Prestans - instructions for use, dose, side effects, contraindications

1 tablet 5 mg + 5 mg: contains active substances perindopril arginine 5 mg, corresponds to 3.395 mg of perindopril and amlodipine besylate 6.935 mg corresponds to 5 mg of amlodipine.

1 tablet 10 mg + 10 mg: contains active substances perindopril arginine 10 mg, corresponds to 6.79 mg perindopril and amlodipine besylate 13.87 mg corresponds to 10 mg of amlodipine.

1 tablet 5 mg + 10 mg: contains active substances perindopril arginine 5 mg, corresponds to 3.395 mg of perindopril and amlodipine besylate 13.87 mg corresponds to 10 mg of amlodipine.

1 tablet of 10 mg + 5 mg: contains active substances perindopril arginine 10 mg, corresponds to 6.79 mg perindopril and amlodipine besylate 6.935 mg corresponds to 5 mg of amlodipine.

Excipients: cellulose microcrystalline 26/52/52/52 mg, lactose monohydrate 65,233 / 130,466 / 135,466 / 137,401 mg, magnesium stearate 0.52 / 1.04 / 1.04 / 1.04 mg, silicon dioxide colloidal anhydrous 0.312 / 0.624 / 0.624 / 0.624 mg.

Description:

Tablets 5 mg + 5 mg: oblong biconvex tablets of white color, engraved with "5/5" on one side and the company logo on the other.

Tablets 5 mg + 10 mg: square biconvex tablets of white color, engraved "5/10" on one side and the company logo on the other.

Tablets 10 mg + 10 mg: round biconvex tablets of white color, engraved "10/10" on one side and the company logo on the other.

Tablets 10 mg + 5 mg: triangular biconvex tablets of white color, engraved "10/5" on one side and the company logo on the other.

Pharmacotherapeutic group: hypotensive combined agent (angiotensin-converting enzyme (ACE) inhibitor + "slow" calcium channel blocker (BCCC)).

ATX: & nbsp

C.09.A.A.04 Perindopril

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Perindopril

Perindopril is an inhibitor of the enzyme converting angiotensin I to angiotensin II (an ACE inhibitor). An angiotensin-converting enzyme, or kininase II, is an exopeptidase that carries out both the conversion of angiotensin I into a vasoconstrictor substance, angiotensin II, and the destruction of bradykinin, which has a vasodilating action, to an inactive heptapeptide.

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

Perindopril has a therapeutic effect due to the 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 systolic and diastolic arterial pressure (BP) in the "lying" and "standing" positions.

Perindopril reduces the overall peripheral vascular resistance, which leads to a decrease in elevated blood pressure and an improvement in peripheral blood flow without changing the heart rate (heart rate).

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

Antihypertensive effect of the drug reaches a maximum in 4-6 hours after a single oral intake and is maintained for 24 hours.

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

Decrease in blood pressure is achieved quickly enough.

The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachycardia. Termination of treatment does not cause withdrawal syndrome. 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 ischemic heart disease (CHD)

The efficacy of perindopril in patients (12218 patients older than 18 years) with stable coronary artery disease without clinical symptoms of chronic heart failure was studied in a 4-year study (EUROPA). 90% of study participants had previously suffered an acute myocardial infarction or revascularization procedure.

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

Amlodipine

Amlodipine- BCCI, derivative dihydropyridine. Amlodipine inhibits the transmembrane transition of calcium ions to cardiomyocytes and smooth muscle cells of the vascular wall.

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

- causes the peripheral arterioles to expand, decreasing the total peripheral resistance of the vessels (afterload), since heart rate does not change, and myocardial oxygen demand decreases.

- causes the expansion of the coronary arteries and arterioles both in the ischemic and intact zones. In patients with Prinzmetal angina, coronary blood flow is improved.

In patients with arterial hypertension (AH), amlodipine once a day provides a clinically significant decrease in blood pressure in the "standing" and "lying" for 24 hours. Antihypertensive effect develops slowly, and therefore, the development of acute arterial hypotension is uncharacteristic.

In patients with angina, receiving amlodipine once a day increases tolerance to physical activity, delays the onset of an attack of angina and "ischemic" depression segment ST, and also reduces the incidence of angina attacks and the intake of nitroglycerin (short-acting forms).

