Co-Perineva, tablets 1, 25+4 mg 90 pcs

hypotensive combination drug (diuretic + angiotensin-converting enzyme inhibitor)

Indications

Essential hypertension.

Active ingredient

Composition

for 1 tablet 0.625 mg + 2 mg/1.25 mg + 4 mg/2.5 mg + 8 mg

Active ingredients:

Indapamide 0.625 mg/1.250 mg/2.500 mg

Perindopril erbumin K, semifinished pellets 37.515 mg/75.030 mg/150.060 mg

[Active substance of semifinished pellets:

Perindopril erbumin 2,000 mg/4,000 mg/8,000 mg

Ancillary substances of the semi-finished granules: calcium chloride hexahydrate, lactose monohydrate, crospovidone]

Excipients: microcrystalline cellulose, sodium hydrocarbonate, colloidal silicon dioxide, magnesium stearate

Ili

for 1 tablet 0.625 mg + 2 mg/1.25 mg + 4 mg/2.5 mg + 8 mg

Active ingredients:

Indapamide 0.625 mg/1.250 mg/2.500 mg

Perindopril erbumin 2.000 mg/4.000 mg/8.000 mg

Supporting substances: calcium chloride hexahydrate, lactose monohydrate, crosspovidone, microcrystalline cellulose, sodium hydrocarbonate, colloidal silicon dioxide, magnesium stearate

How to take, the dosage

Orally, once a day, preferably in the morning before breakfast, with plenty of fluid.

If possible, Co-Perineva® should be started with single-component doses. If clinically necessary, the combined therapy with Co-Perineva® may be used immediately after monotherapy with one of its components (perindopril and indapamide).

Doses are given for the indapamide/perindapamil ratio.

The initial dose is 1 tablet of Co-Perineva® (0.625 mg + 2 mg) once daily. If adequate BP control is not achieved after 1 month of therapy, the dose should be increased to 1 tablet of Co-Perineva® (1.25 mg + 4 mg) once daily.

If necessary to achieve a more significant antihypertensive effect, the dose can be increased to maximum daily dose of Co-Perineva® – 1 tablet (2.5 mg + 8 mg) once daily.

Elderly patients

The starting dose is 1 0.625 mg tablet + 2 mg of Co-Perineva® once daily. The drug therapy should be started under control of renal function and BP.

Patients with impaired renal function

The drug Co-Perineva® is contraindicated in patients with severe renal failure (CK less than 30 ml/min) (see section “Contraindications”).

Patients with moderate renal impairment (CKR 30-60 ml/min) are recommended to start therapy with the required doses of drugs (in monotherapy) included in Co-Perineva®.

Maximum daily dose of Co-Perineva® -1.25 mg + 4 mg.

Patients with CK³ 60 ml/min do not need dose adjustment. Creatinine and serum potassium concentrations should be monitored regularly during the therapy.

Patients with impaired liver function

The drug is contraindicated in patients with severe hepatic insufficiency (see section “Contraindications”).

Dose adjustment is not required in mild hepatic insufficiency.

Children and adolescents

The drug Co-Perineva® should not be used in children and adolescents under 18 years of age because there is insufficient data on efficacy and safety (see Section “Contraindications”).

Interaction

General drug interactions for perindopril and indapamide

Simultaneous use is not recommended

Lithium preparations: Concomitant use of lithium drugs and ACE inhibitors has reported cases of reversible increases in plasma lithium and associated toxic effects. Concomitant use of thiazide diuretics may further increase the lithium content in blood plasma and increase the risk of its toxic effects against the background of ACE inhibitor use.

Simultaneous use of Co-Perineva® with lithium preparations is not recommended. If concomitant use is necessary, the lithium content in the blood plasma should be monitored carefully (see section “Special Precautions”).

Simultaneous use of drugs requiring special attention and caution

Baclofen: possible increased antihypertensive effects. BP, renal function control and, if necessary, adjustment of the dose of hypotensive agents are necessary.

NSAIDs, including high doses of acetylsalicylic acid (³ 3 g/day): .concomitant use of ACE inhibitors and NSAIDs (including acetylsalicylic acid in doses with anti-inflammatory activity, cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs) may decrease the antihypertensive effect of ACE inhibitors and increase the risk of renal impairment up to development of ARF, increases serum potassium, especially in patients with initially decreased renal function.

