Triplixam tabs 5mg + 1.25mg + 5mg #30

Triplixam instruction

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Triplixam is a combined drug with an antihypertensive effect.

Release form and composition

The dosage form of Triplixam is film-coated tablets: white, oblong biconvex, on one side engraved with the numbers from 1 to 5 (depending on the dosage), on the other - the company logo (in a cardboard box 1 bottle of 29 or 30 tablets; for hospitals - 3 vials of 30 tablets and instructions for the use of Triplixam).
Active substances: amlodipine (in the form of amlodipine besylate), indapamide, perindopril arginine. Dose of active substances in 1 tablet (the numbering corresponds to the engraving on the tablet):
    5 mg + 0.625 mg + 2.5 mg.
    5 mg + 1.25 mg + 5 mg.
    10 mg + 1.25 mg + 5 mg.
    5 mg + 2.5 mg + 10 mg.
    10 mg + 2.5 mg + 10 mg.
Auxiliary components:
    core: colloidal silicon dioxide, magnesium stearate, calcium carbonate + pregelatinized corn starch, pregelatinized starch, microcrystalline cellulose, croscarmellose sodium;
    film shell: titanium dioxide, hypromellose, macrogol-6000, glycerol, magnesium stearate.

Pharmacological properties

Triplixam is a combination drug that includes three antihypertensive agents:
    Amlodipine: a dihydropyridine derivative, belongs to the BMCC (slow calcium channel blockers).
    Indapamide: is a sulfonamide diuretic.
    Arginine perindopril: an ACE (angiotensin converting enzyme) inhibitor that converts angiotensin I to angiotensin II.
The components mutually complement the action aimed at controlling blood pressure (blood pressure) in patients with hypertension (arterial hypertension).
The pharmacological properties of Triplixam combine the individual effects of its active substances. In addition, due to synergy in such a combination, the hypotensive effect of each of the substances is enhanced.
Mechanism of action:
    amlodipine provides inhibition of the transmembrane transition of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall;
    indapamide is a sulfonamide derivative with an indole ring, its pharmacological properties are similar to thiazide diuretics, which inhibit the reabsorption of sodium ions in the cortical segment of the nephron loop. At the same time, there is an increase in the excretion of chlorine and sodium ions by the kidneys and, to a lesser extent, magnesium and potassium ions. This process proceeds with an antihypertensive effect and an increase in urine output;
    perindopril is an ACE inhibitor. ACE, or kininase II, is an exopeptidase that converts angiotensin I to angiotensin II (a vasoconstrictor). The enzyme also stimulates the production of aldosterone by the adrenal cortex and the destruction of bradykinin, which has a vasodilating property, to an inactive heptapeptide.
Thanks to the use of perindopril, the development of the following effects is noted:
    decreased secretion of aldosterone;
    an increase in the plasma activity of renin in the blood (negative feedback mechanism);
    decrease in OPSS (total peripheral vascular resistance) in case of prolonged use; this is mainly due to the effect on the vessels in the kidneys and muscles. These effects are not accompanied by retention of fluid or sodium ions or the appearance of reflex tachycardia with prolonged therapy.
The antihypertensive properties of the substance are manifested in patients with low / normal plasma renin activity in the blood.
The therapeutic effect of perindopril is due to perindoprilat, an active metabolite. Other metabolites have no pharmacological activity.
Perindopril contributes to the normalization of the heart, which is associated with a decrease in preload and afterload. This is due to a decrease in OPSS and a vasodilating effect on the veins, which is probably associated with the activation of the prostaglandin system.
During the study of hemodynamic parameters in patients with CHF (chronic heart failure), the following effects were established:
    decrease in systemic vascular resistance and filling pressure in the right and left ventricles of the heart;
    increased cardiac index and cardiac output;
    increased muscle peripheral circulation.
There is also an increase in exercise tolerance.

Amlodipine

The antihypertensive efficacy of amlodipine is based on a direct effect on the smooth muscle cells of the vascular walls. The mechanism of antianginal activity is not fully known, however, it has been established that amlodipine reduces the total ischemic load as follows:
    promotes the expansion of peripheral arterioles, due to a decrease in OPSS (afterload). This leads to a decrease in energy consumption and myocardial oxygen demand;
    promotes the expansion of the coronary arteries and arterioles in the ischemic and intact area. At the same time, during spasm of the coronary arteries (in patients with Prinzmetal's angina), an improvement in coronary blood flow and myocardial oxygen supply is noted.
The use of amlodipine once a day in patients with hypertension for 24 hours maintains a clinically significant decrease in blood pressure in the standing and lying position. The development of antihypertensive action occurs slowly, which avoids the occurrence of acute arterial hypotension.
Amlodipine does not have undesirable metabolic effects, does not affect lipid metabolism, and does not lead to changes in lipid-lowering blood plasma parameters. It can be used in patients with concomitant bronchial asthma, gout and diabetes mellitus.