Amlodipine has no effect on the lipid profile and does not cause changes in lipid-lowering plasma parameters. The drug can be used in patients with concomitant bronchial asthma, diabetes and gout.

Ischemic heart disease (CHD)

The results of the efficacy evaluation suggest that amlodipine intake is characterized by fewer hospitalizations for angina and revascularization procedures in patients with ischemic heart disease.

Heart failure

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

In patients with chronic heart failure III-IV functional class NYHA, against the background of taking digoxin, diuretics and ACE inhibitors, it was shown that the use of amlodipine does not lead to an increased risk of mortality or mortality and morbidity associated with heart failure.

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

The study of the effectiveness of preventive treatment of myocardial infarction:

The efficacy and safety of the use of amlodipine in a dose of 2.5-10 mg / day, an inhibitor of ACE lisinopril 10-40 mg / day and thiazide diuretic chlorthalidone at a dose of 12.5-25 mg / day as a "first line" drug was studied in 5-year study ALLHAT (with the participation of 33,357 patients aged 55 years and over) in patients with mild or moderate hypertension and at least one of the additional risk factors for coronary events such as: myocardial infarction or stroke, which was carried out more than 6 months before inclusion in a study, or other confirmed cardiovascular disease of atherosclerotic origin; diabetes; concentration high-density lipoprotein cholesterol (HDL-C) less than 35 mg / dL; hypertrophy of the left ventricle according to electrocardiography or echocardiography; smoking.

The main criterion for assessing efficacy is a combined index of the frequency of deaths from ischemic heart disease and the incidence of non-fatal myocardial infarction. There were no significant differences between the groups of amlodipine and chlorthalidone according to the main evaluation criterion. The incidence of heart failure in the amlodipine group was significantly higher than in the chlorthalidone group - 10.2% and 7.7%, respectively, the overall death rate in the amlodipine and chlorthalidone group did not differ significantly.

Perindopril, amlodipine

Efficacy with long-term use of amlodipine incombination with perindopril and atenolol in combination with bendroflumethiazide patients aged 40 to 79 years with hypertension and at least 3 of additional risk factors: left ventricular hypertrophy on echocardiogram or electrocardiogram data; type 2 diabetes mellitus; atherosclerosis of peripheral arteries; previously suffered stroke or transient ischemic attack; male; age 55 years and older; microalbuminuria or proteinuria; smoking; total cholesterol / HDL-C> 6; early development of IHD in the immediate relatives was studied in the study ASCOT-BPLA.

The main criterion for evaluating efficacy is a combined indicator of the incidence of non-fatal myocardial infarction (including painless) and lethal outcomes of IHD. The incidence of complications provided 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 additional criteria of effectiveness (except fatal and nonfatal heart failure).

Pharmacokinetics:

The amount of absorption of perindopril and amlodipine in the use of the preparation Prestanas does not differ significantly from that in application of monopreparations.

Perindopril

Ingestion perindopril quickly absorbed, the maximum concentration in the blood plasma is reached within 1 hour. Half-life (T1/2) from the blood plasma is 1 hour.

Perindopril does not have pharmacological activity. Approximately 27% of the total amount of perindopril ingested enters the bloodstream as an active metabolite of perindoprilate. In addition to perindoprilata, another 5 metabolites are formed that do not have pharmacological activity. The maximum concentration of perindoprilat in the blood plasma is reached 3-4 hours after ingestion. Eating slows the conversion of perindopril to perindoprilat, thus affecting bioavailability. Therefore, the drug should be taken 1 time per day, in the morning, before eating.

There is a linear dependence of the concentration of perindopril in the blood plasma from its dose. The volume of distribution of free perindoprilata 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 excreted from the body by the kidneys. The final T1/2 free fraction is about 17 hours, so the equilibrium state is reached within 4 days. The excretion of perindoprilate is delayed in the elderly, and patients with cardiac and renal insufficiency (see section "Method of administration and dose"). Therefore, these groups of patients should regularly monitor the concentration of creatinine and potassium in the blood plasma.

The dialytic clearance of perindoprilat is 70 ml / min.