Caution should be exercised when using this combination, especially in elderly patients. Patients should compensate fluid loss before the start of treatment and monitor renal function regularly both at the beginning of therapy and during treatment.

Single use requiring attention

Tricyclic antidepressants, antipsychotics (neuroleptics):Drugs in these classes increase antihypertensive effects and increase the risk of orthostatic hypotension (additive effect).

Drug interactions for andndapamide

Single use requiring special attention and caution

Drugs that can cause pirouette-type ventricular polymorphic tachycardia: because. there is a risk of hypokalemia, indapamide should be used with caution concomitantly with medications capable of inducing pirouette-type ventricular tachycardia such as class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, dofetilide, ibutilide, brettilia tozilate, sotalol), some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, thiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide) other drugs such as bepridil, cisapride, difemanil methyl sulfate, IV erythromycin, halofantrine, misolastin, moxifloxacin, pentamidine, sparfloxacin, IV vincamine, methadone, astemizole, terfenadine. It is necessary to monitor the serum potassium content in order to avoid hypokalemia, in case of which it is necessary to correct it, monitor the QT interval on ECG.

Drugs that may cause hypokalemia: amphotericin B when administered intravenously, gluco- and mineralocorticoids (when administered systemically), tetracosactide, and laxatives that stimulate intestinal motility contribute to the risk of hypokalemia (additive effect). Control of plasma potassium is necessary, and its correction if necessary. Particular attention should be paid to patients concomitantly receiving cardiac glycosides. Laxatives should be used which do not stimulate intestinal motility.

Hypokalemia increases toxic effects of cardiac glycosides. When concomitant use of indapamide and cardiac glycosides, plasma potassium and ECG parameters should be monitored and the dose of cardiac glycosides should be adjusted if necessary.

Simultaneous use requiring attention

Kaliesaving diuretics (amiloride, spironolactone, triamterene):this combination is reasonably used in some patients. Hypokalemia or hyperkalemia may be observed (especially in patients with renal insufficiency or DM). If concomitant use of indapamide and potassium-saving diuretics is necessary, plasma potassium and ECG parameters should be monitored. If necessary, the treatment regimen may be revised.

Metformin:functional renal insufficiency against the background of diuretics, especially “loop” diuretics, simultaneous use with metformin increases the risk of lactic acidosis. Metformin should not be used if plasma creatinine concentration exceeds 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.

Iodine-containing contrast agents: patients with hypovolemia on therapy with diuretics have an increased risk of developing ARF, especially when using contrast agents containing high doses of iodine. Before the use of iodine-containing contrast agents the BOD should be replenished.

Calcium salt preparations: when used concomitantly, hypercalcemia may develop due to decreased calcium excretion by the kidneys.

Cyclosporine, tacrolimus: Possible increase of creatinine concentration in plasma without changing cyclosporine concentration in plasma even in the presence of marked sodium ion loss and dehydration.

Glucocorticosteroids (GCS), tetracosactide (when used systemically): reduction of antihypertensive effect (fluid and sodium ion retention due to GCS action).

Drug interactions for perindopril

The data from clinical studies show that dual RAAS blockade resulting from concomitant administration of ACE inhibitors, ARA II or aliskiren leads to an increased incidence of adverse events such as arterial hypotension, hyperkalemia and renal function impairment (including ARF), compared to situations where only one RAAS-acting drug is used (see See Sections “Pharmacological Properties. Pharmacodynamics”, “Contraindications” and “Special Indications”).

Drugs that cause hyperkalemia

Some drugs or classes of drugs may increase the incidence of hyperkalemia: Aliskiren, potassium salts, potassium-saving diuretics, ACE inhibitors, ARA II, NSAIDs, heparins, immunosuppressants (such as cyclosporine or tacrolimus), drugs containing trimethoprim, including a fixed combination of trimethoprim and sulfometoxazole.

The combination of these drugs increases the risk of hyperkalemia.

Simultaneous use is contraindicated

Aliskiren and medicinal products containing aliskiren: The concomitant use of ACE inhibitors with aliskiren or drugs containing aliskiren in patients with DMi and/or with moderate to severe impaired renal function (FFR < 60 ml/min/1.73 m2 body surface area) is contraindicated (see contraindications).