Indapamide

In the case of using indapamide as monotherapy, the antihypertensive effect is provided for 24 hours. It manifests itself with therapy at doses that have minimal diuretic effects.
The hypotensive activity of the substance is based on improving the elastic properties of large arteries, reducing the total peripheral and arteriolar vascular resistance.
The use of indapamide can reduce left ventricular hypertrophy.
Thiazide / thiazide-like diuretics, used in certain doses, reach a therapeutic plateau. However, the incidence of side effects continues to increase with a further increase in the dose of the drug. Therefore, if the therapeutic effect is not achieved by taking the recommended dose, its further increase is not recommended.
When conducting studies of various durations (from short to long-term), in which patients with hypertension took part, it was shown that indapamide on indicators of lipid metabolism, including on the level of cholesterol, triglycerides, LDL and HDL (low and high density lipoproteins ) does not affect. Also, the substance does not affect the indicators of carbohydrate metabolism, including in patients with diabetes mellitus.

Perindopril

The substance is effective in the treatment of hypertension of any severity. Its use can reduce systolic and diastolic blood pressure in the standing and lying positions.
The development of the maximum hypotensive effect is observed 4-6 hours after a single oral dose, its duration is 24 hours.
24 hours after oral administration, there is a pronounced (about 80%) residual inhibition of ACE.
If there is a positive response to treatment, blood pressure normalizes within a month, this result is further maintained without the development of tachycardia.
Cancellation of perindopril is not accompanied by the development of the rebound effect.
The substance has a vasodilating effect, reduces left ventricular hypertrophy, and also its effect is aimed at restoring the elasticity of large arteries and structures of the vascular wall of small arteries.
With the combined use of thiazide diuretics, the severity of the antihypertensive effect increases. In addition, the combination of an ACE inhibitor with a thiazide diuretic reduces the risk of hypokalemia associated with diuretic therapy.
In patients with hypertension, regardless of age, the combination of perindopril and indapamide has a dose-dependent hypotensive effect on diastolic and systolic blood pressure in the supine and standing positions. In the course of clinical studies, a more pronounced antihypertensive effect was found against the background of combined therapy of these substances compared with monotherapy.

Pharmacokinetics

With the combined use of perindopril, indapamide and amlodipine, their pharmacokinetic characteristics do not change in comparison with the separate administration of these substances.

Amlodipine

After oral administration, the substance is well absorbed in the gastrointestinal tract. Cmax (maximum concentration) in blood plasma is reached 6–12 hours after administration.
The absolute bioavailability of amlodipine is approximately 64-80%. Vd (volume of distribution) - about 21 l / kg. Communication with blood plasma proteins at the level of ~ 97.5%. When taken simultaneously with food, the bioavailability value does not change.
Metabolism of amlodipine occurs in the liver, resulting in the formation of metabolites that do not have activity. Excreted by the kidneys: unchanged - 10% of the dose taken, in the form of metabolites - 60%.
The final T1 / 2 (half-life) of amlodipine from blood plasma is from 35 to 50 hours, this makes it possible to take the drug once a day.
In elderly patients, a slowdown in the clearance of amlodipine is observed, as a result, the value of AUC (area under the concentration-time curve) and T1 / 2 increases. In patients with CHF, the increase in AUC and T1 / 2 corresponds to the expected value for this age group.
Information on the use of amlodipine in patients with hepatic impairment is limited. In patients belonging to this group, there is a decrease in the clearance of amlodipine, resulting in an increase in T1 / 2 and AUC by about 40-60%.

Indapamide

Indapamide is completely and rapidly absorbed in the gastrointestinal tract. Cmax of a substance in blood plasma is reached 1 hour after ingestion.
Binds to blood plasma proteins at a level of 79%.
Т1 / 2 - from 14 to 24 hours (on average - 18 hours). With repeated admission, cumulation is not noted. Indapamide is excreted as inactive metabolites, mainly by the kidneys and through the intestines (70 and 22%, respectively).

