Prestance, pills 10mg+5mg, 30pcs

Composition

Active ingredients:  

perindopril arginine;

amlodipine bezylate;

Auxiliary substances:

MCC;

lactose monohydrate;

magnesium stearate;

colloidal anhydrous silicon dioxide.

Pharmacological action

Prestans-calcium channel blocker, ACE inhibitor, antihypertensive.

Pharmacodynamics

Perindopril

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (an ACE inhibitor). ACE, or kininase II, is an exopeptidase that performs both the conversion of angiotensin I to the vasoconstrictor angiotensin II, and the destruction of bradykinin, which has a vasodilating effect, to an inactive heptapeptide.

Since ACE inhibits bradykinin, inhibition of ACE is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin systems, while the PG system is also activated.

Perindopril has a therapeutic effect due to its active metabolite, perindoprilat. Other metabolites have no inhibitory effect on ACE in vitro.

Arterial hypertension. Perindopril is a drug for the treatment of arterial hypertension of any severity. Against the background of its use, there is a decrease in both sBP and ABP in the supine and standing positions.

Perindopril reduces OPSS, which leads to a decrease in elevated blood pressure and an improvement in peripheral blood flow without changing the heart rate.

As a rule, taking perindopril increases renal blood flow, but the glomerular filtration rate does not change.

The antihypertensive effect of the drug reaches a maximum in 4-6 hours after a single oral use and persists for 24 hours.

Antihypertensive effect 24 hours after a single oral dose is about 87-100% of the maximum antihypertensive effect.

Decline HELL is achieved quickly enough.

The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal symptoms.

Perindopril has a vasodilating effect, helps restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

Stable coronary artery disease. The efficacy of perindopril in patients with stable coronary heart disease without clinical symptoms of chronic heart failure (12,218 patients over 18 years of age) was studied in a 4-year study (EUROPA).90% of the study participants had previously had an acute myocardial infarction or revascularization procedure.

Perindopril tretbutylamine therapy at a dose of 8 mg / day (equivalent to 10 mg of perindopril arginine) resulted in a significant reduction in the absolute risk of complications by 1.9%, in patients who had previously had a myocardial infarction or revascularization procedure, the absolute risk reduction was 2.2% compared with the placebo group.

Amlodipine

Amlodipine — BMCC, a dihydropyridine derivative. Amlodipine inhibits the transmembrane transfer of calcium ions to cardiomyocytes and smooth muscle cells of the vascular wall.

The antihypertensive effect of amlodipine is due to a direct effect on the smooth muscle cells of the vascular wall. It is established that amlodipine:

• causes dilation of peripheral arterioles, reducing OPSS (afterload), since the HRSP does not change, and the myocardial oxygen demand decreases;
• causes dilation of coronary arteries and arterioles in both ischemic and intact zones. In patients with Prinzmetal angina, coronary blood flow is improved.

In patients with arterial hypertension, taking amlodipine once a day provides a clinically significant reduction in the risk of hypertension. Blood pressure in standing and lying positions for 24 hours. The antihypertensive effect develops slowly, and therefore the development of acute arterial hypotension is uncharacteristic.

In patients with angina pectoris, taking amlodipine once a day increases exercise tolerance, delays the onset of angina attacks and ST-segment ischemic depression, and also reduces the frequency of angina attacks and the consumption of nitroglycerin (short-acting forms).

Amlodipine does not affect the lipid profile and does not cause changes in the lipid-lowering parameters of blood plasma. The drug can be used in patients with concomitant bronchial asthma, diabetes mellitus and gout.

IHD

The results of the efficacy assessment indicate that amlodipine therapy is characterized by fewer cases of hospitalization for angina pectoris and revascularization procedures in patients with CHD.

Heart failure

The results of hemodynamic studies, as well as the results of clinical studies involving patients with NYHA functional class II–IV chronic heart failure, demonstrated that amlodipine does not lead to clinical deterioration, based on exercise tolerance, left ventricular ejection fraction, and clinical symptomatology.

In patients with NYHA functional Class III–IV chronic heart failure, while taking digoxin, diuretics, and ACE inhibitors, it has been shown that taking amlodipine does not lead to an increased risk of death or mortality and morbidity associated with heart failure.