The risk of hyperkalemia, impaired renal function, cardiovascular morbidity and mortality increases.

Extracorporeal therapy:Methods of extracorporeal therapy that bring blood into contact with negatively charged surfaces, such as hemodialysis or hemofiltration using high-flow membranes (such as polyacrylonitrile membranes) and LDL apheresis using dextran sulfate are contraindicated due to the increased risk of anaphylactoid reactions. If such treatment is necessary, use another type of membrane or use a hypotensive drug of another pharmacotherapeutic group.

Neutral endopeptidase inhibitors: The simultaneous use of ACE inhibitors with the medicinal products containing sacubitril (neprilysin inhibitor) increases the risk of angioedema, therefore simultaneous use of these drugs is contraindicated. ACE inhibitors should be administered not earlier than 36 hours after withdrawal of drugs containing Sacubitril. Administration of agents containing Sacubitril is contraindicated in patients receiving ACE inhibitors and also within 36 hours after cancellation of ACE inhibitors.

Simultaneous use is not recommended

Aliskiren: in patients without DM or impaired renal function (GFR < 60 ml/min/1.73 m2 body surface area), increased risk of hyperkalemia, impaired renal function and increased cardiovascular morbidity and mortality (see “Special Instructions”).

Simultaneous use of ACE inhibitors and ARA II: In patients with established atherosclerotic disease, heart failure, or DM with target organ damage, concomitant use of ACE inhibitors and ARA II has been reported in the literature to increase the incidence of arterial hypotension, syncope, hyperkalemia, and renal function impairment (including ARF), compared with situations in which only one RAAS-acting drug is used. The use of dual RAAS blockade (e.g., concomitant use of ACE inhibitors and ARA II) should be limited to single cases with strict monitoring of renal function, plasma potassium (see section “Special Precautions”).

Estramustine: Concurrent use may increase the risk of side effects such as angioedema.

Kalium-saving diuretics (spironolactone, triamterene), potassium preparations or potassium-containing salt substitutes:Serum potassium is usually within normal limits, but hyperkalemia may occur in some patients taking perindopril. Potassium-saving diuretics (e.g., spironolactone, triamterene or amiloride), potassium preparations or potassium-containing salt substitutes may lead to a significant increase in serum potassium. Caution should also be exercised when using perindopril concomitantly with other drugs that increase serum potassium levels, such as trimethoprim and co-trimoxazole (trimethoprim + sulfamethoxazole), because it is known that trimethoprim acts similarly to the potassium-saving diuretic amiloride. Therefore, concomitant use of perindopril with the above drugs is not recommended. If simultaneous use is necessary due to hypokalemia, caution should be exercised and serum potassium and ECG should be monitored regularly.

Co-trimoxazole (trimethoprim + sulfamethoxazole): Simultaneous use with ACE inhibitors may increase the risk of hyperkalemia.

Simultaneous use requiring special attention

Hypoglycemic oral agents (sulfonylurea derivatives) and insulin: Epidemiologic studies have shown that coadministration of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) may increase the hypoglycemic effect of insulin and oral hypoglycemic agents to the point of developing hypoglycemia. This effect is likely to be observed during the first weeks of concomitant therapy as well as in patients with impaired renal function.

Kalinergic diuretics: Patients receiving diuretics, especially those with hypovolemia and/or reduced salt concentrations, may experience a pronounced decrease in BP at the start of therapy with ACE inhibitors. The risk of arterial hypotension can be reduced by withdrawal of the diuretic, replenishment of fluid or salt loss before initiating perindopril therapy, as well as by administration of low dose perindopril with its further gradual increase.

In patients with arterial hypertension with hypovolemia or reduced salt concentration during diuretic therapy, the diuretic should be stopped before starting the ACE inhibitor (and the potassium-sparing diuretic may be prescribed again later), or the ACE inhibitor should be prescribed at a low dose with its further gradual increase.

When using diuretics in patients with CHF, the ACE inhibitor should be prescribed at a very low dose, possibly after reducing the dose of a concomitantly used potassium-saving diuretic.

In all cases during the first weeks of ACE inhibitor therapy, renal function (plasma creatinine concentration) should be monitored.