Pharmacokinetics of perindopril broken the patients with cirrhosis of the liver: its hepatic clearance is reduced by 2 times. Nevertheless, the amount of perindoprilat formed does not decrease, which does not require dose adjustment (see the sections "Dosage and Administration" and "Special instructions").

Amlodipine

After oral administration amlodipine slowly absorbed from the gastrointestinal tract (GIT). Food intake does not affect the bioavailability of amlodipine.

The maximum concentration of amlodipine in the blood plasma is reached 6-12 hours after ingestion.Absolute bioavailability is about 64-80%, the volume of distribution is about 21 l / kg. In studies in vitro it was shown that about 97.5% of circulating amlodipine is associated with plasma proteins.

Finite T1/2 Amlodipine from the blood plasma is 35-50 hours, which allows you to take the drug 1 time per day. Amlodipine metabolized in the liver with the formation of inactive metabolites, with 10% of the dose of amlodipine taken out unchanged and 60% at night - in the form of metabolites. Amlodipine is not excreted from the body by dialysis.

The time from taking the drug to reaching the maximum concentration 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 the area under the "concentration-time" curve (AUC). Increase AUC and T1/2 in patients with chronic heart failure (CHF) corresponds to the expected value for this age group.

In patients with impaired renal function, changes in amlodipine concentration in the blood plasma do not correlate with the degree of renal failure.Possible slight increase T1/2.

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

Indications:

Arterial hypertension and / or ischemic heart disease (CHD): stable angina pectoris in patients who require perindopril and amlodipine therapy.

Contraindications:

Perindopril

- Hypersensitivity to perindopril or other ACE inhibitors.

- Angioedema (angioedema) in the anamnesis (including those taking other ACE inhibitors).

- Hereditary / idiopathic angioedema.

- Age up to 18 lay down (effectiveness and safety not established).

Amlodipine

- Hypersensitivity to amlodipine and other derivatives dihydropyridine.

- Heavy arterial hypotension (systolic blood pressure less than 90 mm Hg).

- Shock (including cardiogenic).

- Obstruction of the left ventricular outflow tract (for example, clinically relevant stenosis of the aorta).

- Hemodynamically unstable heart failure after acute myocardial infarction.

- Age to 18 years (effectiveness and safety not established).

Prestans

- Hypersensitivity to the excipients included in the preparation.

- Renal failure (creatinine clearance (CK) less than 60 ml / min).

- Age to 18 years (effectiveness and safety not established).

- Hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Carefully:

Renal artery stenosis (including bilateral), the only functioning kidney, liver failure, renal failure, systemic connective tissue disease (including systemic lupus erythematosus, scleroderma), immunosuppressive therapy, allopurinol, procainamide (risk of neutropenia, agranulocytosis) , decreased volume of circulating blood (BCC) (Diuretics, salt-free diet, vomiting, diarrhea), atherosclerosis, cerebrovascular disease, renovascular hypertension, diabetes, chronic heart failure, simultaneous use of dantrolene, estramustine, potassium-sparing diuretics, potassium preparations, potassium-based salt substitutes food and drugs lithium, hyperkalemia, surgery / anesthesia general, elderly, hemodialysis using high-permeability membranes (for example, AN69®), desensitizing therapy, low-density lipoprotein apheresis (LDL), aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, use in patients Negroid race, CHF of non-ischemic etiology III-IV functional class by classification NYHA.

Pregnancy and lactation:

Pregnancy

The drug is contraindicated for use in pregnancy.

When planning pregnancy, you should cancel the drug and prescribe other antihypertensive drugs that are approved for use in pregnancy. At the onset of pregnancy 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 II and III trimester of gestation may lead to disruption of its development (reduction of renal function, oligohydramnios, slowing ossification of bones of the skull) and the development of complications in the newborn (renal failure, hypotension, hyperkalaemia).

If the patient has received an ACE inhibitor during II or III trimester of pregnancy, it is recommended to conduct ultrasound newborn to assess the status of the skull and renal function.

Newborns whose mothers received ACE inhibitors during pregnancy should be under careful medical supervision because of the risk of developing arterial hypotension, oliguria, and hyperkalemia (see "Contraindications" and "Special instructions").