The results of long-term studies in patients with chronic heart failure of NYHA functional class III and IV without clinical symptoms of CHD or objective data indicating the presence of CHD, while taking stable doses of ACE inhibitors, cardiac glycosides and diuretics showed that taking amlodipine does not affect the mortality rate from cardiovascular diseases. In this population of patients, the use of amlodipine was accompanied by an increase in the number of reports of the development of pulmonary edema.

Study of the effectiveness of preventive treatment of myocardial infarction

The efficacy and safety of amlodipine at a dose of 2.5–10 mg/day, the apflizinopril inhibitor at a dose of 10-40 mg/day, and the thiazide diuretic chlortalidone at a dose of 12.5–25 mg/day as a first-line drug was studied in a 5-year ALLHAT study (involving 33,357 patients aged 55 years and older) in patients with mild or moderate arterial hypertension and at least one of the additional risk factors for coronary complications, such as such as a myocardial infarction or stroke that occurred more than 6 months prior to inclusion in the study, or other confirmed cardiovascular disease of atherosclerotic origin; diabetes mellitus; HDL cholesterol concentration less than 35 mg/dl; left ventricular hypertrophy according to ECG or echocardiography; smoking.

The main criterion for evaluating effectiveness is a combined indicator of the frequency of deaths from CHD and the frequency of non-fatal myocardial infarction. There were no significant differences between the amlodipine and chlortalidone groups according to the main evaluation criterion. The incidence of heart failure in the amlodipine group was significantly higher than in the chlortalidone group — 10.2 and 7.7%, respectively, and the overall mortality rate in the amlodipine and chlortalidone groups did not differ significantly.

Perindopril, amlodipine

Efficacy with long-term use of amlodipine in combination with perindopril and atenolol in combination with bendroflumethiazide in patients aged 40 to 79 years with arterial hypertension and at least 3 of the additional risk factors: left ventricular hypertrophy according to ECG or echocardiography; type 2 diabetes mellitus; peripheral arterial atherosclerosis; previous stroke or transient ischemic attack; male sex; age 55 years and older; microalbuminuria or proteinuria; smoking; total cholesterol/HDL cholesterol ratio ≥6; early development of CHD in the next of kin was studied in the ASCOT-BPLA study.

The main criterion for evaluating efficacy is a combined indicator of the frequency of non-fatal myocardial infarction (including painless) and fatal outcomes of CHD.

The frequency of complications provided for by the main evaluation criterion in the amlodipine/perindopril group was 10% lower than in the atenolol/bendroflumethiazide group, but this difference was not statistically significant. In the amlodipine/perindopril group, there was a significant reduction in the incidence of complications provided for by additional efficacy criteria (except for fatal and non-fatal heart failure).

Pharmacokinetics

The amount of absorption of perindopril and amlodipine when using the drug Prestans does not significantly differ from that when using monopreparations.

Perindopril

When taken orally, perindopril is rapidly absorbed, _cmax in blood plasma is reached within 1 h. T_1/2 of the blood plasma is 1 h.

Perindopril has no pharmacological activity. Approximately 27% of the total amount of oral perindopril enters the bloodstream as the active metabolite of perindoprilat. In addition to perindoprilat,5 more metabolites are formed that do not have pharmacological activity. _{Cmax of}perindoprilat in blood plasma is reached 3-4 hours after oral use of perindopril. Food intake slows down the conversion of perindopril to perindoprilate, thus affecting bioavailability. Therefore, the drug should be taken once a day, in the morning, before meals.

There is a linear dependence of the concentration of perindopril in blood plasma on its dose. The_{vd of}free perindoprilate is approximately 0.2 l / kg. The association of perindoprilat with plasma proteins, mainly with ACE, is about 20% and is dose-dependent.

Perindoprilat is eliminated from the body by the kidneys. The final T_1/2 of the free fraction is about 17 hours, so the equilibrium state is reached within 4 days.

The elimination of perindoprilat is slowed in the elderly, as well as in patients with heart and renal insufficiency (see “Method of use and doses”). Therefore, in these groups of patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

The dialysis clearance of perindoprilat is 70 ml / min

. The pharmacokinetics of perindopril are impaired in patients with cirrhosis of the liver: its hepatic clearance decreases by 2 times. However, the amount of perindoprilat produced does not decrease, which does not require dose adjustment (see” Dosage and use “and”Special Instructions”).