Perindopril

After oral administration, the substance is rapidly absorbed in the gastrointestinal tract, Cmax in blood plasma is reached in 1 hour. The active metabolite of perindopril is perindoprilat.
T1 / 2 from blood plasma - 1 hour. Food intake slows down the conversion of perindopril to perindoprilat, which affects its bioavailability. In this regard, the drug should be taken in the morning, before meals, 1 time per day.
Vd of free perindoprilat is about 0.2 l / kg. It binds to blood plasma proteins, mainly ACE, at a level of ~ 20% (the indicator is dose-dependent).
Perindopril has no pharmacological activity. Approximately 27% of the total amount of ingested substance enters the bloodstream as perindoprilat. In addition to it, 5 more metabolites are formed, which do not possess pharmacological activity. Cmax of perindoprilat in blood plasma is achieved 3-4 hours after administration.
It is excreted from the body by the kidneys. The final T1 / 2 of the free fraction is approximately 17 hours, the equilibrium state is reached in 4 days.
The plasma concentration of perindopril is dose-dependent.
The excretion of perindoprilat is slowed down in old age, as well as in patients with heart and renal failure.
When choosing a dose, it is important to take into account the severity of renal failure.
The dialysis clearance of perindoprilat is 70 ml / min.
Pharmacokinetic parameters of perindopril in patients with liver cirrhosis are impaired: hepatic clearance is reduced by 2 times. In this case, the amount of perindoprilat formed does not change, therefore, dose adjustment is not required.

Indications for use

Triplixam is prescribed for the treatment of hypertension with a decrease in blood pressure while taking the same doses of amlodipine, indapamide and perindopril.

Contraindications

Absolute:
    patients on hemodialysis;
    severe renal failure (creatinine clearance less than 30 ml / min);
    moderate renal impairment (creatinine clearance less than 60 ml / min) for the dosage of a combination of 10 mg perindopril + 2.5 mg indapamide (i.e. for Triplixam 5 mg + 2.5 mg + 10 mg and 10 mg + 2.5 mg + 10 mg);
    untreated heart failure in the stage of decompensation;
    the presence of a burdened history of angioedema (angioedema) while taking ACE inhibitors;
    angioedema (hereditary or idiopathic);
    severe liver failure;
    hepatic encephalopathy;
    hypokalemia;
    shock (including cardiogenic);
    severe arterial hypotension (with systolic blood pressure less than 90 mm Hg);
    hemodynamically unstable heart failure after acute myocardial infarction;
    obstruction of the outflow tract of the left ventricle (in particular, clinically significant stenosis of the orifice of the aorta);
    stenosis of an artery of a single kidney, bilateral stenosis of the renal arteries;
    combination therapy with drugs that can cause polymorphic ventricular tachycardia such as pirouette;
    combined therapy with aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (at a glomerular filtration rate <60 ml / min / 1.73 m2);
    combination therapy with drugs that prolong the QT interval;
    combination therapy with lithium and potassium preparations, potassium-sparing diuretics, in patients with increased plasma potassium levels in the blood;
    pregnancy and lactation;
    age under 18;
    individual intolerance to the components of the drug, as well as derivatives of sulfonamide and dihydropyridine, other ACE inhibitors.
Relative (Triplixam is prescribed under medical supervision):
    systemic connective tissue diseases;
    violations of water and electrolyte balance;
    having only one functioning kidney;
    cerebrovascular diseases;
    Ischemic heart disease (ischemic heart disease);
    acute myocardial infarction (and within one month after damage to the heart muscle);
    chronic heart failure (NYHA classification - III and IV functional class);
    sick sinus syndrome (severe brady and tachycardia);
    aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy;
    renovascular hypertension;
    diabetes;
    hyperuricemia (especially with urate nephrolithiasis and gout);
    oppression of bone marrow hematopoiesis;
    liver failure, which is mild to moderate;
    lability of blood pressure;
    reduced volume of circulating blood (associated with taking diuretics, adherence to a diet with limited salt, diarrhea, vomiting, hemodialysis);
    combined therapy with dantrolene, estramustine;
    combined therapy with allopurinol, immunosuppressants, procainamide;
    combination therapy with inducers or inhibitors of the CYP3A4 isoenzyme;
    combined therapy with potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for table salt and lithium;
    condition before the procedure of LDL apheresis with dextran sulfate;
    condition after kidney transplantation;
    hemodialysis using high-flow membranes;
    surgical intervention and the use of general anesthesia;
    desensitizing treatment with allergens (for example, hymenoptera venom);
    belonging to the Negroid race;
    elderly age.

Triplixam, instructions for use: method and dosage

Triplixam is taken orally 1 time per day, 1 tablet, preferably in the morning before meals.
The dosage regimen is selected after previously titrated doses of active substances. The maximum dose is 1 tablet of 10 mg + 2.5 mg + 10 mg per day.

