Triplexam tablets coated film about 5 mg + 1.25 mg + 5 mg 30 pcs. (amlodipine, indapamide, Perindopril)

Release form

Film-coated tablets

Indications

As a therapy in patients with arterial hypertension with a decrease in blood pressure while taking amlodipine, indapamide and perindopril in the same doses.

Contraindications

Hypersensitivity to active and excipients that are part of the drug, sulfonamide derivatives, derivatives of dihydropyridine, other ACE inhibitors, any other substances that are part of the drug

Patients with severe hemodialysis renal failure (creatinine clearance (CC) less than 30 ml / min)

Moderate renal failure (creatinine clearance (CC) less than 60 ml / min) for ozirovki perindopril / indapamide 10 mg / 2.5 mg (i.e. Triplyxam® 5 mg + mg + 10 mg and Triplyxam® 10 mg + 2.5 mg + 10 mg)

Angioedema (Quincke's edema) with a history of ACE inhibitors (see Special Instructions)

Inherited / idiopathic angioedema

edema Pregnancy (see section "Use during pregnancy and during breastfeeding")

Period of breastfeeding (see section "Use during pregnancy and during breastfeeding")

Hepatic encephalopathy: Severe hepatic insufficiency hypotension (systolic blood pressure less than 90 mmHg)

shock (including cardiogenic)

Obstruction of the left ventricular outflow tract (e.g. clinically significant stenosis of the aortic orifice)

Hemodynamically unstable heart failure after acute

myocardial infarction Concomitant use with aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) <60 ml / min / 1.73 m2 of surface area body) (see sections "Interaction with other drugs" and "Pharmacodynamics")

Bilateral renal artery stenosis, stenosis of a single kidney artery

Concomitant use with prep arats that can cause polymorphic ventricular tachycardia of the pirouette type

Concurrent use with drugs that extend the QT interval

Concurrent use with potassium-sparing diuretics, potassium and lithium preparations, in patients with elevated plasma potassium

Age up to 18 years (efficacy and safety not established).

With caution (see also the sections “Special Instructions” and “Interaction with Other Medicines”)

The presence of only one functioning kidney, disturbances in water-electrolyte balance, systemic diseases of the connective tissue, therapy with immunosuppressants, allopurinol, procainamide (risk of neutropenia, agranulocytosis), acute myocardial infarction (and within 1 month after myocardial infarction), sinus node weakness syndrome (severe tachy and bradycardia), with simultaneous administration with inhibitors or induction ramie isoenzyme CYP3A4, hepatic failure mild to moderate severity, inhibition of bone marrow hematopoiesis, decreased blood volume (diuretics, diet with restriction of sodium chloride, vomiting, diarrhea, hemodialysis), hyperuricemia (especially accompanied by gout and urinary nephrolithiasis), the simultaneous use of dantrolene, estramustna, blood pressure lability, before the procedure of apheresis of low density lipoproteins (LDL) using the state after dextran sulfate kidney transplantation, patients of the Negroid race, coronary heart disease, cerebrovascular disease, renovascular hypertension, diabetes mellitus, chronic heart failure (III and IV functional class according to NYHA classification), the simultaneous use of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for edible salt and lithium, surgery / general anesthesia, hemodialysis using high-flow membranes (for example, AN69®), simultaneous desensitizing therapy with allergens (eg, hymenoptera poison), aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, advanced age.

Special instructions

All precautions associated with the use of individual components of the drug should be taken into account when using their fixed combination in the composition of the drug TriplexamВ®.

Amlodipine

Chronic heart failure

Patients with chronic heart failure should be treated with caution.

When using amlodipine in patients with chronic heart failure III and functional class according to NYHA classification, pulmonary edema may develop. Blockers of “slow” calcium channels, including amlodipine, should be used with caution in patients with chronic heart failure, due to the possible increased risk of adverse events from the cardiovascular system and mortality.

In patients with severe chronic heart failure (NYHA class IV functional class), treatment should begin with lower doses and under close medical supervision.

Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: an ACE inhibitor should be used in conjunction with beta-blockers.

Hypertensive crisis

The efficacy and safety of amlodipine in hypertensive crisis has not been established.

Indapamide

Hepatic encephalopathy

In the presence of impaired liver function, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking a diuretic.