Amlodipine

After oral use, amlodipine is slowly absorbed from the gastrointestinal tract. Food intake does not affect the bioavailability of amlodipine.

_{Cmax of}amlodipine in blood plasma is reached 6-12 hours after oral use. Absolute bioavailability is about 64-80%, Vd-about 21 l / kg. In vitro studies have shown that about 97.5% of circulating amlodipine is bound to plasma proteins.

The final T_1/2 of amlodipine from the blood plasma is 35-50 hours, which allows you to take the drug once a day. Amlodipine is metabolized in the liver to form inactive metabolites, with 10% of the dose of amlodipine being excreted unchanged and 60% as metabolites by the kidneys. Amlodipine is not eliminated from the body by dialysis.

The time from taking the drug to reaching the_cmax of amlodipine does not differ in elderly and younger patients. In elderly patients, there is a slowdown in the clearance of amlodipine, which leads to an increase in AUC. The increase in AUC and T_1/2 in patients with chronic heart failure (CHF) corresponds to the expected value for this age group.

In patients with impaired renal function, changes in the concentration of amlodipine in blood plasma do not correlate with the degree of renal failure. A slight increase in T_{1/2 is possible}.

Data on the use of amlodipine in patients with hepatic insufficiency are limited. In patients with hepatic insufficiency, there is a decrease in the clearance of amlodipine, which leads to an increase in T_1/2 and AUC by approximately 40-60%.

Indications

Arterial hypertension and / or coronary artery disease: stable angina pectoris in patients requiring perindopril and amlodipine therapy.

Use during pregnancy and lactation

Pregnancy

The drug is contraindicated for use during pregnancy.

When planning pregnancy, the drug should be discontinued and other antihypertensive agents approved for use during pregnancy should be prescribed. If pregnancy occurs, you should immediately stop taking Prestans and, if necessary, prescribe another antihypertensive therapy.

It is known that the effect of ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to impaired development (decreased renal function, oligohydramnios, slowing of ossification of the skull bones) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia).

If the patient received ACE inhibitors during the second or third trimester of pregnancy, it is recommended to perform ultrasound of the newborn to assess the condition of the skull and kidney function.

Newborns whose mothers received ACE inhibitors during pregnancy should be closely monitored due to the risk of hypotension, oliguria, and hyperkalemia (see “Contraindications” and “Special Instructions”).

Amlodipine

In experimental studies, the fetotoxic and embryotoxic effects of the drug have not been established, but use during pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

In some patients treated with slow calcium channel blockers (BMCC), a reversible decrease in sperm motility was observed. There is insufficient clinical evidence regarding the potential effect of amlodipine on reproductive function.

Breast-feeding period

Amlodipine

There are no data indicating the excretion of amlodipine in breast milk. However, other BMCC derivatives of dihydropyridine are known to be excreted in breast milk. In this regard, if it is necessary to prescribe the drug amlodipine during lactation, the question of stopping breastfeeding should be decided.

Perindopril

Due to the lack of information regarding the use of perindopril during breast-feeding, the use of perindopril is not recommended, it is preferable to adhere to an alternative treatment with a more studied safety profile during breast-feeding.

Prestance

It is not recommended to take Prestans during lactation due to the lack of appropriate clinical experience with the use of perindopril and amlodipine both in monotherapy and as part of combination therapy.

If it is necessary to take the drug during lactation, you should stop breastfeeding.

Contraindications

Perindopril

• hypersensitivity to perindopril or other ACE inhibitors;
• a history of angioedema (angioedema) (including when taking other ACE inhibitors);
• hereditary / idiopathic angioedema;
• age up to 18 years (efficacy and safety have not been established).

Amlodipine

• increased sensitivity to amlodipine and other derivatives of dihydropyridine;
• severe hypotension (SBP less than 90 mm Hg. calendar);
• shock, including cardiogenic;
• obstruction of the output tract of the left ventricle (e. g., clinically significant aortic stenosis);
• hemodynamically unstable heart failure after acute myocardial infarction;
• the age of 18 years (effectiveness and safety not established).