Amlodipine

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

Have Some patients treated with blockers of "slow" calcium channels noted a reversible decrease in motility of spermatozoa. Clinical data concerning the potential effect of amlodipine on reproductive function is not enough.

Breastfeeding period Amlodipine

There is no evidence of excretion of amlodipine in breast milk. However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk. In this connection, when it is necessary to prescribe the drug amlodipine During the lactation period, the issue of stopping breastfeeding should be addressed.

Perindopril

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

Prestans

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

If you need to take the drug during lactation, you should stop breastfeeding.

Dosing and Administration:

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

The dose of the drug Prestanse is selected after previous titration of the doses of individual components of the drug: perindopril and amlodipine in patients with hypertension and / or ischemic heart disease.

With therapeutic need, the dose of the drug Prestan can be changed or individual doses of individual components can be individually pre-determined.

5 mg perindopril + 5 mg amlodipine OR 5 mg perindopril + 10 mg amlodipine OR 10 mg perindopril + 5 mg amlodipine OR 10 mg perindopril + 10 mg amlodipine.

Special patient groups

Elderly patients and patients with renal insufficiency (see the sections "Pharmacokinetics" and "Special instructions")

The excretion of perindoprilat in elderly patients and patients with renal insufficiency is slowed. Therefore, in such patients it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

Prestants can be given to patients with creatinine clearance (CC) equal to or greater than 60 ml / min.

Prestanz is contraindicated in patients with SC less than 60 ml / min. (see section "Contraindications"). Such patients are recommended individual selection of doses of perindopril and amlodipine. Amlodipine, used in equivalent doses, is equally tolerated by patients, both elderly and younger patients. It is not necessary to change the dosage regimen in elderly patients, but the dose increase should be carried out with caution, which is associated with age-related changes and an increase in T1/2. The change in the concentration of amlodipine in the blood plasma does not correlate with the degree of renal insufficiency. Amlodipine is not eliminated from the body by dialysis.

Patients with hepatic insufficiency (see the sections "Dosing and Administration" and "Special instructions")

For patients with mild or moderate hepatic insufficiency, dose selection should be performed with caution. It is recommended to start taking the drug from low doses (see sections "Dosing and Administration" and "Special instructions"). The search for an optimal initial and maintenance dose for patients with hepatic insufficiency should be carried out individually, using amlodipine and perindopril preparations in monotherapy. The pharmacokinetics of amlodipine in patients with severe hepatic insufficiency has not been studied. For such patients, amlodipine should be taken at the lowest dose and increased gradually.

Children and teens

Prestants should not be given to children and adolescents under 18 years of age because of the lack of data on the efficacy and safety of perindopril and amlodipine in these groups of patients in the form of combination therapy.

Side effects:

The frequency of adverse reactions that were noted in monotherapy with perindopril and amlodipine is given in the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000,<1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), including individual messages; frequency (frequency can not be calculated from available data).

On the part of the hematopoiesis and lymphatic system Rarely: leukopenia / neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase, a decrease in hemoglobin and hematocrit.

From the immune system Infrequent: allergic reactions.

Metabolic disorders 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, hypoesthesia, depression, faint. Rarely: confusion of consciousness. Rarely: peripheral neuropathy, hypertonus.

From the side of the organ of vision Often: visual impairment (including diplopia).

From the side of the hearing organ Often: noise in ears.

From the side of the cardiovascular system Often: sensation of a palpitation, "tides" of a blood to a skin of the face, expressed depression of a BP. Rarely: angina pectoris, myocardial infarction, possibly due to excess BP reduction in patients at high risk (see section "Special instructions"), arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to excess BP decrease in patients from the high-risk group (see section "Special instructions"), vasculitis.

From the respiratory system Often: shortness of breath, cough. Infrequently: rhinitis, bronchospasm. Rarely: eosinophilic pneumonia.

From the digestive system Often: abdominal pain, nausea, vomiting, indigestion, diarrhea, constipation. Infrequently: change in the rhythm of defecation, dryness of the oral mucosa. Rarely: pancreatitis, gingival hyperplasia, gastritis.