Photosensitivity

Cases of a photosensitivity reaction have been reported with thiazide and thiazide-like diuretics (see section “Side effects”). If a photosensitivity reaction develops while taking the drug, treatment should be discontinued. If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Plasma calcium ion

Thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys and lead to a slight and temporary increase in plasma calcium levels. Severe hypercalcemia may result from previously undiagnosed hyperparathyroidism. In such cases, you should stop taking diuretics and conduct a study of the function of the parathyroid glands (see section "Side effects").

Uric acid

In patients with an increased concentration of uric acid in the blood plasma during therapy, the incidence of gout attacks may increase.

Perindopril

Potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes and

dietary supplements The simultaneous administration of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing salt substitutes and dietary supplements is not recommended (see section “Interaction with other medicinal products”).

Double blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence of an increased risk of hypotension, hyperkalemia and impaired renal function (including acute renal failure) while using ACE inhibitors with ARA II or aliskiren. Therefore, the double blockade of RAAS as a result of the combination of an ACE inhibitor with ARA II or aliskiren is not recommended (see sections "Interaction with other drugs" and "Pharmacodynamics"). If a double blockade is necessary, then this should be done under the strict supervision of a specialist with regular monitoring of renal function, plasma electrolytes and blood pressure. ACE inhibitors should not be used simultaneously with ARA II in patients with diabetic nephropathy.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

There are reports of the development of neutropenia / agranulocytosis, thrombocytopenia and anemia while taking ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. With extreme caution, perindopril should be used in patients with systemic diseases of the connective tissue, while taking immunosuppressants, allopurinol or procainamide, or when combined, especially in patients with impaired renal function.

Some of these patients had severe infections, in some cases, resistant to intensive antibiotic therapy. When prescribing perindopril, it is recommended that such patients periodically monitor white blood cells in the blood, and patients should inform the doctor of any signs of an infectious disease (for example, sore throat, fever) (see section “Side effects”).

Hypersensitivity / angioneurotic edema

When taking ACE inhibitors, including perindopril, in rare cases, angioedema of the face, limbs, lips, tongue, glottis and / or larynx may develop. This can occur at any time during therapy. When symptoms appear, the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually go away on their own, although antihistamines may be used to treat symptoms.

Angioneurotic edema, accompanied by laryngeal edema, can be fatal. Swelling of the tongue, glottis or larynx can lead to airway obstruction, in which case intensive care should be taken immediately. If such symptoms appear, an epinephrine (adrenaline) solution of 1: 1000 (0.3–0.5 ml) should be immediately administered and / or airway should be ensured. The patient should be under medical supervision until the symptoms disappear completely and persistently.

In patients of the Negroid race, a higher incidence of angioedema was observed with ACE inhibitors compared with other races.

In patients with a history of Quincke's edema, not associated with ACE inhibitors. the risk of its development when taking the drug may be increased (see section "Contraindications"). There are reports of rare cases of the development of angioedema of the intestine during therapy with ACE inhibitors. Moreover, patients had abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without prior angioedema of the face and with a normal level of C1 esterase. The diagnosis was made using computed tomography of the abdominal region, ultrasound or at the time of surgery. Symptoms disappeared after taking ACE inhibitors. Therefore, in patients with pain in the abdomen receiving ACE inhibitors, when conducting differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during desensitization

There are some reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients with a burdened allergic history or a tendency to allergic reactions undergoing desensitization procedures, and the use of an ACE inhibitor in patients receiving immunotherapy with hymenoptera venom should be avoided. However, an anaphylactoid reaction can be avoided by temporarily disabling the ACE inhibitor at least 24 hours before the start of the desensitization procedure.

Anaphylactoid reactions during LDL apheresis

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

Hemodialysis

Anaphylactoid reactions have been observed in patients receiving ACE inhibitors when hemodialysis using high-flow membranes (e.g. AN69В®). Therefore, it is desirable to use a different type of membrane or to use an antihypertensive agent of another pharmacotherapeutic group.