Prestans

• hypersensitivity to excipients included in the drug;
• renal insufficiency (creatinine clearance
• under 18 years of age (efficacy and safety have not been established);
• hereditary lactose intolerance, lactase insufficiency and glucose-galactose malabsorption.

With caution: renal artery stenosis (including bilateral), single functioning kidney, liver failure, renal failure, systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), immunosuppressant therapy, allopurinol, procainamide (risk of neutropenia, agranulocytosis), reduced BCC (diuretics, salt-free diet, vomiting, diarrhea), atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure, concomitant use of dantrolene, estramustine, potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes and lithium preparations, hyperkalemia, surgery/general anesthesia, the elderly, hemodialysis using high-flow membranes (for example, AN69®), desensitizing therapy, apheresis LDL, aortic stenosis / mitral stenosis/hypertrophic obstructive cardiomyopathy, use in patients of black race, CHF of non-ischemic etiology of NYHA functional class III–IV.

Side effects

From the blood, hematopoietic and lymphatic system: very rarely — leukopenia/neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency, decreased hemoglobin and hematocrit.

From the immune system: infrequently-allergic reactions.

Metabolic disorders: very rarely-hyperglycemia; unspecified frequency-hypoglycemia.

From the central nervous system: often-drowsiness (especially at the beginning of treatment), dizziness (especially at the beginning of treatment), headache, paresthesia, vertigo; infrequently — insomnia, mood lability (including anxiety), sleep disturbance, tremor, hypesthesia, depression, fainting; rarely — confusion; very rarely — peripheral neuropathy, hypertension.

From the side of the visual organ: often-visual disturbances (including diplopia).

From the side of the hearing organ: often-tinnitus.

From the CCC side: often — palpitation of the heart, flushes of blood to the skin of the face, marked decrease in blood pressure. Very rarely — angina pectoris, myocardial infarction, possibly due to an excessive decrease in blood pressure. Blood pressure in high-risk patients (see “Special instructions”), arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to an excessive decrease in blood pressure. Blood pressure in high-risk patients (see “Special instructions”), vasculitis.

Respiratory system disorders: often-shortness of breath, cough; infrequently-rhinitis, bronchospasm; very rarely-eosinophilic pneumonia.

From the digestive system: often-abdominal pain, nausea, vomiting, dyspepsia, diarrhea, constipation; infrequently-changes in the rhythm of defecation, dryness of the oral mucosa; very rarely-pancreatitis, gum hyperplasia, gastritis.

Liver and biliary tract disorders: very rarely-hepatitis, jaundice, increased activity of liver enzymes (most often-in combination with cholestasis), cytolytic or cholestatic hepatitis (see “Special instructions”).

From the side of the skin and subcutaneous fat: often-pruritus of the skin, exanthema; infrequently-angioedema of the face, extremities, lips, mucous membranes, tongue, vocal folds and / or larynx (see “Special instructions”), alopecia, hemorrhagic rash, discoloration of the skin, increased sweating, urticaria; very rarely — angioedema, erythema multiforme, Stevens-Johnson syndrome; exfoliative dermatitis, photosensitivity.

Musculoskeletal and connective tissue disorders: often-muscle spasms, swelling of the lower legs; infrequently-arthralgia, myalgia, back pain.

From the side of the kidneys and urinary tract: infrequently-impaired urination, nocturia, frequent urination, impaired renal function; very rarely-acute renal failure.

From the side of the reproductive system and mammary glands: infrequently — impotence, gynecomastia.

Common disorders and symptoms: often — edema, asthenia, increased fatigue; infrequently-chest pain, malaise, pain.

Laboratory parameters: infrequently-an increase in body weight, a decrease in body weight; rarely-an increase in the concentration of bilirubin; unspecified frequency-an increase in the concentration of urea and creatinine in the blood serum, hyperkalemia.

Additional information on amlodipine: isolated cases of extrapyramidal syndrome have been reported.

Interaction

Perindopril

1. Not recommended drug combinations

Potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes:despite the fact that the potassium content in the blood serum remains within the normal range, hyperkalemia may occur in some patients when using perindopril. Potassium-sparing diuretics (for example, spironolactone and its derivative-eplerenone, triamterene, amiloride), potassium preparations and potassium-containing food salt substitutes can lead to a significant increase in the content of potassium in the blood serum. In this regard, the simultaneous use of an ACE inhibitor and the above drugs is not recommended (see “Special instructions”). If concomitant use of an inhibitor is necessary (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.