Side effects

The use of perindopril, indapamide and amlodipine as monotherapy most often caused the following adverse reactions: flushing of the face, headache, dizziness, paresthesia, drowsiness, vertigo, tinnitus, visual impairment, palpitations, lowering blood pressure (including effects associated with hypotension ), shortness of breath, cough, gastrointestinal disorders (in the form of abdominal pain, constipation, diarrhea, taste perversion, nausea, dyspepsia, vomiting), skin rashes, maculopapular rash, pruritus, swelling in the ankle area, muscle cramps, asthenia, fatigue, swelling.
Estimation of the incidence of adverse reactions:> 10% - very often; > 1% and <10% - often; > 0.1% and <1% - infrequently; > 0.01% and <0.1% - rarely; <0.01%, including individual messages - very rare; with an unspecified frequency - in cases where it is impossible to establish the frequency of development of a violation according to the available data.
Amlodipine:
    lymphatic system and blood: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia;
    nervous system: often - dizziness, headache, drowsiness; infrequently - paresthesia, fainting, tremor, hypesthesia, dysgeusia (taste perversion); very rarely - parosmia (perversion of smell), hypertonicity, peripheral neuropathy, amnesia, migraine, apathy, ataxia, agitation; with an unknown frequency - extrapyramidal disorders;
    immune system: very rarely - hypersensitivity reactions;
    cardiovascular system: often - flushes of blood to the skin of the face, palpitations; infrequently - arterial hypotension and associated symptoms; very rarely - heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction (possibly associated with an excessive decrease in blood pressure in high-risk patients), the onset / worsening of CHF, vasculitis, orthostatic hypotension;
    liver and biliary tract: very rarely - hepatitis, cholestatic jaundice;
    digestive system: often - nausea, abdominal pain; infrequently - constipation, flatulence, changes in the rhythm of bowel movements, dyspepsia, dryness of the oral mucosa, vomiting, diarrhea; very rarely - pancreatitis, gingival hyperplasia, gastritis;
    musculoskeletal system: infrequently - muscle spasms, myalgia, back pain, arthralgia, arthrosis; rarely - myasthenia gravis;
    skin and subcutaneous tissues: infrequently - increased sweating, rash, itching / rash, discoloration of the skin, alopecia, purpura; rarely - dermatitis; very rarely - urticaria, angioedema, Quincke's edema, photosensitivity reaction, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, cold sweat, xeroderma;
    metabolism: very rarely - hyperglycemia: infrequently - anorexia; rarely - increased appetite;
    infectious and invasive lesions: infrequently - rhinitis;
    psyche: infrequently - insomnia, mood lability (including anxiety), depression, unusual dreams, increased excitability; rarely - confusion of consciousness;
    organ of hearing: infrequently - ringing in the ears;
    organ of vision: infrequently - visual impairment (including diplopia), impaired accommodation, conjunctivitis, eye pain, xerophthalmia;
    respiratory system: infrequently - shortness of breath, epistaxis; very rarely - cough;
    genitals and mammary gland: infrequently - erectile dysfunction, gynecomastia;
    kidneys and urinary tract: infrequently - violation of urination, nocturia, pollakiuria (frequent urination), painful urination;
    laboratory / instrumental indicators: infrequently - weight change; very rarely - increased activity of hepatic transaminases, hyperbilirubinemia;
    general disorders: often - increased fatigue, peripheral edema (feet and ankles), edema; infrequently - chest pain, asthenia, pain, malaise, chills, thirst.
Indapamide:
    immune system: infrequently - hypersensitivity reactions;
    nervous system: rarely - headache, vertigo, paresthesia; with an unspecified frequency - fainting;
    digestive system: infrequently - vomiting; rarely - constipation, nausea, dry mouth; very rarely - pancreatitis;
    cardiovascular system: very rarely - arterial hypotension and associated symptoms, cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation); with an unknown frequency - polymorphic ventricular tachycardia of the pirouette type (there is a possibility of death);
    lymphatic system and blood: very rarely - agranulocytosis, leukopenia, aplastic anemia, thrombocytopenia, hemolytic anemia;
    metabolism: very rarely - hypercalcemia; with an unknown frequency - hyponatremia, a decrease in potassium content and the development of hypokalemia, especially significant for patients at risk;
    organ of vision: with an unknown frequency - visual impairment (including diplopia), myopia, blurred vision;
    liver and biliary tract: very rarely - impaired hepatic function; with an unknown frequency - hepatitis, the development of hepatic encephalopathy in the case of liver failure;
    kidneys and urinary tract: very rarely - renal failure;
    skin and subcutaneous tissue: often - maculopapular rash; infrequently, purple; very rarely - urticaria, angioedema, Quincke's edema, Stevens-Johnson syndrome, toxic epidermal necrolysis; with an unknown frequency - a photosensitivity reaction, exacerbation of an existing systemic lupus erythematosus;
    laboratory / instrumental parameters: with an unknown frequency - an increase in the activity of hepatic transaminases, an increase in the concentration of uric acid in the blood, an extension of the QT interval on an electrocardiogram (ECG);
    general disorders: rarely - increased fatigue.
Perindopril:
    nervous system: often - vertigo, dysgeusia, dizziness, paresthesia, headache; infrequently - drowsiness, fainting; very rarely - stroke (possibly associated with an excessive decrease in blood pressure in high-risk patients);
    lymphatic system and blood: infrequently - eosinophilia; very rarely - agranulocytosis, hemolytic anemia, thrombocytopenia, pancytopenia, leukopenia, neutropenia;
    digestive system: often - vomiting, abdominal pain, nausea, indigestion, constipation, diarrhea; infrequently - xerostomia; very rarely - pancreatitis, angioedema of the intestine;
    cardiovascular system: often - arterial hypotension and related symptoms; infrequently - palpitations, vasculitis, tachycardia; very rarely - angina pectoris, cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction (possibly associated with an excessive decrease in blood pressure in high-risk patients);
    respiratory system: often - cough, shortness of breath; infrequently - bronchospasm; very rarely - eosinophilic pneumonia;
    infectious and invasive lesions: very rarely - rhinitis;
    organ of hearing: often - ringing in the ears;
    organ of vision: often - visual impairment (including diplopia);
    metabolism: infrequently - hypoglycemia, hyperkalemia (reversible), hyponatremia;
    psyche: infrequently - mood lability (including anxiety), sleep disturbance, very rarely - confusion;
    liver and biliary tract: very rarely - hepatitis, cholestatic jaundice
    kidneys and urinary tract: infrequently - renal failure; very rarely - acute renal failure;
    musculoskeletal system: often - muscle spasm; infrequently - arthralgia, myalgia;
    skin and subcutaneous tissue: often - itchy skin / rash; infrequently - urticaria, angioedema, Quincke's edema, increased sweating, photosensitivity reaction, pemphigoid; very rarely - erythema multiforme;
    genitals and mammary gland: infrequently - erectile dysfunction;
    injuries, complications after interventions, poisoning: infrequently - falls;
    laboratory / instrumental parameters: infrequently - an increase in the concentration of urea and creatinine in the blood; rarely - increased activity of hepatic transaminases, hyperbilirubinemia; very rarely - a decrease in hematocrit and hemoglobin;
    general disorders: often - asthenia; infrequently - peripheral edema (feet and ankles), malaise, fever.