Pregnancy

ACE inhibitors are contraindicated during pregnancy. If continued therapy with ACE inhibitors is necessary, patients should switch to other types of antihypertensive therapy with an established safety profile when taken during pregnancy. When pregnancy occurs, ACE inhibitors should be discontinued immediately and, if necessary, alternative antihypertensive therapy should be started (see sections “Contraindications” and “Use in Pregnancy and During Breastfeeding”).

Cough

Dry cough may occur during therapy with an ACE inhibitor. The cough persists for a long time while taking drugs of this group and disappears after they are canceled. If a patient develops a dry cough, one should remember the possible iatrogenic nature of this symptom. If the doctor believes that the patient needs an ACE inhibitor therapy, you can consider continuing to take the drug.

Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

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

Ethnic differences

Perindopril, like other ACE inhibitors, apparently has a less pronounced antihypertensive effect in patients of the Negroid race compared to other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race often have low renin activity.

Surgery / General anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially when using general anesthesia, having antihypertensive effect.

It is recommended that you stop taking long-acting ACE inhibitors, including perindopril, as much as possible one day before surgery.

Patients with Renovascular Hypertension

Revascularization is a treatment for renovascular hypertension. Nevertheless, the use of ACE inhibitors has a beneficial effect in patients, both awaiting surgery, and when surgery is not possible.

When using the drug TriplexamВ® in patients with existing or with suspected renal artery stenosis, treatment should be started in a hospital with low doses with constant monitoring of the state of the kidneys and the level of potassium in the blood, since such patients may develop functional renal failure, which disappears when therapy is discontinued.

Atherosclerosis

The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with low doses of the drug.

Perindopril / Indapamide.

Lithium preparations

The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see section "Interaction with other drugs").

Arterial hypotension and impaired water-electrolyte balance

The presence of initial hyponatremia is associated with the risk of sudden development of arterial hypotension (especially in patients with renal artery stenosis). Therefore, when monitoring patients, attention should be paid to possible symptoms of dehydration and a decrease in the electrolyte content in blood plasma, for example, after diarrhea or vomiting. Such patients need regular monitoring of plasma electrolytes. With severe arterial hypotension, intravenous administration of a 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for continued therapy. After the restoration of BCC and blood pressure, you can resume therapy using low doses of the combination, or use the drug in monotherapy.

All diuretics can cause hyponatremia. which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, therefore, regular laboratory monitoring is necessary. More frequent monitoring of the content of sodium ions is indicated for elderly patients and patients with cirrhosis (see sections "Side effects" and "Overdose").

Patients with diabetes

In patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium ion content), treatment should begin with lower doses and under close medical supervision.

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin, during the first month of therapy, regular monitoring of plasma glucose concentration is necessary. It is necessary to control the level of glucose in the blood in patients with diabetes mellitus, especially in the presence of hypokalemia.

Amlodipine / perindopril

Hepatic insufficiency

In rare cases, while taking ACE inhibitors, cholestatic jaundice occurs. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If there is jaundice or a significant increase in the activity of “liver” enzymes in patients taking ACE inhibitors, you should stop taking the ACE inhibitor and consult a doctor (see the section "Side effects").

In patients with impaired liver function T and AUC of amlodipine increases. Amlodipine should be taken at the lowest doses and precautions should be taken, both at the beginning of treatment and when increasing the dose. In patients with severe hepatic insufficiency, the dose should be increased gradually, providing careful monitoring of the clinical condition.

TriplixamВ® has not been tested in patients with hepatic impairment. Given the effect of each component that is part of the drug, individually, TriplexamВ® is contraindicated in patients with severe hepatic impairment, and also requires special caution in the appointment of patients with moderate and mild hepatic impairment.

Amlodipine / indapamide / perindopril

Renal impairment

The drug is contraindicated in patients with severe renal failure (CC less than 30 ml / min) (see section "Contraindications").

In patients with moderate renal insufficiency (CC 30–60 ml / min), the use of Triplexam® is contraindicated in dosages containing 10 mg of perindopril and 2.5 mg of indapamide (i.e. dosage of Triplexam® 5 mg + 2.5 mg + 10 mg and 10 mg + 2.5 mg + 10 mg).