From the liver and biliary tract Rarely: hepatitis, jaundice, increased activity of "hepatic" enzymes (most often - in combination with cholestasis), cytolytic or cholestatic hepatitis (see section "Special instructions").

From the skin and subcutaneous fat Often: skin itching, rash, exanthema. Infrequently: angioedema, swelling of the face, extremities, lips, mucous membranes, tongue, vocal folds and / or larynxsection "Special instructions"), alopecia, hemorrhagic rash, discoloration of the skin, increased sweating, hives. Rarely: Quincke's edema, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, photosensitivity.

From the musculoskeletal system and connective tissue Often: muscle spasms, edema of the shins. Infrequently: arthralgia, myalgia, back pain.

From the side of the kidneys and urinary tract Infrequently: violation of urination, nocturia, frequent urination, violation of the function of the nights. Rarely: acute renal failure.

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

General disorders and symptoms Often: edema, fatigue, increased fatigue. Infrequently: pain in the chest, malaise, pain.

Laboratory indicators Infrequently: weight gain, weight loss. Rarely: increase in bilirubin concentration. Unspecified frequency: an increase in the concentration of urea and creatinine in the blood serum, hyperkalemia (see section "Special instructions").

Additional information on amlodipine:

Individual cases of extrapyramidal syndrome have been reported.

Overdose:

Information about an overdose of Prestans is absent.

Amlodipine

Information about an overdose of amlodipine is limited.

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

Treatment: gastric lavage, the appointment of activated charcoal (especially in the first 2 hours after an overdose), maintenance of cardiovascular function and the respiratory system, elevated limb position, control of bcc and diuresis, symptomatic and supportive therapy, intravenous administration of calcium gluconate and dopamine. Hemodialysis Ineffective. With a significant reduction in blood pressure, a patient should be monitored in a cardiac intensive care unit. In the absence of contraindications to restore the tone of blood vessels and blood pressure, use vasoconstrictors.

Perindopril

Data on perindopril overdose are limited.

Symptoms: a significant reduction in blood pressure, shock, water-electrolyte disorders, renal failure, hyperventilation, tachycardia, sensation heartbeat, bradycardia, dizziness, restlessness and coughing.

Treatment: with a significant decrease in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs, if necessary, correction of hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Intravenous administration of catecholamines is also possible. With the help of hemodialysis can be removed perindopril from the systemic blood flow (see section "Special instructions"). With a bradycardia resistant to therapy, it may be necessary to install an artificial pacemaker. Dynamic control of the physical state, concentration of creatinine and electrolytes of blood plasma is necessary.

Emergency measures are reduced to removing the drug from the body: gastric lavage and / or the appointment of activated charcoal, followed by restoration of the water electrolyte balance.

Interaction:

Perindopril

Unsuitable combinations of drugs

Potassium-sparing diuretics, potassium preparations and potassium-containing substitutes for edible salt: Despite the fact that the potassium content in the blood serum remains within the normal range, in some patients, peripodopril may exhibit hyperkalemia. Potassium-sparing diuretics (for example, spironolactone and its derivative eplerenone, triamterene, amiloride), potassium preparations and potassium-containing substitutes for edible salt can lead to a significant increase in the potassium content in the serum. Therefore, simultaneous use of an ACE inhibitor and the above agents is not recommended (see section "Special instructions"). If simultaneous use is necessary (in case of confirmed hypokalemia), care should be taken and regular monitoring of potassium content in plasma and ECG parameters should be carried out. Lithium preparations: while simultaneous use of lithium drugs and ACE inhibitors, there can be a reversible increase in lithium in the blood plasma and the associated toxic effects. Simultaneous use of perindopril and lithium preparations is not recommended. If this therapy is necessary, regular monitoring of lithium content in blood plasma (see section "Special instructions") is necessary. Estramustine: simultaneous use of estramustine with ACE inhibitors is accompanied by an increased risk of angioedema.

Combinations of medicines requiring special attention

Non-steroidal anti-inflammatory drugs (NSAIDs), include high doses of acetylsalicylic acid (more than 3 g / day): simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose of anti-inflammatory effect, inhibitors of cyclooxygenase-2 (COX-2) and nonselective NSAIDs), can lead to a decrease in the antihypertensive effect of ACE inhibitors. Simultaneous use of ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal failure and an increase in serum potassium blood, especially in patients with impaired renal function. Care should be taken when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and closely monitor kidney function, both at the beginning of treatment and during treatment.

