administration: slight increase in creatinine concentration in urine and plasma, passing after discontinuation of therapy, more often in patients with renal artery stenosis, during treatment of arterial hypertension with diuretics and in cases of renal insufficiency; hyperkalemia, more often transient.

Others:often, asthenia; infrequently, increased sweating.

In the use of ACE inhibitors, a syndrome of impaired secretion of aitydiuretic hormone has rarely been observed.

Similarities