In some patients with arterial hypertension without a previous obvious impairment of renal function, laboratory signs of functional renal failure may appear during therapy. In this case, treatment with the drug should be discontinued with a further opportunity to resume combination therapy using low doses of the drug, or use the components of the drug in monotherapy. Such patients need regular monitoring of serum potassium and creatinine ions - 2 weeks after the start of therapy and every 2 months thereafter. Renal failure often occurs in patients with severe chronic heart failure or an initial impaired renal function, including renal artery stenosis.

TriplexamВ® is not recommended for patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.

There is a risk of arterial hypotension and / or renal failure (in the presence of chronic heart failure, dehydration and decreased electrolyte levels in blood plasma, etc.): in some pathological conditions, significant activation of RAAS can be noted, especially with severe hypovolemia and a decrease in blood plasma electrolytes (against the background of a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, renal artery stenosis (including bilateral), chronic heart failure or liver cirrhosis with edema and ascites.

Blockade of RAAS by ACE inhibitors may be accompanied by a sharp decrease in blood pressure and / or an increase in plasma creatinine concentration, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop sharply and the time of their onset can vary. In such cases, it is recommended to resume therapy starting from lower doses, gradually increasing them. In patients with coronary heart disease and cerebrovascular diseases, a sharp decrease in blood pressure can lead to myocardial infarction or impaired cerebral circulation.

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine in adult patients is below 25 mg / L or 220 Ојmol / L). In elderly patients, creatinine levels should be evaluated taking into account age, body weight and gender.

At the beginning of treatment with diuretics, patients due to hypovolemia and hyponatremia may experience a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in blood plasma. This transient functional renal failure is not dangerous for patients with unchanged renal function, however, in patients with initial renal failure, its severity may increase. Patients with renal failure may take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure.

Special studies on the use of the drug TriplexamВ® in renal failure have not been conducted. When using the drug TriplixamВ® for renal failure, the effects noted when taking the individual components of the drug should be taken into account.

Potassium ion in plasma

Combined therapy with indapamide, perindopril and amlodipine does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with other antihypertensive agents in combination with a diuretic, regular monitoring of the content of potassium ions in the blood plasma is necessary.

Hyperkalemia may develop in some patients during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, impaired renal function, advanced age (> 70 years), diabetes mellitus, some concomitant conditions (dehydration, acute decompensation of cardiac activity, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamteren, amiloride), potassium preparations or potassium-containing substitutes for edible salt, as well as the use of other agents that increase the content of potassium ions in blood plasma (for example, heparin). The use of food additives / potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for edible salt can lead to a significant increase in potassium in the blood, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If combined use of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of the content of potassium ions in the blood serum (see section "Interaction with other drugs"). Thiazide and thiazide-like diuretics are associated with a risk of hypokalemia. It is necessary to avoid hypokalemia (less than 3.4 mmol / l) in the following categories of high-risk patients: elderly patients and / or emaciated patients (even if they do not receive combined drug therapy), patients with cirrhosis with edema and ascites, patients with coronary heart disease, chronic heart failure. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of arrhythmias.

Patients with an extended QT interval also belong to the risk group, and it does not matter if this increase is caused by congenital causes or the effect of drugs.

Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, in particular polymorphic ventricular tachycardia of the pirouette type, which can be fatal. In all the cases described above, regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of the content of potassium ions must be carried out during the first week from the start of therapy.

If hypokalemia is detected, appropriate treatment should be prescribed.

Elderly patients

Before taking the drug, it is necessary to evaluate the functional activity of the kidneys and the content of potassium ions in blood plasma. At the beginning of therapy, the dose of the drug is selected, taking into account the degree of decrease in blood pressure, especially in the case of a decrease in the volume of circulating blood (BCC) and loss of electrolytes. Such measures can avoid a sharp decrease in blood pressure.

In elderly patients, an increase in dose should be carried out with caution (see sections "Dosage and Administration" and "Pharmacokinetics").

Influence on the ability to drive vehicles,

mechanisms Due to the possibility of weakness, dizziness with the use of TriplixamВ®, care must be taken when driving vehicles and working with other technical devices, requiring increased concentration of attention and speed of psychomotor reactions.

Composition

1 tablet 5 mg + 1.25 mg + 5 mg: contains active ingredients amlodipine besylate 6.935 mg, corresponds to 5.0 mg amlodipine, 1.25 mg indapamide and perindopril arginine 5 mg.