Lithium preparations: with the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the content of lithium in blood plasma and associated toxic effects may occur. Concomitant use of perindopril and lithium preparations is not recommended. If such therapy is necessary, regular monitoring of the lithium content in the blood plasma is necessary (see “Special instructions”).

Estramustin: concomitant use of estramustine with ACE inhibitors is associated with an increased risk of angioedema.

2. Combination of Drugs requiring special attention

NSAIDs, including high doses of acetylsalicylic acid (more than 3 g / day): concomitant use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) may lead to a decrease in the antihypertensive effect of ACE inhibitors. Concomitant use of ACE inhibitors and NSAIDs can lead to deterioration of renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and carefully monitor kidney function, both at the beginning of treatment and during treatment.

Hypoglycemic agents (oral hypoglycemic agents, sulfonylureas and insulin): ACE inhibitors may increase the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. Hypoglycemia is very rare (probably due to an increase in glucose tolerance and a decrease in the need for insulin).

3. Drug combinations that require attention

Diuretics (thiazide and loop): patients receiving diuretics, especially those with excessive fluid and/or electrolyte excretion, may experience a significant decrease at the start of ACE inhibitor therapy. Blood pressure, the risk of which can be reduced by discontinuing the diuretic, introducing an increased amount of fluid and / or table salt, as well as prescribing perindopril in a low dose with a further gradual increase.

Sympathomimetics: may weaken the antihypertensive effect of ACE inhibitors.

Gold preparations: when using ACE inhibitors, including perindopril, patients receiving injectable gold preparations (sodium aurothiomalate), a symptom complex was described, including facial skin hyperemia, nausea, vomiting, and hypotension.

Allopurinol, cytostatic and immunosuppressive agents, corticosteroids (for systemic use) and procainamide: concomitant use with ACE inhibitors may be associated with an increased risk of leukopenia.

General anesthesia products: concomitant use of ACE inhibitors and general anaesthetics may lead to an increased antihypertensive effect.

Amlodipine

1. Not recommended drug combinations

Dantrolene (intravenous use): in laboratory animals, cases of ventricular fibrillation with a fatal outcome and collapse were noted against the background of verapamil and intravenous dantrolene use, accompanied by hyperkalemia. Due to the risk of hyperkalemia, concomitant use of BMCC, including amlodipine, should be excluded in patients subject to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

2. Combination of Medicinal products that require special attention

Inducers of cytochrome CYP3A4 isoenzymes. There are no data on the effect of inducers of the CYP3A4 isoenzyme on amlodipine. Concomitant use of inducers of the isoenzyme CYP3A4 (for example, rifampicin, St. John’s wort preparations) may lead to a decrease in the plasma concentration of amlodipine. Caution should be exercised when concomitantly using amlodipine and inducers of microsomal oxidation.

Inhibitors of cytochrome CYP3A4 isoenzymes. Concomitant use of amlodipine and potent or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungal drugs, macrolides (for example, erythromycin or clarithromycin), verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. The clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. Therefore, it may be necessary to monitor the clinical condition and adjust the dose.

3. Combination of Personal information that requires attention

Amlodipine enhances the antihypertensive effect of antihypertensive drugs.

Other combinations BOS

In clinical drug interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine.

Concomitant use of amlodipine and consumption of grapefruit or grapefruit juice is not recommended, due to the possible increase in the bioavailability of amlodipine in some patients, which, in turn, may lead to increased effects of lowering blood pressure.

Prestance

1. Combination of Medicinal products that require special attention:

Baclofen: it is possible to increase the antihypertensive effect. Blood pressure and renal function should be monitored, and the dose of amlodipine should be adjusted if necessary.

2. A combination of medications that requires attention:

Antihypertensive agents (e. g. beta-blockers) and vasodilators: it is possible to increase the antihypertensive effect of perindopril and amlodipine. Caution should be exercised when prescribing concomitantly with nitroglycerin, other nitrates or other vasodilators, as this may lead to an additional decrease in blood pressure.