Hypoglycemic agents (hypoglycemic agents for oral administration, sulfonylureas and insulin derivatives): ACE inhibitors can increase the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. Hypoglycaemia occurs very rarely (likely due to the increase in glucose tolerance and reduce insulin requirements).

Combinations of medicines requiring attention

Diuretics (thiazide and "loop"): in patients receiving diuretics, especially with excessive excretion of fluid and / or electrolytes, at the start of therapy with an ACE inhibitor, a significant reduction in blood pressure can be observed, the risk of which can be reduced by eliminating the diuretic, injecting an increased amount of fluid and / or cookery salt, and also appointing perindopril in a low dose with further gradual increase.

Sympathomimetics: can weaken the antihypertensive effect of inhibitors ACE. Preparations of gold: when using inhibitors ACE, including perindopril to patients receiving intravenously a preparation of gold (sodium aurotomy malate), the symptom complex was described, which includes: flushing of the facial skin, nausea, vomiting, arterial hypotension.

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

Means for general anesthesia: simultaneous use of inhibitors ACE and means for general anesthesia can lead to an increase in antihypertensive effect.

Amlodipine

Unsuitable combinations of drugs

Dantrolene (intravenous): In laboratory animals, cases of ventricular fibrillation with a lethal outcome and collapse on the background of verapamil and intravenous dantrolene were observed, accompanied by hyperkalemia. Due to the risk of development hyperkalemia should be avoided simultaneous reception of blockers of "slow" calcium channels, including amlodipine, in patients prone to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

Combinations of medicines requiring special attention

Inductors of cytochrome isoenzymes CYP3A4:

Data on the effect of inducers of isoenzyme CYP3A4 on amlodipine are absent.Simultaneous reception of isoenzyme inducers CYP3A4 (eg, rifampicin, St. John's wort products) can lead to a decrease in plasma concentrations of amlodipine. Caution should be exercised with the simultaneous use of amlodipine and inducers of microsomal oxidation. Inhibitors of cytochrome isoenzymes CYP3A4:

Simultaneous reception of amlodipine and powerful or moderate inhibitors CYP3A4 (protease inhibitors, antifungal agents of the azole group, macrolides, for example, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this connection, it may be necessary to monitor the clinical state and dose adjustment.

Combinations of medicines requiring attention

Amlodipine enhances the antihypertensive effect of drugs with antihypertensive effect.

Other combinations of drugs:

In clinical trials of drug interactions amlodipine ns had an effect on the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine.

Simultaneous reception of amlodipine and the use of grapefruit or grapefruit juice is not recommended, due to the possible increase in the bioavailability of amlodipine in some patients, which in turn can lead to an increase in the effects of lowering blood pressure.

Prestans

Combinations of medicines requiring special attention:

Baclofen: may increase the antihypertensive effect. It is necessary to monitor blood pressure and kidney function, if necessary, correction of amlodipine dose is required.

A combination of drugs that requires attention:

Hypotensive drugs (eg, beta-blockers) and vasodilators: it is possible to increase the antihypertensive effect of perindopril and amlodipine. Caution should be exercised when concomitant administration with nitroglycerin, other nitrates or other vasodilators, as this may further reduce blood pressure.

Corticosteroids (mineral and glucocorticosteroids), tetracosactide: decrease in antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

Alpha-blockers (prazozin, alfuzosin, doxazosin, tamsulosin, terazosin): increased antihypertensive action and increased risk of orthostatic hypotension. Amifostin: it is possible to increase the antihypertensive effect of amlodipine. Tricyclic antidepressants / antipsychotics / general anesthetic agents: increased antihypertensive action and increased risk of orthostatic hypotension.

Special instructions:

Special instructions pertaining to perindopril and amlodipine are also applicable to the preparation of Prestan.

Perindopril

Hypersensitivity / angioedema

When taking ACE inhibitors, including perindopril, in rare cases, development of an angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and / or larynx can be observed (see section "Side effect"). When symptoms appear, taking 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 pass on their own, although antihistamines can be used to treat the symptoms.