Dosage and administration

Inside, 1 tablet 1 time per day, preferably in the morning before meals.

The dose of TriplexamВ® is selected after a previous titration of doses of individual components. The maximum daily dose is 1 tablet at a dosage of 10.0 mg + 2.5 mg + 10.0 mg.

Special patient groups

Patients with renal failure (see Pharmacokinetics, Contraindications and Special Instructions)

TriplexamВ® is contraindicated in patients with severe renal failure (CC less than 30 ml / min) (see Contraindications ) For patients with moderate renal failure (CC 30-60 ml / min), TriplexamВ® is contraindicated in a dosage of 5.0 mg + 2.5 mg + 10.0 mg and 10.0 mg + 2.5 mg + 10.0 mg. It is recommended to start therapy with the selection of doses of monocomponents.

Ongoing medical supervision should include regular monitoring of plasma creatinine and potassium concentrations. Simultaneous use with aliskiren is contraindicated in patients with impaired renal function (GFR <60 ml / min / 1.73 m2 of body surface area) (see section "Contraindications").

Patients with hepatic impairment (see Pharmacokinetics Contraindications and Special Instructions)

Patients with severe hepatic insufficiency TriplexamВ® is contraindicated.

For patients with mild or moderate hepatic insufficiency, dose selection should be carried out with caution, since there are no unequivocal recommendations on the dosage of amlodipine for this group of patients.

Elderly patients (see section "Special instructions")

Excretion of perindoprilat in elderly patients is slowed down (See section "Pharmacokinetics"). Therapy should be carried out taking into account the function of the kidneys.

Pediatric Patients

There is currently no data on the safety and efficacy of TriplexamВ® in children and adolescents.

Side effects

The most common adverse reactions reported with perindopril, indapamide and amlodipine as monotherapy were: dizziness, headache, paresthesia, vertigo, drowsiness, visual impairment, tinnitus, palpitations, flushing facial skin, decreased blood pressure (and hypotension-related effects), cough, shortness of breath, gastrointestinal upsets (abdominal pain, constipation, diarrhea, taste perversion, nausea, dyspepsia, vomiting), pruritus, rash, maculopapular rash, muscle spasm s, swelling in the ankles, asthenia, swelling and fatigue.

Overdose

There is no information on an overdose of Triplexam®.

Amlodipine

Information on overdose of amlodipine is limited.

Symptoms.

There is evidence of the development of excessive peripheral vasodilation with the possible development of reflex tachycardia. The risk of developing severe and persistent arterial hypotension, including with the development of shock and death.

Methods of providing medical care.

With clinically significant hypotension resulting from an overdose of amlodipine, it is necessary to carry out activities aimed at maintaining the function of the cardiovascular system, including placing the limbs in an elevated position, controlling bcc and urine output, monitoring of cardiac and respiratory activity.

To normalize vascular tone and blood pressure, vasoconstrictor drugs can be used, provided that there are no contraindications to their use. To eliminate the effects of calcium channel blockade, intravenous administration of calcium gluconate is possible.

In some cases, gastric lavage may be effective. In healthy volunteers, it has been demonstrated that the use of activated carbon within 2 hours after taking 10 mg of amlodipine reduces the rate of absorption of amlodipine.

Since amlodipine binds to proteins, hemodialysis is ineffective.

Combination of perindopril / indapamide

Symptoms

For the combination of perindopril / indapamide, the most likely symptom of an overdose is arterial hypotension, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion, and oligouria, which can go into anuria (as a result of hypovolemia). Electrolyte disturbances (hyponatremia, hypokalemia) may also occur.

Methods of providing medical care

Emergency measures are reduced to removing the drug from the body: washing the stomach and / or taking activated charcoal with the subsequent restoration of water-electrolyte balance.

With a significant decrease in blood pressure, the patient should be placed in the supine position with raised legs, and if necessary, correct hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Perindoprilat, the active metabolite of perindopril, can be removed from the body by dialysis (see Pharmacokinetics section)

Storage conditions

At a temperature not exceeding 25 ° C. Keep out of the reach of children.

Expiration

2 years.

Deystvuyuschee substances

amlodipine, indapamide, Perindopril



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