Kaliesaving diuretics (eplerenone, spironolactone):when using eplerenone or spironolactone in doses of 12.5 mg to 50 mg per day and low doses of ACE inhibitors in the therapy of CHF II-IV functional class according to the NYHA classification with left ventricular ejection fraction < 40% and previously used ACE inhibitors and loop diuretics there is a risk of hyperkalemia (with possible death), especially if the recommendations regarding the use of this drug combination are not followed.

Before using this combination of drugs, make sure there is no hyperkalemia or renal dysfunction.

It is recommended to monitor creatinine concentration and plasma potassium regularly: weekly during the first month of treatment and monthly thereafter.

Racecadotril: an increased risk of angioedema has been reported with concomitant use of ACE inhibitors and racecadotril (an enkephalinase inhibitor).

MTOR inhibitors (eg, sirolimus, everolimus, temsirolimus): When used concomitantly with mTOR inhibitors, therapy may be accompanied by an increased risk of angioedema.

Tissue plasminogen activators: In observational studies, an increased incidence of angioedema was found in patients taking ACE inhibitors after using alteplase for thrombolytic therapy of ischemic stroke.

Simultaneous use requiring attention

Hypotensive agents and vasodilators: Simultaneous use of these drugs may enhance the antihypertensive effects of perindopril. When concomitant use with nitroglycerin, other nitrates or other vasodilators additional BP decrease is possible.

Allopurinol, cytostatic and immunosuppressive agents, GCS (in systemic use) and procainamide: Simultaneous use with ACE inhibitors may increase the risk of leukopenia.

General anesthetic agents: The use of ACE inhibitors may increase the hypotensive effect of some general anesthetic agents.

Gold products:Accompanied by the use of ACE inhibitors including perindopril and the intravenous administration of gold (sodium aurothiomalate) a symptom complex including facial hyperemia, nausea, vomiting and a marked decrease in BP has been described.

Glyptins (linagliptin, saxagliptin, sitagliptin, vildagliptin): The risk of angioedema due to suppression of dipeptidyl peptidase-4 (DPP-4) activity by glyptin increases when used concomitantly with ACE inhibitors.

Sympathomimetics: may attenuate the antihypertensive effect of ACE inhibitors.

Cyclosporine: simultaneous use with ACE inhibitors may increase the risk of hyperkalemia. It is recommended to control the serum potassium content.

Heparin: Simultaneous use with ACE inhibitors may increase the risk of hyperkalemia. It is recommended to monitor serum potassium.

Special Instructions

Systemic connective tissue diseases (including systemic lupus erythematosus (SLE), scleroderma), immunosuppressant therapy (risk of neutropenia, agranulocytosis), bone marrow inhibition, decreased circulating blood volume (CBC) (diuretics, diet with restriction of table salt, vomiting, diarrhea, hemodialysis), ischemic heart disease, cerebrovascular disease, hepatic and renal function disorders, renovascular hypertension, DM, chronic heart failure (CHF) (functional class IV according to NYHA classification), hyperuricemia (especially accompanied with gout and urate nephrolithiasis), BP lability, use in elderly patients, black race, athletes (positive reaction is possible at doping control), concomitant desensitization therapy with allergens (e.g., Hymenopteran venom), post kidney transplantation conditions, aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy (HACMI), atherosclerosis, bilateral renal artery stenosis, presence of only one functioning kidney, concomitant therapy with potassium-saving diuretics, potassium preparations or in patients with elevated plasma potassium levels, concomitant use with lithium, gold, nonsteroidal anti-inflammatory drugs (NSAIDs), baclofen, corticosteroids, drugs that may cause QT interval prolongation, drugs that may cause pirouette-type polymorphic ventricular tachycardia, except non antiarrhythmic medications (see See Contraindications).

The drug Co-Perineva® should not be used in children and adolescents under 18 years of age because data on efficacy and safety are insufficient.

Elderly patients

Before starting Co-Perineva®, renal function and plasma potassium should be evaluated. The starting dose of Co-Perineva® should be adjusted according to the degree of BP decrease, especially in case of decreased BCC and electrolyte loss. Such measures allow to avoid a sharp decrease of BP.

The initial dose is 1 tablet of 0.625 mg + 2 mg of Co-Perineva® once daily. The drug therapy should be started under control of renal function and BP.

Patients with impaired renal function

The drug Co-Perineva® is contraindicated in patients with severe renal failure (CK less than 30 ml/min) (see section “Contraindications”).