Angioedema, accompanied by swelling of the larynx, can lead to death. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. When these symptoms occur, you should immediately enter epinephrine (epinephrine) subcutaneously and / or provide airway patency. The patient should be under medical supervision until the symptoms disappear completely and persistently.

Patients with a history of Quinck's edema who are not associated with taking ACE inhibitors may be at increased risk of developing this drug when taking this drug (see "Contraindications").

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases, without a previous angioedema and at a normal level of C1-esterase. The diagnosis is established using computed tomography of the abdominal region, ultrasound or at the time of surgery. Symptoms disappear after stopping the intake of ACE inhibitors.Therefore, patients with abdominal pain receiving ACE inhibitors should take into account the possibility of angioedema edema development during differential diagnosis (see section "Side effect").

Anaphylactoid reactions during apheresis of LDL

In rare cases, patients who receive ACE inhibitors may experience life-threatening anaphylactoid reactions during low-density lipoprotein (APL) apheresis using dextran sulfate. To prevent anaphylactoid reaction, therapy with an ACE inhibitor should be temporarily discontinued before each apheresis procedure.

Anaphylactoid reactions during desensitization

There are some reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy (for example, the poison of Hymenoptera insects). In the same patients, the anaphylactoid reaction could be avoided by the temporary withdrawal of ACE inhibitors, and if the drug was randomly taken, the anaphylactoid reaction occurred again.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Against the background of the administration of ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia can occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. With extreme caution should be applied perindopril in patients with systemic connective diseases tissue, against the background of the use of immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.

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

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients without concomitant diseases. The risk of excessive reduction in blood pressure is increased in patients with a reduced volume of circulating blood, which can occur with diuretic therapy, while observing a strict salt-free diet, hemodialysis,diarrhea and vomiting, as well as in patients with severe hypertension with high renin activity (see section "Interaction with Other Drugs"). In patients with an increased risk of developing symptomatic arterial hypotension, it is necessary to carefully monitor blood pressure, kidney function and serum potassium content during drug therapy

Prestans

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

In the case of development of arterial hypotension the patient should be transferred to the "lying" position on the back with raised legs. If necessary, replenish the volume of circulating blood by intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle for further administration of the drug. After recovery of the volume of circulating blood and blood pressure, treatment can be continued.

Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

Prestans, like other ACE inhibitors, should be administered with caution to patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral stenosis.

Impaired renal function

Patients with renal insufficiency (CC less than 60 ml / min) are recommended individual selection of doses of perindopril and amlodipine. Such patients need regular monitoring of potassium and creatinine in the blood serum (see section "Side effect").

In patients with bilateral stenosis of the renal artery or stenosis of the artery of a single kidney against the background of therapy with ACE inhibitors, an increase in the concentration of urea and creatinine in the blood serum, usually taking place with the withdrawal of therapy, is possible. More often this effect is observed in patients with renal insufficiency. The additional presence of reninvascular hypertension causes an increased risk of severe arterial hypotension and kidney failure in these patients. In some patients with arterial hypertension without signs of renal vascular disease, an increase in the concentration of urea and creatinine in the serum,especially with the simultaneous administration of perindopril with a diuretic, usually minor and transient. More often this effect is noted in patients with a previous impairment of kidney function.

Liver failure

In rare cases, when 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. When jaundice or a significant increase in the activity of "liver" enzymes against the background of taking ACE inhibitors should stop taking the drug (see section "Side effect").

Ethnic differences

In patients of the Negroid race, angioneurotic edema develops more often than in representatives of other races against the background of the administration of ACE inhibitors.

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

Cough

Against the background of therapy with an ACE inhibitor, dry cough may occur. Cough persists for a long time against the background of taking this group's drugs and disappears after their withdrawal. When a patient has a dry cough, remember the possible iatrogenic nature of this symptom.

Surgery / general anesthesia

The use of ACE inhibitors in patients undergoing extensive surgery and / or general anesthesia can lead to a marked decrease in blood pressure if general anesthetics with hypotensive action are used. This is due to blocking the formation of angiotensin II against a background of compensatory enhancement of renin activity. If the development of arterial hypotension is associated with the described mechanism, you should increase the volume of circulating plasma. It is recommended to alert the surgeon / anesthesiologist that the patient is taking ACE inhibitors and stop taking the drug 24 hours before surgery.