Overdose

There is no information about an overdose of Triplixam.

Amlodipine

Information on the symptoms of overdose is limited.
There is information about the development of excessive peripheral vasodilation with the likely occurrence of reflex tachycardia, as well as the risk of persistent and severe arterial hypotension, possibly with the development of shock and death.
With clinically significant hypotension, measures are taken to maintain the function of the cardiovascular system, including transferring the patient to a horizontal position (on the back) with raised legs, monitoring urine output and circulating blood volume, respiratory and cardiac activity.
To normalize blood pressure and vascular tone, vasoconstrictors can be used, provided that there are no contraindications to their use.
In order to eliminate the consequences of calcium channel blockade, calcium gluconate can be administered intravenously. In some cases, gastric lavage is effective. It was found that the use of activated carbon within 2 hours after taking amlodipine provides a decrease in the rate of absorption of the substance.
Amlodipine binds to proteins, so hemodialysis is ineffective.

Perindopril + indapamide

The most likely symptoms of an overdose: arterial hypotension (possibly in combination with vomiting, nausea, convulsions, drowsiness, confusion, dizziness, oliguria, which can turn into anuria, which is associated with hypovolemia), electrolyte disturbances (in the form of hypokalemia, hyponatremia).
Treatment is aimed at removing perindopril + indapamide from the body. For this, gastric lavage and / or intake of activated charcoal is indicated. In the future, measures are prescribed to restore the water-electrolyte balance. With a pronounced decrease in blood pressure, the patient is transferred to a horizontal position (on the back) with raised legs.
According to indications, hypovolemia is corrected (for example, intravenous infusion of 0.9% sodium chloride solution is prescribed). Perindoprilat, which is the active metabolite of perindopril, can be removed from the body through dialysis.

Special instructions

During the use of Triplixam, it is necessary to take into account all the precautions that are associated with the intake of individual components of the drug.

Amlodipine

With CHF, therapy should be carried out with caution, which is associated with an increased risk of cardiovascular disorders and mortality.
Patients with coronary artery disease and hypertension should not stop taking β-blockers while taking Triplixam.
In hypertensive crisis, the safety profile of amlodipine has not been studied.

Indapamide

In patients with impaired hepatic function, diuretic treatment can cause the development of hepatic encephalopathy. In this case, immediate withdrawal of indapamide is required.
With the development of a photosensitivity reaction, immediate withdrawal of the diuretic is required. In cases where such cancellation is impossible, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.
The use of diuretics can help to reduce the excretion of calcium ions by the kidneys, and lead to a temporary and insignificant increase in the plasma content of calcium ions in the blood. Previously undiagnosed hyperparathyroidism can lead to the development of severe hypercalcemia. In such cases, it is required to cancel indapamide and conduct a study of the function of the parathyroid glands.
During therapy, patients with an increased plasma concentration of uric acid in the blood may experience an increase in the frequency of gout attacks.