Corticosteroids (mineralocorticosteroids and corticosteroids), tetracosactide: reduced antihypertensive effect (fluid retention and sodium ions as a result of corticosteroids).

Alpha-blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin): increased antihypertensive effect and increased risk of orthostatic hypotension.

Amifostin: it is possible to increase the hypotensive effect of amlodipine.

Tricyclic Antidepressants/Antipsychotics/General Anaesthetics: increased antihypertensive effect and increased risk of orthostatic hypotension.

How to take it, course of use and dosage

The drug is prescribed orally,1 tablet 1 time a day, in the morning before meals.

Overdose

Amlodipine

Information about amlodipine overdose is limited.

Symptoms: marked decrease Blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including with the development of shock and death).

Treatment: gastric lavage, use of activated charcoal (especially in the first 2 hours after overdose), maintenance of the cardiovascular system and respiratory system, elevated position of the limbs, control of BCC and diuresis, symptomatic and supportive therapy, intravenous use of calcium gluconate and dopamine. Hemodialysis is ineffective. If there is a significant decrease in AP, the patient should be monitored in the cardiology intensive care unit. In the absence of contraindications, vasoconstrictors can also be used to restore vascular tone.

Perindopril

Data on perindopril overdose are limited.

Symptoms: significant reduction Blood pressure, shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitation, bradycardia, dizziness, restlessness and cough.

Treatment: with a significant reduction Blood pressure should be transferred to a supine position with raised legs, if necessary, correction of hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Intravenous use of catecholamines is also possible. Hemodialysis can remove perindopril from the systemic circulation (see “Special instructions”). If bradycardia is resistant to therapy, it may be necessary to install an artificial pacemaker. Dynamic monitoring of the physical state, concentration of creatinine and blood electrolytes is required.

Emergency measures are limited to removing the drug from the body: gastric lavage and / or prescribing activated carbon, followed by restoring the water-electrolyte balance.

Special instructions

Perindopril

Hypersensitivity/angioedema

When taking ACE inhibitors, including perindopril, in rare cases, angioedema of the face, limbs, lips, mucous membranes, tongue, vocal folds and/or larynx may develop (see “Side effects”). If symptoms appear, the drug should be stopped immediately and the patient should be monitored 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 can be used to treat the symptoms.

Angioedema accompanied by laryngeal edema can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms occur, epinephrine (epinephrine)should be administered immediately n / a and / or ensure airway patency. The patient should be under medical supervision until complete and persistent disappearance of symptoms.

Patients with a history of angioedema that is not associated with ACE inhibitors may have an increased risk of developing angioedema when taking drugs in this group (see “Contraindications”).

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases, without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis is established by computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappear after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, differential diagnosis should take into account the possibility of developing angioedema of the intestine (see “Side effects”).

Anaphylactoid reactions during LDL apheresis

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

Anaphylactoid reactions during desensitization

There are isolated reports of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy (for example, with hymenopteran venom). In these patients, the anaphylactoid reaction was avoided by temporarily stopping ACE inhibitors, and if the drug was accidentally taken, the anaphylactoid reaction occurred again.

Neutropenia/agranulocytosis / thrombocytopenia/anemia

Neutropenia/agranulocytosis, thrombocytopenia, and anemia may occur while taking ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other aggravating factors. Perindopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.

Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor white blood cells in the blood. Patients should inform the doctor about any signs of infectious diseases (for example, sore throat, fever).

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients without concomitant diseases. Risk of excessive decline ADP is elevated in patients with reduced BCC, which can be observed against the background of diuretic therapy, with a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe arterial hypertension with high renin activity (see “Interaction”). In patients with an increased risk of developing symptomatic hypotension, blood pressure, renal function, and serum potassium should be carefully monitored during Prestans therapy.

This approach is also used in patients with angina pectoris and cerebrovascular diseases, in which severe arterial hypotension can lead to myocardial infarction or impaired cerebral circulation.

In case of hypotension, the patient should be placed in a supine position with raised legs. If necessary, the BCC should be replenished by intravenous use of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further use of the drug. After recovery of BCC and blood pressure, treatment can be continued.