Hyperkalemia

Hyperkalemia can develop during treatment with ACE inhibitors, including, and perindopril. Risk factors for hyperkalemia are renal failure, age over 70 years, diabetes,Some concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), simultaneous reception of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing substitutes cookery salts, as well as the use of other drugs that increase the potassium content in the blood plasma (for example, heparin). The use of potassium, 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 simultaneous administration of perindopril and the above drugs is required, treatment should be carried out with caution in the context of regular monitoring of potassium in the blood serum (see section "Interaction with other medicinal products").

Patients with diabetes mellitus

When the drug is prescribed for patients with diabetes mellitus, who receive hypoglycemic agents for ingestion or insulin,During the first month of therapy, the concentration of glucose in the blood should be carefully monitored (see section "Interaction with other medicinal products").

Amlodipine

The efficacy and safety of the use of amlodipine in hypertensive crisis is not established.

Heart failure

Treatment of patients with heart failure should be done with caution. When using amlodipine in patients with chronic heart failure III and IV functional class by classification NYHA possibly the development of pulmonary edema. Blocks of "slow" calcium channels, including amlodipine, should be used with caution in patients with chronic heart failure, due to the possible increase in the risk of development of adverse events from the cardiovascular system and mortality.

Liver failure

In patients with impaired hepatic function T1/2 and AUC Amlodipine increases. Admission of amlodipine should start with the lowest doses and observe precautions, both at the beginning of treatment, and also with increasing doses. Patients with severe hepatic insufficiency should increase the dose gradually,ensuring a thorough monitoring of the clinical condition.

Elderly patients

In elderly patients may increase T1 / 2 and decrease the clearance of amlodipine. Dose changes are not required, but more careful monitoring of patients of this category is necessary.

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

Renal insufficiency

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

Prestans

Excipients

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

Effect on the ability to drive transp. cf. and fur:

Although there was no adverse effect on the ability to drive motor vehicles or other complex mechanisms against the background of taking Prestans, however, due to the possible excessive decrease in blood pressure, the development of dizziness, drowsiness and other adverse reactions,Care should be taken in these situations, especially at the beginning of treatment and with increasing doses.

Form release / dosage:

Tablets containing 5 mg perindopril arginine + 5 mg amlodipine, 10 mg perindopril arginine + 10 mg amlodipine, 5 mg perindopril arginine + 10 mg amlodipine, 10 mg perindopril arginine + 5 mg amlodipine.

Packaging:

In production:

1. "Servier Industrials", France

2. Servier (Ireland) Industries Ltd., Ireland

30 tablets in a polypropylene bottle, equipped with a dispenser and a stopper containing a moisture-absorbing gel (silica gel).

1 bottle with instructions for medical use in a pack of cardboard with the control of the first autopsy.

When packaging (packaging) / production: LLC "Serdiks", Russia

30 tablets per bottle of polypropylene. equipped with a dispenser and a stopper containing a moisture absorbing gel (silica gel).

1 bottle with instructions for medical use in a pack of cardboard with the control of the first autopsy.

Packing for hospitals:

30 tablets per bottle of polypropylene. equipped with a dispenser and a stopper containing a moisture absorbing gel.

For 30 bottles in a cardboard pallet with vial cells, with an equal number of instructions for medical use in a carton box with the control of the first autopsy. For 3 bottles with an equal number of instructions for medical use in a pack of cardboard with the control of the first autopsy.

Storage conditions:

Special storage conditions are not required.

Keep the bottle tightly closed. Keep in original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

DO NOT USE AT THE EXPIRY OF THE YEAR OF LIFE, INDICATED ON PACKAGING.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000836/10

Date of registration:09.02.2010

The owner of the registration certificate:Servier LaboratoriesServier Laboratories France

Manufacturer: & nbsp

Les Laboratoires Servier Industrie France

Representation: & nbspServier Laboratories Servier Laboratories France

Information update date: & nbsp13.01.2015

Illustrated instructions

Instructions

Prestans (Prestance®)