Perindopril

The simultaneous use of perindopril with potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for table salt and food additives is not recommended.
There is evidence of an increased risk of arterial hypotension, impaired renal function and hyperkalemia with the combined use of ACE inhibitors with ARA II or aliskiren. In patients with diabetic nephropathy, ACE inhibitors should not be used concomitantly with ARA II.
The use of perindopril requires special care in patients with systemic connective tissue diseases, during therapy with immunosuppressants, procainamide or allopurinol, or their combination, especially in the presence of impaired renal function. This is associated with a high likelihood of developing neutropenia / agranulocytosis, anemia, and thrombocytopenia. There is also information about the development of severe infections in this group of patients, sometimes showing resistance to intensive antibiotic therapy.
If symptoms of hypersensitivity / angioedema appear, perindopril should be withdrawn immediately.
A higher incidence of angioedema is observed in patients of the Negroid race. With a history of Quincke's edema, not associated with taking ACE inhibitors, the risk of developing this disorder while taking the drug is increased.
A dry cough may occur while taking perindopril.
The use of perindopril in patients undergoing surgery with the use of general anesthesia can cause a pronounced decrease in blood pressure, especially in cases of using drugs for general anesthesia with an antihypertensive effect. The day before the operation, perindopril is recommended to be canceled.
In patients with cerebral circulation insufficiency and ischemic heart disease, treatment should be started with low doses of the drug, which is associated with an increased risk of arterial hypotension.

Perindopril + indapamide

In the presence of initial hyponatremia, the risk of sudden development of arterial hypotension increases (especially in patients with renal artery stenosis). Observing patients, you need to pay attention to possible symptoms of dehydration and a decrease in the plasma electrolyte content in the blood. A pronounced decrease in blood pressure may require intravenous administration of 0.9% sodium chloride solution.
Patients with type 1 diabetes mellitus should start therapy with lower doses, carefully monitoring the patient's condition.

Amlodipine + perindopril

In the event of jaundice or a significant increase in the activity of liver enzymes, it is necessary to cancel therapy and consult a doctor.
In the presence of impaired hepatic function, T1 / 2 and AUC of amlodipine increases. Amlodipine should be started at the lowest dose, with precautions taken.

Amlodipine + indapamide + perindopril (Triplixam)

If laboratory signs of functional renal failure appear, if this was not preceded by obvious renal dysfunction, the drug should be discontinued. In the future, the combination therapy can be resumed using low doses of the drug. It is also possible to use the components of Triplixam in monotherapy mode.
Thiazide / thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function. In older patients, creatinine levels should be assessed based on age, sex, and weight.
For renal impairment, patients can take standard doses of amlodipine. Changes in the plasma concentration of a substance do not correlate with the degree of renal failure.
The combined use of indapamide, perindopril and amlodipine does not prevent the development of hypokalemia, especially in patients with renal failure or diabetes mellitus.
If hypokalemia is detected, appropriate therapy should be prescribed.

Influence on the ability to drive vehicles and complex mechanisms

Patients during therapy when driving vehicles should be careful, which is associated with the likelihood of dizziness and weakness.

Application during pregnancy and lactation

Triplixam is not prescribed during pregnancy / lactation.
In cases of pregnancy planning or when it occurs, Triplixam is immediately canceled and an alternative antihypertensive treatment with a proven safety profile is prescribed.

Childhood use

The drug is not prescribed to patients under 18 years of age, which is due to the lack of data confirming or refuting the efficacy and safety of therapy in this group of patients.

With impaired renal function

Contraindications:
    patients on hemodialysis;
    severe renal failure (creatinine clearance less than 30 ml / min);
    moderate renal failure (creatinine clearance less than 60 ml / min) for the dosage of a combination of 10 mg perindopril + 2.5 mg indapamide (i.e., for Triplixam 5 mg + 2.5 mg + 10 mg and 10 mg + 2.5 mg + 10 mg);
    stenosis of an artery of a single kidney, bilateral stenosis of the renal arteries.
If there is only one functioning kidney, Triplixam is prescribed under medical supervision.

For violations of liver function

    severe hepatic impairment, hepatic encephalopathy: therapy is contraindicated;
    mild to moderate hepatic impairment: Triplixam is prescribed under medical supervision. The selection of the dose should be carried out with caution, since there are no unequivocal recommendations for the dosage of amlodipine for this group of patients.

Use in the elderly

When prescribing Triplixam to elderly patients, it is necessary to take into account the functional state of the kidneys.