Mitral stenosis/aortic stenosis/Hypertrophic obstructive cardiomyopathy

Prestans, like other ACE inhibitors, should be used with caution in patients with left ventricular exit tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.

Impaired renal function

In patients with renal insufficiency (creatinine clearance less than 60 ml/min), individual dose selection of perindopril and amlodipine is recommended. Such patients need regular monitoring of serum potassium and creatinine (see “Side effects”).

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during therapy with ACE inhibitors, an increase in serum urea and creatinine concentrations may occur, usually with discontinuation of therapy. More often, this effect is observed in patients with renal insufficiency. The additional presence of renovascular hypertension leads to an increased risk of severe hypotension and renal failure in these patients.

In some patients with arterial hypertension without signs of renal vascular damage, an increase in the concentration of urea and creatinine in the blood serum is possible, especially when perindopril is co-administered with a diuretic, usually insignificant and transient. More often, this effect is observed in patients with previous renal impairment.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. 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 jaundice or a significant increase in the activity of liver enzymes occurs while taking ACE inhibitors, you should stop taking the drug (see “Side effect”).

Ethnic differences

Patients of the black race are more likely than those of other races to develop angioedema while taking ACE inhibitors.

Perindopril, like other ACE inhibitors, may have a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the black race are more likely to have low renin activity.

Cough

During ACE inhibitor therapy, a dry cough may occur. Cough persists for a long time against the background of taking drugs of this group and disappears after their cancellation. If a patient has a dry cough, you should be aware of the possible iatrogenic nature of this symptom.

Surgical intervention/General anesthesia

The use of ACE inhibitors in patients undergoing extensive surgery and/or general anesthesia may lead to a marked decrease in the risk of angiotensin-converting enzyme activity. Blood pressure, if general anesthesia agents with a hypotensive effect are used.This is due to blocking the formation of angiotensin II against the background of a compensatory increase in renin activity. If the development of arterial hypotension is associated with the described mechanism, the volume of circulating plasma should be increased. It is recommended to warn the surgeon / anesthesiologist that the patient is taking ACE inhibitors and stop taking the drug 24 hours before surgery.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, age over 70 years, diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of CHF, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that contribute to an increase in the content of potassium in blood plasma (for example, heparin). The use of potassium preparations, potassium-sparing diuretics, and potassium-containing substitutes for table salt can lead to a significant increase in the blood potassium content, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal, cardiac arrhythmias. If simultaneous use of perindopril and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of serum potassium (see “Interaction”).

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral use or insulin, during the first month of therapy, it is necessary to carefully monitor the concentration of glucose in the blood (see “Interaction”).

Amlodipine

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

Heart failure

Patients with heart failure should be treated with caution. When using amlodipine in patients with chronic heart failure of NYHA functional class III and IV, pulmonary edema may develop. BMCC, including amlodipine, should be used with caution in patients with chronic heart failure, due to the possible increase in the risk of adverse events from CVD and mortality.

Liver failure

In patients with hepatic impairment, T_1/2 and AUC of amlodipine are increased. Amlodipine should be started at the lowest possible dose and precautions should be taken both at the beginning of treatment and when increasing the dose. Patients with severe hepatic insufficiency should increase the dose gradually, ensuring careful monitoring of the clinical condition.

Elderly patients

In elderly patients, T_{1/2 may increase} and clearance of amlodipine may decrease. Dose changes are not required, but more careful monitoring of patients in this category is necessary.

In patients with impaired renal function, monitoring of the condition is necessary.

Kidney failure

Patients with renal insufficiency can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure. Amlodipine is not eliminated from the body by dialysis.

Prestance

Auxiliary substances

Due to the presence of lactose in the composition of the drug, the drug should not be prescribed to patients with hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Influence on the ability to drive a car and perform work that requires increased speed of physical and mental reactions. Although no adverse effects on the ability to drive vehicles or other complex mechanisms were observed while taking Prestans, however, due to a possible excessive decrease in blood pressure, dizziness, drowsiness and other adverse reactions, caution should be exercised in these situations, especially at the beginning of treatment and when increasing the dose.

Composition

Tablet Form of production

Storage conditions

No special storage conditions are required

Shelf life

2 years

Active ingredient

Amlodipine, Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension, Angina