Patients with moderately severe renal impairment (CKR 30-60 ml/min) are recommended to start therapy with the required doses of drugs (in monotherapy) included in Co-Perineva®.

The maximum daily dose of Co-Perineva® is 1.25 mg + 4 mg.

Patients with CK³ 60 ml/min do not need dose adjustment. Creatinine and serum potassium concentrations should be monitored regularly during the therapy.

Patients with impaired liver function

The drug is contraindicated in patients with severe hepatic insufficiency (see “Contraindications”).

Dose adjustment is not required in moderately severe hepatic failure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, but special caution should be exercised when using Co-Perineva® in patients with ischemic heart disease and cerebrovascular insufficiency. In such patients, treatment should be started with a dose of Co-Perineva® 0.625 mg + 2 mg (starting dose).

Diabetes mellitus

In patients with type 1 diabetes mellitus (risk of spontaneous increase in plasma potassium content) treatment should be started with a low dose of the drug and under close medical supervision.

In the first month of therapy with ACE inhibitors, plasma glucose concentrations should be monitored closely in patients with diabetes treated with oral hypoglycemic agents or insulin.

Co-Perineva®

Lithium preparations

The concomitant use of Co-Perineva® with lithium drugs is not recommended (see “Interaction with other medicinal products”).

Kidney function impairment

Therapy with Co-Perineva® is contraindicated in patients with severe renal insufficiency (CKR less than 30 ml/min). Some patients with arterial hypertension without previous renal dysfunction may show laboratory signs of functional renal failure during Co-Perineva therapy. In this case, treatment with Co-Perineva® should be stopped. Subsequently, combination therapy may be resumed with low-dose Co-Perineva® or with perindopril and indapamide in monotherapy.

These patients require regular monitoring of serum potassium and creatinine 2 weeks after initiation of therapy and every 2 months thereafter with Co-Perineva®.

Renal failure develops more frequently in patients with severe CHF or underlying renal impairment, including renal artery stenosis.

Arterial hypotension and impaired water-electrolyte balance

In case of initial hyponatremia there is a risk of sudden BP decrease (especially in patients with renal artery stenosis). 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.

If BP is significantly decreased, intravenous injection of 0.9% sodium chloride solution may be necessary.

Transient arterial hypotension is not a contraindication for further therapy. After recovery of RBC and BP, therapy with Co-Perineva® may be resumed using low doses of the drug, or using perindopril and indapamide in monotherapy.

Potassium content

The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with DM or renal insufficiency. As in the case of combined use of other hypotensive agents and a diuretic, regular monitoring of plasma potassium is necessary.

Information on excipients

Please note that the excipients of Co-Perineva ® contains lactose monohydrate and therefore the drug is contraindicated in patients with lactose intolerance or lactase deficiency or glucose-galactose malabsorption syndrome (see contraindications section).

Children and adolescents

The use of Co-Perineva® in children and adolescents at

Synopsis

Tablets 0.625 mg + 2 mg:

Round, biconvex tablets, white or almost white, with beveled, one side engraved with a short line.

Tablets 1.25 mg + 4 mg:

Round, biconvex tablets white or nearly white, with a ridge on one side and a bevel.

Tablets 2.5 mg + 8 mg:

Round, biconvex tablets, white or nearly white, with a rib on one side.

Contraindications

– Lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Side effects

Perindopril has inhibitory effects on RAAS and reduces renal potassium ion excretion with indapamide. During the use of combination of indapamide + perindopril in dose of 2.5 mg + 8 mg the development of hypokalemia (potassium content in plasma less than 3.4 mmol/L) was observed in 6% of patients.

Overdose

Symptoms: expressed BP decrease, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to reduction of BOD), possible disorders of water-electrolyte balance (low sodium and potassium content in blood plasma).

treatment: gastric lavage and/or administration of activated charcoal, restoration of water-electrolyte balance in the hospital. With a significant decrease in BP, the patient should be transferred to the “lying” position on his back with his legs elevated, and then measures should be taken to increase the blood circulation (intravenous injection of 0.9% sodium chloride solution (intravenous (IV)). Perindoprilat, the active metabolite of perindopril, can be eliminated from the body by dialysis.

Pregnancy use

Pregnancy

Pregnancy

Similarities