Drug interactions

As a result of clinical studies, it was found that double blockade of the renin-angiotensin-aldosterone system (RAAS) associated with the simultaneous administration of ACE inhibitors, ARA II or aliskiren causes an increase in the incidence of disorders such as hyperkalemia, arterial hypotension and renal dysfunction (including including acute renal failure), in comparison with situations when therapy is carried out with the use of only one drug that affects the RAAS.
Certain drugs may increase the risk of developing hyperkalemia. This applies to aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs, heparin, immunosuppressants (including tacrolimus or cyclosporine), trimethoprim. With the combined therapy of Triplixam with these agents, the risk of developing hyperkalemia increases.

Contraindicated combinations

With the combined use of Triplixam with aliskiren in patients with renal insufficiency (glomerular filtration rate <60 ml / min / 1.73 m2) or diabetes mellitus, the likelihood of deterioration in renal function, the development of hyperkalemia, an increase in the incidence of cardiovascular disorders and mortality from cardiovascular disease.

Deprecated combinations

Amlodipine:
    verapamil, dantrolene (intravenous administration): the development of ventricular fibrillation with a lethal outcome and collapse in combination with hyperkalemia; in patients who are susceptible to malignant hyperthermia, as well as during therapy for malignant hyperthermia, the combination should be avoided;
    grapefruit or grapefruit juice: the bioavailability of amlodipine may increase, which in turn can cause increased blood pressure lowering effects.
Perindopril:
    aliskiren (in patients without diabetes mellitus or impaired renal function): an increased risk of hyperkalemia, impaired renal function and an increased incidence of cardiovascular impairment and mortality;
    ARA II inhibitors: the likelihood of developing hyperkalemia, hypotension, fainting and deterioration of renal function (including acute renal failure) increases against the background of established atherosclerotic diseases, chronic heart failure or diabetes mellitus with target organ damage; double blockade of the RAAS (in particular, when an ACE inhibitor is combined with ARA II) can be carried out only in some cases under careful monitoring of potassium content, renal function and blood pressure;
    estramustine: the risk of side effects, including angioedema, increases;
    potassium-sparing diuretics (amiloride, triamterene), potassium salts: the development of hyperkalemia (with a possible fatal outcome), especially against the background of impaired renal function (additional effects associated with hyperkalemia); if necessary, the combined use of therapy should be carried out with caution under regular monitoring of serum potassium in the blood.
The combined use of perindopril + indapamide with lithium preparations is not recommended. If such therapy is necessary, regular monitoring of the plasma lithium content in the blood is required.

Combinations requiring special attention

Amlodipine:
    inducers of the CYP3A4 isoenzyme (rifampicin, St. John's wort preparations): the plasma concentration of amlodipine decreases;
    potent / moderate inhibitors of CYP3A4, including antifungals of the azole group, protease inhibitors, macrolides (in particular, erythromycin or clarithromycin), tacrolimus, diltiazem, or verapamil: the concentration of amlodipine increases significantly; in elderly patients, the clinical manifestations of these pharmacokinetic abnormalities may be more pronounced, which requires monitoring of their condition and dose adjustment.
Indapamide:
    drugs that can lead to the development of polymorphic ventricular tachycardia such as pirouette, including class IA and III antiarrhythmics (ibutilide, hydroquinidine, quinidine, disopyramide, dofetilide, amiodarone, bretilium tosylate, sotalol), some antipsychotics (levomepromazine, chlorpromazine, cyamoridemoride trifluoperazine), benzamides (sultopride, amisulpride, sulpiride, tiapride), butyrophenones (haloperidol, droperidol), other antipsychotics (pimozide), some other drugs, such as terfenadine, cisapride, bepridil, difemanil, methyl sulphate, metricadine mizolastine, halofantrine, moxifloxacin, pentamidine, astemizole, sparfloxacin, vincamine (intravenous): the risk of hypokalemia increases; if necessary, the potassium content in the blood is corrected, monitoring of the QT interval is required;
    amphotericin B (intravenously), mineral and glucocorticoids (in cases of systemic use), tetracosactide, laxatives that stimulate intestinal motility: the risk of hypokalemia increases (due to an additive effect); constant monitoring of the plasma level of potassium in the blood is required, if necessary, its correction is carried out; patients who receive simultaneously cardiac glycosides need special attention; the use of laxatives that do not stimulate intestinal motility is recommended;
    cardiac glycosides: their toxic effect increases, monitoring of the plasma potassium content in the blood and ECG parameters is required, if necessary, correction of therapy is carried out;
    allopurinol: the risk of hypersensitivity reactions to it increases.
Perindopril:
    hypoglycemic agents: their hypoglycemic effect increases up to the development of hypoglycemia; most likely, a similar effect can be observed during the first weeks of combination therapy, as well as in the presence of impaired renal function;
    diuretics, especially excreting salts / fluids: excessive decrease in blood pressure at the beginning of combined use; when the diuretic is discontinued, fluid / salt loss is replenished before starting perindopril, as well as perindopril is prescribed at a low dose with its gradual further increase, the likelihood of this disorder is reduced; in hypertension, before the use of perindopril, the potassium-sparing diuretic should be canceled (later it can be reappointed), or perindopril is prescribed in a low dose with a further gradual increase; in patients with chronic heart failure, perindopril should be used in a low dose, possibly after reducing the dose of a potassium-sparing diuretic used simultaneously with it; in the first weeks of perindopril use, renal function (creatinine concentration) should be monitored in all cases;
    potassium-sparing diuretics (eplerenone, spironolactone) in the range of daily doses of 12.5-50 mg (with low doses of perindopril): the risk of hyperkalemia (with a possible fatal outcome) increases in patients with chronic heart failure II-IV functional class with left ventricular ejection fraction less than 40% and previously used loop diuretics and ACE inhibitors; if the recommendations regarding this combination of drugs are not followed, the likelihood of developing such a violation increases; before starting combined therapy, you need to make sure that there is no hyperkalemia and impaired renal function; recommended regular monitoring of the concentration of potassium and creatinine in the blood (in the first month of treatment - weekly, then - once a month).
Perindopril + indapamide:
    non-steroidal anti-inflammatory drugs: the antihypertensive effect may be reduced; combined use can worsen renal function, including the development of acute renal failure and an increase in serum potassium in the blood, especially with initially reduced renal function; increased caution is required when prescribing the drug to elderly patients; patients should be provided with an adequate amount of fluid, during the entire period of therapy, regular monitoring of renal function is required;
    baclofen: the antihypertensive effect may be enhanced; control of blood pressure and renal function is necessary, dose adjustment of antihypertensive drugs may be required.

Combinations requiring attention

Amlodipine:
    simvastatin at a dose of 80 mg (combined use with several doses of 10 mg amlodipine): a significant increase in the concentration of simvastatin (in comparison with monotherapy); the daily dose of simvastatin should be reduced to 20 mg;
    antiviral agents (ritonavir): plasma concentrations of amlodipine increase;
    lithium preparations: manifestations of their neurotoxicity (in the form of nausea, vomiting, diarrhea, ataxia, tremor, ringing in the ears) may increase.
Indapamide:
    metformin: the likelihood of lactic acidosis increases; combination therapy is not recommended in cases where the plasma creatinine level exceeds 15 and 12 mg / l in men and women, respectively;
    iodine-containing contrast agents: the risk of developing acute renal failure increases, which is associated with dehydration of the body while taking diuretics; compensation for fluid loss is required;
    calcium salts: the development of hypercalcemia associated with a decrease in calcium excretion by the kidneys is likely;
    cyclosporine: an increase in the plasma concentration of creatinine without changing the concentration of cyclosporine, even in the case of normal sodium and water ions.
Perindopril:
    nitroglycerin, other nitrates or other vasodilators: additional lowering of blood pressure;
    allopurinol, cytostatic and immunosuppressive agents, corticosteroids (with systemic use) and procainamide: the risk of leukopenia increases;
    some means for general anesthesia: the antihypertensive effect is enhanced;
    thiazide and loop diuretics (in high doses): probably the development of arterial hypotension (associated with hypovolemia);
    gliptins (linagliptin, sitagliptin, saxagliptin, vildagliptin): the risk of angioedema increases, which is associated with the suppression of DPP-IV (dipeptidyl peptidase-4) activity by gliptin;
    sympathomimetics: the antihypertensive effect of perindopril may be weakened;
    gold preparations (sodium aurothiomalate): the development of a complex of symptoms of nitritic reactions, including hyperemia of the skin of the face, nausea, vomiting and arterial hypotension.
Perindopril + indapamide + amlodipine (Triplixam):
    antipsychotics, tricyclic antidepressants: the hypotensive effect increases, the risk of orthostatic hypotension increases (associated with an additive effect);
    other antihypertensive drugs: the antihypertensive effect may increase, which contributes to an additional decrease in blood pressure;
    tetracosactide, corticosteroids: the antihypertensive effect is reduced (associated with the retention of sodium ions and fluid due to the effects of corticosteroids).

Terms and conditions of storage

Store at temperatures up to 25 ° C. Keep out of the reach of children.
Shelf life is 2 years.

Reviews about Triplixam

Reviews about Triplixam in most cases are positive. It is noted that the drug is highly effective. The development of adverse reactions is rarely reported, even with prolonged therapy. The cost is assessed as acceptable.

Terms of sell

You don't need a prescription to buy Triplixam.